Archive for October, 2020

Acute Lymphoblastic Leukemia (AML), also called acute myeloblastic leukemia, acute myelogenous leukemia, acute myeloid leukemia, or acute nonlymphocytic leukemia, is an aggressive, fast-growing, heterogenous group of blood cancers that arise as a result of clonal expansion of myeloid hematopoietic precursors in the bone marrow. Not only are circulating leukemia (blast) cells seen in the peripheral blood, but granulocytopenia, anemia, and thrombocytopenia are also common as proliferating leukemia cells interfere with normal hematopoiesis.

Approximately 40-45% of younger and 10-20% of older adults diagnosed with AML are cured with current standard chemotherapy. However, the outlook for patients with relapsed and/or refractory disease is gloomy. Relapse following conventional chemotherapy remains is a major cause of death.

The process of manufacturing chimeric antigen receptor (CAR) T-cell therapies. [1] T-cells (represented by objects labeled as t) are removed from the patients blood. [2] Then in a lab setting the gene that encodes for the specific antigen receptors is incorporated into the T-cells. [3] Thus producing the CAR receptors (labeled as c) on the surface of the cells. [4] The newly modified T-cells are then further harvested and grown in the lab. [5]. After a certain time period, the engineered T-cells are infused back into the patient. This file is licensed by Reyasingh56 under the Creative Commons Attribution-Share Alike 4.0 International license.Today, the only curative treatment option for patients with AML is allogeneic hematopoietic stem cell transplantation or allo-HSCT, which through its graft-vs.-leukemia effects has the ability to eliminate residual leukemia cells. But it is an ption for only a minority. And despite a long history of success, relapse following allo-HSCT is still a major challenge and is associated with poor prognosis.

In recent years, rresearchers learned a lot about the genomic and epigenomic landscapes of AML. This understanding has paved the way for rational drug development as new drugable targets, resulting in treatments including the antibody-drug conjugate (ADC) gemtuzumab ozogamycin (Mylotarg; Pfizer/Wyeth-Ayerst Laboratories).

CAR T-cell TherapiesChimeric antigen receptor (CAR) T-cells therapies, using a patients own genetically modified T-cells to find and kill cancer, are one of the most exciting recent developments in cancer research and treatment.

Traditional CAR T-cell therapies are an autologous, highly personalised, approach in which T-cells are collected from the patient by leukopheresis and engineered in the laboratory to express a receptor directed at a cancer antigen such as CD19. The cells are then infused back into the patient after administration of a lymphodepletion regimen, most commonly a combination of fludarabine and cyclophosphamide. Durable remissions have been observed in pediatric patients with B-ALL and adults with NHL.

CD19-targeted CAR T-cell therapies, have, over the last decade, yielded remarkable clinical success in certain types of B-cell malignancies, and researchers have made substantial efforts aimed at translating this success to myeloid malignancies.

While complete ablation of CD19-expressing B cells, both cancerous and healthy, is clinically tolerated, the primary challenge limiting the use of CAR T-cells in myeloid malignancies is the absence of a dispensable antigen, as myeloid antigens are often co-expressed on normal hematopoietic stem/progenitor cells (HSPCs), depletion of which would lead to intolerable myeloablation.

A different approachBecause autologous CAR T-cell therapies are patient-specific, each treatment can only be used for that one patient. Furthermore, because CAR T-cells are derived from a single disease-specific antibody, they are, by design, only recognized by one specific antigen. As a consequence, only a small subset of patients with any given cancer may be suited for the treatment.

This specificity means that following leukopheresis, a lot of work needs to be done to create this hyper personalised treatment option, resulting in 3 5 weeks of manufacturing time.

The manufacturing process of CAR T-cell therapies, from a single academic center to a large-scale multi-site manufacturing center further creates challenges. Scaling out production means developing processes consistent across many collection, manufacturing, and treatment sites. This complexity results in a the realitively high cost of currently available CAR T-cell therapies.

To solve some of the concerns with currently available CAR T-cell therapies, researchers are investigating the option to develop allogenic, off-the-shelf Universal CAR T-cell (UCARTs) treatments that can be mass manufactured and be used for multiple patients.

Allogeneic CAR T-cell therapy are generally created from T-cells from healthy donors, not patients. Similar to the autologous approach, donor-derived cells are shipped to a manufacturing facility to be genetically engineered to express the antibody or CAR, however, in contrast to autologous CAR T-cells, allogeneic CAR T-cells are also engineered with an additional technology used to limit the potential for a graft versus host reaction when administered to patients different from the donor.

One unique benefit ofn this approach is that because these therapies hey are premade and available for infusion, there is no requirement to leukopheresis or a need to wait for the CAR T-cells to be manufactured. This strategy also will benefit patients who are cytopenic (which is not an uncommon scenario for leukemia patients) and from whom autologous T-cell collection is not possible.

PioneersAmong the pioneers of developing allogeneic CAR-T therapies are companies including Celyad Oncology, Cellectis, Allogene Therapeutics, and researchers at University of California, Los Angeles (UCLA) in colaboration with Kite/Gilead.

Researchers at UCLA were, for example, able to turn pluripotent stem cells into T-cells through structures called artificial thymic organoids. These organoids mimic the thymus, the organ where T-cells are made from blood stem cells in the body.

Celyad OncologyBelgium-based Celyad Oncology is advancing a number of both autologous and allogeneic CAR T-cell therapies, including proprietary, non-gene edited allogeneic CAR T-cell candidates underpinned by the companys shRNA technology platform. The shRNA platform coupled with Celyads all-in-one vector approach provides flexibility, versatility, and efficiency to the design of novel, off-the-shelf CAR T-cell candidates through a single step engineering process.

In July 2020, the company announced the start of Phase I trials with CYAD-211, Celyads first-in-class short hairpin RNA (shRNA)-based allogeneic CAR T candidate and second non-gene edited off-the-shelf program. CYAD-211 targets B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma and is engineered to co-express a BCMA-targeting chimeric antigen receptor and a single shRNA, which interferes with the expression of the CD3 component of the T-cell receptor (TCR) complex.

During the 2020 American Society of Clinical Oncology (ASCO) Virtual Scientific Program in May 2020, the company presented updates from its allogeneic programs, including additional data from the alloSHRINK study, an open-label, dose-escalation Phase I trial assessing the safety and clinical activity of three consecutive administrations of CYAD-101, an investigational, non-gene edited, allogeneic CAR T-cell candidate engineered to co-express a chimeric antigen receptor based on NKG2D (a receptor expressed on natural killer (NK) cells that binds to eight stress-induced ligands and the novel inhibitory peptide TIM TCR Inhibitory Molecule), for the treatment of metastatic colorectal cancer (mCRC).

The expression of TIM reduces signalling of the TCR complex, which is responsible for graft-versus host disease.every two weeks administered concurrently with FOLFOX (combination of 5-fluorouracil, leucovorin and oxaliplatin) in patients with refractory metastatic colorectal cancer (mCRC).

The safety and clinical activity data from the alloSHRINK trial in patients with mCRC demonstrated CYAD-101s differentiated profile as an allogeneic CAR T-cell candidate. Furthermore, the absence of clinical evidence of graft-versus-host-disease (GvHD) for CYAD-101 confirms the potential of non-gene edited approaches for the development of allogeneic CAR-T candidates.

Interim data from the alloSHRINK trial showed encouraging anti-tumor activity, with two patients achieving a confirmed partial response (cPR) according to RECIST 1.1 criteria, including one patient with a KRAS-mutation, the most common oncogenic alteration found in all human cancers. In addition, nine patients achieved stable disease (SD), with seven patients demonstrating disease stabilization lasting more than or equal to three months of duration.

Based on these results, clinical trials were broadened to include evaluating CYAD-101 following FOLFIRI (combination of 5-fluorouracil, leucovorin and irinotecan) preconditioning chemotherapy in refractory mCRC patients, at the recommended dose of one billion cells per infusion as an expansion cohort of the alloSHRINK trial. Enrollment in the expansion cohort of the trial is expected to begin during the fourth quarter of 2020.

CellectisCellectis is developping a universal CAR T-cell (UCART) platform in an attempy to create off-the-shelf CAR T-cell therapies. The companys pipeline includes UCART123, a CAR T-cell therapy designed to targets CD123+ leukemic cells in acute myeloid leukemia (AML). The investigational agent is being studied in two open-label Phase I trials: AML123 studying the therapys safety and efficacy in an estimated 156 AML patients, and ABC123 studying the therapys safety and activity in an estimated 72 patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

UCART22Another investigational agent in clinical trials is UCART22 which is designed to treat both CD22+ B-cell acute lymphoblastic leukemia (B-ALL) and CD22+ B-cell non-Hodgkin lymphoma (NHL). Cellectis reported that UCART22 is included in an open-label, dose-escalating Phase I trial to study its safety and activity in relapsed or refractory CD22+ B-ALL patients.

UCART22 harbors a surface expression of an anti-CD22 CAR (CD22 scFv-41BB-CD3z) and the RQR8 ligand, a safety feature rendering the T-cells sensitive to the antibody rituximab. Further, to reduce the potential for alloreactivity, the cell surface expression of the T-cell receptor is abrogated through the inactivation of the TCR constant (TRAC) gene using Cellectis TALEN gene-editing technology.[1]

Preclinical data supporting the development of UCART22 was presented by Marina Konopleva, M.D., Ph.D. and her vteam during the 2017 annual meeting of the American Society of Hematology (ASH) meeting. [1]

Cellectis is also developing UCARTCS1 which is developed to treat CS1-expressing hematologic malignancies, such as multiple myeloma (MM). UCARTCLL1 is in preclinical development for treating CLL1-expressing hematologic malignancies, such as AML.

Cellectis and Allogene Therapeutics, another biotech company involved in the developmen t of CAR T-cell therapies, are developing ALLO-501, another CAR T-cell therapy which targets CD19 and is being developed for the the treatment of patients with relapsed or refractory NHL. Allogene Therapeutics is also developing ALLO-715, an investigational CAR T-cell therapy targeting the B-cell maturation antigen (BCMA) for treating relapsed or refractory multiple myeloma and ALLO-819, which targets CD135 (also called FLT3), for treating relapsed or refractory AML.

Allogene, in collaboration with both Cellectis, Pfizer (which has a 25% stake in Allogene) and Servier have numerous active open-label, single-arm Phase I trials for an off-the-shelf allogeneic CAR-T therapy UCART19* in patients with relapsed or refractory CD19+ B-ALL. Participating patients receive lymphodepletion with fludarabine and cyclophosphamide with alemtuzumab, followed by UCART19 infusion. Adults patients with R/R B-ALL are eligible.

The PALL aims to evaluate the safety and feasibility of UCART19 to induce molecular remission in pediatric patients with relapsed or refractory CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) in 18 pediatric patients.

The CALM trial is a dose-escalating study evaluating the therapys safety and tolerability in 40 adult patients; and a long-term safety and efficacy follow-up study in 200 patients with advanced lymphoid malignancies.

Allogene reported preliminary proof-of-concept results during the annual meeting of the American Society of Hematology (ASH) in December 2018.

Data from the first 21 patients from both the PALL (n=7) and CALM (n=14) Phase I studies were pooled. The median age of the participating patients was 22 years (range, 0.8-62 years) and the median number of prior therapies was 4 (range, 1-6). Sixty-two percent of the patients (13/21) had a prior allogeneic stem cell transplant.

Of the 17 patients who received treatment with UCART19 and who received lymphodepletion with fludarabine, cyclophosphamide and alemtuzumab, an anti-CD52 monoclonal antibody, 14 patients (82%) achieved CR/CRi, and 59% of them (10/17) achieved MRD-negative remission.

In stark contrast, the four patients who only received UCART19 and fludarabine and cyclophosphamide without alemtuzumab did not see a response and minimal UCART19 expansion.

Based on these results, researchers noted that apparent importance of an anti-CD52 antibody for the efficacy of allogeneic CAR-T therapies. In addition, safety data also looked promising. The trial results did not include grade 3 or 4 neurotoxicity and only 2 cases of grade 1 graft-versus-host disease (10%), 3 cases of grade 3 or 4 cytokine release syndrome which were considered manageable (14%), 5 cases of grade 3 or 4 viral infections (24%), and 6 cases of grade 4 prolonged cytopenia (29%).

Precision BiosciencesPrecision Biosciences is developing PBCAR0191, an off-the-shelf investigational allogeneic CAR T-cell candidate targeting CD19. The drug candidate is being investigated in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study for the treatment of patients with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or R/R B-cell precursor acute lymphoblastic leukemia (B-ALL).

The NHL cohort includes patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision has received both Orphan Drug and Fast Track Designations from the U.S. Food and Drug Administration (FDA).

A clinical trial with PBCAR0191 Precision Biosciences is exploring some novel lymphodepletion strategies in addition to fludarabine and cyclophosphamide. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well. This trial is enrolling patients.

In late September 2020, Precision BioSciences, a clinical stage biotechnology amd Servier, announced the companies have added two additional hematological cancer targets beyond CD19 and two solid tumor targets to its CAR T-cell development and commercial license agreement.

PBCAR20APBCAR20A is an investigational allogeneic anti-CD20 CAR T-cell therapy being developed by Precision Biosciences for the treartment of patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) and patients with R/R chronic lymphocytic leukemia (CLL) or R/R small lymphocytic lymphoma (SLL). The NHL cohort will include patients with mantle cell lymphoma (MCL), an aggressive subtype of NHL, for which Precision BioSciences has received orphan drug designation from the United States Food and Drug Administration (FDA).

PBCAR20A is being evaluated in a Phase I/IIa multicenter, nonrandomized, open-label, dose-escalation and dose-expansion clinical trial in adult NHL and CLL/SLL patients. The trial will be conducted at multiple U.S. sites.

PBCAR269APrecision Biosciences is, in collaboration with Springworks Therapeutics, also developing PBCAR269A, an allogeneic BCMA-targeted CAR T-cell therapy candidate being evaluated for the safety and preliminary clinical activity in a Phase I/IIa multicenter, nonrandomized, open-label, parallel assignment, single-dose, dose-escalation, and dose-expansion study of adults with relapsed or refractory multiple myeloma. In this trial, the starting dose of PBCAR269A is 6 x 105 CAR T cells/kg body weight with subsequent cohorts receiving escalating doses to a maximum dose of 6 x 106 CAR T cells/kg body weight.

PBCAR269A is Precision Biosciencess third CAR T-cell candidate to advance to the clinic and is part of a pipeline of cell-phenotype optimized allogeneic CAR T-cell therapies derived from healthy donors and then modified via a simultaneous TCR knock-out and CAR T-cell knock-in step with the =companys proprietary ARCUS genome editing technology.

The FDA recently granted Fast Track Designation to PBCAR269A for the treatment of relapsed or refractory multiple myeloma for which the FDA previously granted Orphan Drug Designation.

TCR2 TherapeuticsTCR2 Therapeutics is developing a proprietary TRuC (TCR Fusion Construct) T-cells designed to harness the natural T cell receptor complex to recognize and kill cancer cells using the full power of T-cell signaling pathways independent of the human leukocyte antigen (HLA).

While succesful in hematological malignancies, CAR T-cells therapies have generally struggled to show efficacy against solid tumors. Researchers at TCR2 Therapeutics believe this is is caused by the fact that CAR T-cell therapies only utilize a single TCR subunit, and, as a result, do not benefit from all of the activation and regulatory elements of the natural TCR complex. By engineering TCR T-cells, which are designed to utilize the complete TCR, they have demonstrated clinical activity in solid tumors. However, this approach has also shown major limitations. TCR T-cells require tumors to express HLA to bind tumor antigens. HLA is often downregulated in cancers, preventing T-cell detection. In addition, each specific TCR-T cell therapy can only be used in patients with one of several specific HLA subtypes, limiting universal applicability of this approach and increasing the time and cost of patient enrollment in clinical trials.

In an attempt to solve this problem, researchers at TCR2 Therapeutics have developped a proprieatarry TRuC-T Cells which are designed to incorporate the best features of CAR-T and TCR-T cell therapies and overcome the limitations. The TRuC platform is a novel T cell therapy platform, which uses the complete TCR complex without the need for HLA matching.

By conjugating the tumor antigen binder to the TCR complex, the TRuC construct recognizes highly expressed surface antigens on tumor cells without the need for HLA and engage the complete TCR machinery to drive the totality of T-cell functions required for potent, modulated and durable tumor killing.

In preclinical studies, TCR2 Therapeutics TRuC T-cells technology has demonstrated superior anti-tumor activity in vivo compared to CAR T-cells therapies, while, at the same time, releasing lower levels of cytokines. These data are encouraging for the treatment of solid tumors where CAR T-cells have not shown significant clinical activity due to very short persistence and for hematologic tumors where a high incidence of severe cytokine release syndrome remains a major concern.

TCR2 Therapeutics product candidates include TC-210 and TC-110.

TC-210 is designed to targets mesothelin-positive solid tumors. While its expression in normal tissues is low, mesothelin is highly expressed in many solid tumors. Mesothelin overexpression has also been correlated with poorer prognosis in certain cancer types and plays a role in tumorigenesis. TC-210 is being developed for the treatment of non-small cell lung cancer, ovarian cancer, malignant pleural/peritoneal mesothelioma and cholangiocarcinoma.

The companys TRuC-T cell targeting CD19-positive B-cell hematological malignancies, TC-110, is being developed to improve upon and address the unmet needs of current CD19-directed CAR T-cell therapies. The clinical development TC-110 focus on the treatment of adult acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Preclinical data demonstrates that TC-110 is superior to CD19-CAR-T cells (carrying either 4-1BB or CD28 co-stimulatory domains) both in anti-tumor activity as well as the level of cytokine release which may translate into lower rates of adverse events. The development of TC-110 starts with autologous T-cells collection by leukopheresis. These T-cells undergo genetic engineering to create TRuC-T cells targeting CD19.

This strategy combines the best features of CAR T-cells and the native T-cell receptor. It is open for R/R NHL and R/R B-ALL.

AUTO1Auto1 is an autologous CD19 CAR T-cell investigational therapyis being developped by Autolus Therapeutics. The investigational drug uses a single-chain variable fragment (scFv) called CAT with a lower affinity for CD19 and a faster off-rate compared to the FMC63 scFv used in other approved CD19 CAR T-cell therapies. The investigational therapy is designed to overcome the limitations in safety while maintaining similar levels of efficacy compared to current CD19 CAR T-cell therapies.

Designed to have a fast target binding off-rate to minimize excessive activation of the programmed T-cells, AUTO1 may reduce toxicity and be less prone to T-cell exhaustion, which could enhance persistence and improve the T-cells abilities to engage in serial killing of target cancer cells.

In 2018, Autolus signed a license agreement UCL Business plc (UCLB), the technology-transfer company of UCL, to develop and commercialize AUTO1 for the treatment of B cell malignancies. AUTO1 is currently being evaluated in two Phase I studies, one in pediatric ALL and one in adult ALL.

CARPALL trialInitial results from the ongoing Phase I CARPALL trial of AUTO1 were presented during European Hematology Association 1st European CAR T Cell Meeting held in Paris, France, February 14-16, 2019.

Enrolled patients had a median age of 9 years with a median of 4 lines of prior treatment. Seventeen patients were enrolled, and 14 patients received an infusion of CAR T cells. Ten of 14 patients had relapsed post allogeneic stem cell transplant. Eight patients were treated in second relapse, 5 in > second relapse and 3 had relapsed after prior blinatumomab or inotuzumab therapy. Two patients had ongoing CNS disease at enrollment.

This data confirmed that AUTO1 did not induces severe cytokine release syndrome (CRS) (Grade 3-5). Nine patients experienced Grade 1 CRS, and 4 patients experienced Grade 2 CRS. No patients required tociluzumab or steroids. As previously reported, one patient experienced Grade 4 neurotoxicity; there were no other reports of severe neurotoxicity (Grade 3-5). The mean cumulative exposure to AUTO1 CAR T-cells in the first 28 days as assessed by AUC was 1,721,355 copies/g DNA. Eleven patients experienced cytopenia that was not resolved by day 28 or recurring after day 28: 3 patients Grades 1-3 and 8 patients Grade 4. Two patients developed significant infections, and 1 patient died from sepsis while in molecular complete response (CR).

With a single dose of CAR T cells at 1 million cells/kg dose, 12/14 (86%) achieved molecular CR. Five patients relapsed with CD19 negative disease. Event free survival (EFS) based on morphological relapse was 67% (CI 34-86%) and 46% (CI 16-72%) and overall survival (OS) was 84% (CI 50-96%) and 63% (CI 27-85%) at 6 and 12 months, respectively.

CAR T cell expansion was observed in all responding patients (N=12), with CAR T cells comprising up to 84% of circulating T cells at the point of maximal expansion. The median persistence of CAR T-cells was 215 days.

The median duration of remission in responding patients was 7.3 months with a median follow-up of 14 months. Five of 14 patients (37%) remain in CR with ongoing persistence of CAR T-cells and associated B cell aplasia.

Fate TherapeuticsFT819 is an off-the-shelf CAR T-cell therapy targeting CD19 being developed by Fate Therapeutics. The T-cells are derived from a clonal engineered master induced pluripotent stem cell line (iPSCs) with a novel 1XX CAR targeting CD19 inserted into the T-cell receptor alpha constant (TRAC) locus and edited for elimination of T-cell receptor (TCR) expression.

Patients participating in the companys clinbical trial will receive lymphodepletion with fludarabine and cyclophosphamide. Some patients will also receive IL-2. Patients with R/R ALL, R/R CLL, R/R Richter transformation, and R/R NHL are eligible. Patients with MRD+ B-ALL are eligible as well.

At the Annual Meeting of the American Societ of Hematology held in December 2019, researchers from Fate Therapeutics presented new in vivo preclinical data demonstrating that FT819 exhibits durable tumor control and extended survival. In a stringent xenograft model of disseminated lymphoblastic leukemia, FT819 demonstrated enhanced tumor clearance and control of leukemia as compared to primary CAR19 T-cells. At Day 35 following administration, a bone marrow assessment showed that FT819 persisted and continued to demonstrate tumor clearance, whereas primary CAR T cells, while persisting, were not able to control tumor growth. [2]

CAR-NK CD19Allogeneic cord blood-derived Natural Killer (NK) cells are another off-the-shelf product that does not require the collection of cells from each patient.

Unlike T-cells, NK-cells do not cause GVHD and can be given safely in the allogeneic setting. At MD Anderson Cancer Center, Katy Rezvani, M.D., Ph.D, Professor, Stem Cell Transplantation and Cellular Therapy, and her team broadly focuses their research on the role of natural killer (NK) cells in mediating protection against hematologic malignancies and solid tumors and strategies to enhance killing function against various cancer.

As part of their research, the team has developed a novel cord blood-derived NK-CAR product that expresses a CAR against CD19; ectopically produces IL-15 to support NK-cell proliferation and persistence in vivo; and expresses a suicide gene, inducible caspase 9, to address any potential safety concerns.

In this phase I and II trial researchers administered HLA-mismatched anti-CD19 CAR-NK cells derived from cord blood to 11 patients with relapsed or refractory CD19-positive cancers (non-Hodgkins lymphoma or chronic lymphocytic leukemia [CLL]). NK cells were transduced with a retroviral vector expressing genes that encode anti-CD19 CAR, interleukin-15, and inducible caspase 9 as a safety switch. The cells were expanded ex vivo and administered in a single infusion at one of three doses (1105, 1106, or 1107 CAR-NK cells per kilogram of body weight) after lymphodepleting chemotherapy. The preliminarry resilts of the trials confirmed that administration of CAR-NK cells was not associated with the development of cytokine release syndrome, neurotoxicity, or graft-versus-host disease, and there was no increase in the levels of inflammatory cytokines, including interleukin-6, over baseline.

The study results also demonstrated that of the 11 patients who were treated, 8 patients (73%) had a response. Of these patients, 7 (4 with lymphoma and 3 with CLL) had a complete remission ICR), and 1 had remission of the Richters transformation component but had persistent CLL. Noteworthy was that responses were rapid and seen within 30 days after infusion at all dose levels. The infused CAR-NK cells expanded and persisted at low levels for at least 12 months. The researchers also noted that a majority of the 11 participating patients with relapsed or refractory CD19-positive cancers had a response to treatment with CAR-NK cells without the development of major toxic effects.[3]

Note* Servier will hold ex-US commercial rights. Servier is the sponsor of the UCART19 trials.

Clinical trialsalloSHRINK Standard cHemotherapy Regimen and Immunotherapy With Allogeneic NKG2D-based CYAD-101 Chimeric Antigen Receptor T-cells NCT03692429Study Evaluating Safety and Efficacy of UCART123 in Patients With Relapsed/ Refractory Acute Myeloid Leukemia (AMELI-01) NCT03190278Study to Evaluate the Safety and Clinical Activity of UCART123 in Patients With BPDCN (ABC123) NCT03203369Study of UCART19 in Pediatric Patients With Relapsed/Refractory B Acute Lymphoblastic Leukemia (PALL) NCT02808442Dose Escalation Study of UCART19 in Adult Patients With Relapsed / Refractory B-cell Acute Lymphoblastic Leukaemia (CALM) NCT02746952Dose-escalation Study of Safety of PBCAR0191 in Patients With r/r NHL and r/r B-cell ALL NCT03666000.Dose-escalation Study of Safety of PBCAR20A in Subjects With r/r NHL or r/r CLL/SLL NCT04030195A Dose-escalation Study to Evaluate the Safety and Clinical Activity of PBCAR269A in Study Participants With Relapsed/Refractory Multiple Myeloma NCT04171843TC-110 T Cells in Adults With Relapsed or Refractory Non-Hodgkin Lymphoma or Acute Lymphoblastic Leukemia NCT04323657Phase 1/2 Trial of TC-210 T Cells in Patients With Advanced Mesothelin-Expressing Cancer NCT03907852CARPALL: Immunotherapy With CD19 CAR T-cells for CD19+ Haematological Malignancies NCT02443831Umbilical & Cord Blood (CB) Derived CAR-Engineered NK Cells for B Lymphoid Malignancies NCT03056339

Reference[1] Petti F. Broadening the Applicability of CAR-T Immunotherapy to Treat the Untreatable. OncoZine. October 24, 2019 [Article][2] Wells J, Cai T, Schiffer-Manniou C, Filipe S, Gouble A, Galetto R, Jain N, Jabbour EJ, Smith J, Konopleva M. Pre-Clinical Activity of Allogeneic Anti-CD22 CAR-T Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia Blood (2017) 130 (Supplement 1): 808. https://doi.org/10.1182/blood.V130.Suppl_1.808.808%5B3%5D Chang C, Van Der Stegen S, Mili M, Clarke R, Lai YS, Witty A, Lindenbergh P, Yang BH, et al. FT819: Translation of Off-the-Shelf TCR-Less Trac-1XX CAR-T Cells in Support of First-of-Kind Phase I Clinical Trial. Blood (2019) 134 (Supplement_1): 4434.https://doi.org/10.1182/blood-2019-130584%5B4%5D Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P, Basar R, Nassif Kerbauy L, Overman B, Thall P, Kaplan M, Nandivada V, Kaur I, Nunez Cortes A, Cao K, Daher M, Hosing C, Cohen EN, Kebriaei P, Mehta R, Neelapu S, Nieto Y, Wang M, Wierda W, Keating M, Champlin R, Shpall EJ, Rezvani K. Use of CAR-Transduced Natural Killer Cells in CD19-Positive Lymphoid Tumors. N Engl J Med. 2020 Feb 6;382(6):545-553. doi: 10.1056/NEJMoa1910607. PMID: 32023374; PMCID: PMC7101242.

Featured image: T-cells attacking a cancer cell. Photo courtesy: Fotolia/Adobe 2016 2020. Used with permission.

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CAR T-cell Therapies for the Treatment of Patients with Acute Lymphoblastic Leukemia - OncoZine

BrainStorm Cell Therapeutics Inc. (NASDAQ: BCLI), a leading developer of cellular therapies for neurodegenerative diseases, announced today financial results for the third quarter ended September 30, 2020, and provided a corporate update.

"The most important near-term event for BrainStorm will be the upcoming top-line data readout for the NurOwn Phase 3 trial in ALS, expected by the end of November. A successful outcome will set us on the path to filing a Biologic License Application (BLA) for what we believe will be a valuable new treatment for ALS," said Chaim Lebovits, Chief Executive Officer of BrainStorm Cell Therapeutics. "In parallel to our preparations for upcoming data read out, we are very busy planning and executing on other pre-BLA activities. On the management front, we appointed William K. White and Dr. Anthony Waclawski, adding valuable commercial and regulatory expertise to our leadership team. This expertise will be crucial as we work towards obtaining regulatory approval for NurOwn and ensuring that, if approved, it will be readily accessible to ALS patients in need of new treatment options for this devastating disease."

NurOwn has an innovative mechanism of action that is broadly applicable across neurodegenerative diseases and BrainStorm continues to invest in clinical trials evaluating the product in conditions beyond ALS to maximize value creation for its various stakeholders. The company remains on track to complete dosing in its Phase 2 clinical trial in progressive multiple sclerosis (PMS) by the end of 2020. In addition, the Company recently unveiled a clinical development program in Alzheimer's' disease (AD) and is planning a Phase 2 proof-of-concept clinical trial at several leading AD centers in the Netherlands and France.

Third Quarter 2020 and Recent Corporate Highlights:

Presented at the following Investor Conferences:

Cash and Liquidity as of October 14, 2020

Total available funding as of October 14, 2020, which includes cash, cash equivalents and short-term bank deposits of approximately $33.1 million as well as remaining non-dilutive funding from CIRM, IIA and other grants, amounts to approximately $36 million.

Financial Results for the Three Months Ended September 30, 2020

About NurOwn

NurOwn (autologous MSC-NTF) cells represent a promising investigational therapeutic approach to targeting disease pathways important in neurodegenerative disorders. MSC-NTF cells are produced from autologous, bone marrow-derived mesenchymal stem cells (MSCs) that have been expanded and differentiated ex vivo. MSCs are converted into MSC-NTF cells by growing them under patented conditions that induce the cells to secrete high levels of neurotrophic factors (NTFs). Autologous MSC-NTF cells can effectively deliver multiple NTFs and immunomodulatory cytokines directly to the site of damage to elicit a desired biological effect and ultimately slow or stabilize disease progression. BrainStorm has fully enrolled a Phase 3 pivotal trial of autologous MSC-NTF cells for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm also recently received acceptance from the U.S. Food and Drug Administration (FDA) to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS) and completed enrollment in August 2020.

About BrainStorm Cell Therapeutics Inc.

BrainStorm Cell Therapeutics Inc. is a leading developer of innovative autologous adult stem cell therapeutics for debilitating neurodegenerative diseases. The Company holds the rights to clinical development and commercialization of the NurOwn technology platform used to produce autologous MSC-NTF cells through an exclusive, worldwide licensing agreement. Autologous MSC-NTF cells have received Orphan Drug status designation from the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of amyotrophic lateral sclerosis (ALS). BrainStorm has fully enrolled a Phase 3 pivotal trial in ALS (NCT03280056), investigating repeat-administration of autologous MSC-NTF cells at six U.S. sites supported by a grant from the California Institute for Regenerative Medicine (CIRM CLIN2-0989). The pivotal study is intended to support a filing for U.S. FDA approval of autologous MSC-NTF cells in ALS. BrainStorm also recently received U.S. FDA clearance to initiate a Phase 2 open-label multicenter trial in progressive multiple sclerosis (MS). The Phase 2 study of autologous MSC-NTF cells in patients with progressive MS (NCT03799718) completed enrollment in August 2020. For more information, visit the company's website at http://www.brainstorm-cell.com.

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BrainStorm Announces Financial Results for the Third Quarter 2020 - Citybizlist

An international team of scientists from China, Taiwan and the United States has successfully sequenced and analyzed the genomes of the Chinese banyan tree (Ficus microcarpa), which is famous for its extraordinary aerial roots; Ficus hispida, a related fig species lacking aerial roots; and Eupristina verticillata, a wasp coevolving with the banyan tree. Theyve identified regions in the banyan trees genome that promote the development of its unusual aerial roots and enhance its ability to signal its wasp pollinator, and found a sex-determining region in Ficus hispida.

Zhang et al. reveal the genomic changes that allow the Chinese banyan tree (Ficus microcarpa) to produce roots that spring from its branches. Image credit: Gang Wang.

Understanding the evolutionary history of Ficus species and their wasp pollinators is important because their ability to produce large fruits in a variety of habitats makes them a keystone species in most tropical forests, said Professor Ray Ming, a researcher at the University of Illinois, Urbana-Champaign.

To better understand their evolutionary developments, Professor Ming and colleagues analyzed the genomes of the two fig species, Ficus microcarpa and Ficus hispida, along with that of Eupristina verticillata, a wasp that pollinates Ficus microcarpa.

When we sequenced the trees genomes, we found more segmental duplications in the genome of the banyan tree than in Ficus hispida, the fig without the aerial roots, Professor Ming said.

Those duplicated regions account for about 27% of the genome.

The duplications increased the number of genes involved in the synthesis and transport of auxins, a class of hormones that promote plant growth.

The duplicated regions also contained genes involved in plant immunity, nutrition and the production of volatile organic compounds that signal pollinators.

The levels of auxin in the aerial roots are five times higher than in the leaves of trees with or without aerial roots, Professor Ming said.

The elevated auxin levels appear to have triggered aerial root production. The duplicated regions also include genes that code for a light receptor that accelerates auxin production.

When the researchers studied the genome of the Eupristina verticillata wasp and compared it with those of other related wasps, they observed that the wasps were retaining and preserving genes for odorant receptors that detect the same smelly compounds the fig trees produce.

These genomic signatures are a signal of coevolution between the fig trees and the wasps.

The authors also discovered a Y chromosome-specific gene that is expressed only in male plants of Ficus hispida and three other fig species that produce separate male and female plants, a condition known as dioecy.

This gene had been duplicated twice in the dioecious genomes, giving the plants three copies of the gene, Professor Ming said.

But Ficus species that have male and female flowers together on one plant have only one copy of this gene.

This strongly suggests that this gene is a dominant factor affecting sex determination.

The results were published in the journal Cell.

_____

Xingtan Zhang et al. Genomes of the Banyan Tree and Pollinator Wasp Provide Insights into Fig-Wasp Coevolution. Cell, published online October 8, 2020; doi: 10.1016/j.cell.2020.09.043

Original post:
Researchers Sequence Genomes of Two Fig Species and Pollinator Wasp | Genetics - Sci-News.com

Norman Swan: One of the mysteries surrounding COVID-19, the disease that is caused by SARS-CoV-2, is why some people experience severe life-threatening disease and others don't. Age, male gender and having other problems like diabetes, heart and lung disease and probably obesity, are risk factors. But what about individual differences in people's immune systems? Well, two recent studies have found that to be the case in a significant percentage of people with serious COVID-19 disease. One study looked for genetic patterns and found an effect on immune messages called interferons. There are about 18 interferons in the body and they act like volume controls and orchestra conductors in the immune system once it has been alerted to an attack by a virus. The second study found antibodies against interferon in some people. This has huge implications for a better understanding of the immune system, not to mention more targeted therapies for people with COVID-19. Professor Paul Hertzog is one of Australia's leading experts on interferons. Paul is head of the Centre for Innate Immunity and Infectious Disease at the Hudson Institute in Melbourne.

Paul Hertzog: This study, initiated by Jean-Laurent Casanova who is based at the Rockefeller, and Helen Su at NIH, they've set up actually a global network looking for patients who might have genetic predispositions to getting extremely ill with the Covid SARS-CoV-2 virus. And it is really the first output of that global network of people who are doing the searches.

So firstly it's really the first substantial report that there is a genetic susceptibility of this disease. It's something that we always suspected but this really proves it. And more particularly what is unusual and fascinating is that most of the culprits they found were actually lying in different components of the interferon signalling system.

Norman Swan: They found a relatively consistent genetic problem in people when they looked at their genes, and these genes seem to code for the interferons in some shape or form.

Paul Hertzog: Yes, they identified 12 genes that we knew were involved in susceptibility to infections, particularly respiratory infections, and they happen to be in the interferon pathway, but involved in the production of it, or the response to it. And so they really looked where the light was and they said, well, can we find deficiency in any of these 12 genes? They actually found deficiencies in quite a high proportion of patients, about 3% of them. So I'm sure there are many more to cover because this was really just a very targeted look.

Norman Swan: So 3% doesn't sound too high.

Paul Hertzog: With a million people dying, I think it's a lot of human beings. And I think it is just the tip of the iceberg.

Norman Swan: People have been talking about interferons now for a while, and in fact interferons have been trialled as a treatment for people with COVID-19 disease even prior to these studies coming out. What's the net effect of these genetic abnormalities or these genetic differences?

Paul Hertzog: I suppose what they might enable us to do, Norman, is to use what you would call a precision medicine approach where we can identify people who would benefit and who would not benefit from this. So, for example, if a person has a defect which means they are unable to respond to interferon, and some of these genes are involved in that, it's absolutely pointless giving them interferon therapeutically because they just would not be able to respond. On the flipside, if we identify patients who can't make it and some of the genes are involved in the making of the interferon, then they are more likely to benefit from therapeutic administration of interferon.

Norman Swan: So where does this research go next? Presumably it's a simple test or what?

Paul Hertzog: I think that's a simple test. As I said, I think it might enable us to identify groups of patients who are likely to respond to interferon than those who don't. And if we can talk for a minute about the other paper which involves the identification of autoantibodies to interferon, that's probably in fact a far more fascinating study because autoantibodies, some of your listeners might recognise, are usually associated with autoimmune diseases like lupus where something goes wrong with the immune system, instead of recognising a foreign antigen it turns on itself, and these rogue antibodies can cause disease. So what they found in their second study was that 10% of the patients they looked at, which is a staggering number really, produced antibodies to these type I interferons and would negate its effect. That population of patients won't be able to respond. That has a number of implications. Secondly,

Norman Swan: Before you get to the implications, is the assumption that the autoantibodies pre-existed the infection or were created by the virus?

Paul Hertzog: Their study was nearly 1,000 patients, so there were probably about 100 of them and that they found these autoantibodies. I think in about 10 or 12 of them that they had the opportunity in the samples there to look before they had obvious signs of disease, and some of them did have pre-existing antibodies, but that's just a small proportion of those patients, I think it needs a much bigger study but it tells us that some of them certainly can predate. And that's interesting for a number of reasons because it identifies an underlying condition that we never would have thought of. And the other thing is those patients have no previous signs of other respiratory or susceptibility to viral infections, which raises the question whether this is fairly specific to COVID-19.

Norman Swan: And it also raises a question which a lot of people, at least to my Coronacast podcast ask, if I've got rheumatoid arthritis or Multiple Sclerosis or scleroderma or SLE, one of the other autoimmune diseases, doesn't make me more susceptible to COVID-19? Do any of the other autoantibodies that are around in the community affect interferons in this way?

Paul Hertzog: A really interesting question that has complicated answers, and the answers are yes and no. There are some autoimmune conditions where similar autoantibodies to interferons have been seen. But there are others like lupus where the opposite seems to happen. In lupus it seems a large part of the disease is driven by interferon, and in fact there was a large trial headed by an Australian clinician from Monash, Eric Morand last year that identified blocking antibodies to interferon that actually look like they will have beneficial effects in lupus, so that's quite the opposite effect.

Norman Swan: So this discovery of autoantibodies which might actually be quite significant in a reasonable percentage of people, is there a therapy there?

Paul Hertzog: Good question. Not obviously. It's probably may lieagain, if you're thinking interferon therapy it clearly wouldn't work and less there is some specificity in the antibodies that you could get around. I think there are ways of screening it out. For example, you wouldn't want the samples of those serum in your convalescent serum preparation, so I think there are practical outcomes like that.

Norman Swan: Oh yes, that's right, so if you're taking serum from these people to give to other people and you give them autoantibodies you can make them worse.

Paul Hertzog: Right, so it's another screening test for that. There are B cell and antibody depletion therapies that are used in other autoimmune diseases, and that might be in the area that could be looked at in these patients.

Norman Swan: So what's next for your research, given all this?

Paul Hertzog: Well, it provides us with an opportunity. For us it's yet another example of the importance of the interferon system. We are currently collaborating with Jean-Laurent Casanova in a number of these mutations prior to Covid and we will continue that. What we'll do is drill down to try and find out the mechanism whereby some of these mutations in the interferon system are working, and in fact whether some of them that haven't yet been identified as loss of function and disease contributing might in fact be so.

Norman Swan: Paul, thanks for joining us.

Paul Hertzog: My pleasure, thanks a lot.

Norman Swan: Professor Paul Hertzog is head of the Centre for Immunity and Infectious Disease at the Hudson Institute in Melbourne.

View original post here:
Could genetics explain the mystery of severe coronavirus? - ABC News

How can you make this type of research information into news you can use? Thats a real challenge.

About a year ago, I thought I saw a path to greater use of genetic information by consumers. An ambitious company named Veritas Genetics was offering full genome sequencing to U.S. customers for $599 US. They told me they were planning to expand to Canada. Veritas is backed by considerable brainpower, including its co-founder, Harvard professor George Church, often called the father of synthetic biology.

A full human genome sequence is about three billion base pairs, containing your complete genetic blueprint. By contrast, companies like Ancestry and 23andme only look at certain parts of the genome that provide information about ancestral roots and common medical conditions.

What Veritas seemed to lack is financial backing. This was complicated by the fact that many of its investors were from China, which raised red flags because of possible U.S. regulations. Privacy experts have also told us to be very careful about where our genetic data goes once it leaves our mouth as a bit of spittle. Veritas has suspended their U.S. whole genome testing, laid off some staff, and is currently focusing on COVID-19 tests.

Competitors are cropping up, and theres no doubt you will eventually be able to download your complete gene sequence and scan it for interesting findings. There are already tools out there like OpenSNP that can work with the information you can download from 23andme, deCODEme or FamilyTreeDNA. It can answer questions like am I a fast metabolizer of caffeine?

Read more from the original source:
Keenan: Thinking well beyond COVID-19 - Calgary Herald

This article is co-authored by a patient with metastatic hormone-sensitive prostate cancer who is receiving abiraterone and androgen deprivation therapy treatment in Manchester, UK. The patient relates his personal experiences struggling with the diagnosis, his experience with treatment and the physical, emotional and psychosexual impact on his life. After his diagnosis, the patient has become an outspoken advocate and fundraiser for prostate cancer awareness and wants to ensure that novel treatments with proven efficacy and tolerability, such as abiraterone, are available for all men in his condition. The specialist nursing and physician perspectives, provided by healthcare professionals based in London who are not directly involved in this patient's care, were written in response to the challenges and concerns highlighted by this patient. The role of the specialist nurse as a key healthcare professional in the cancer patient journey, particularly in managing the complex physical and emotional side effects of treatment, is highlighted in this perspective piece. The physician reviews the current difficulties of establishing an effective screening programme in prostate cancer, the common side effects of hormone treatment and the significant progress and challenges in novel drug development and prescription in metastatic hormone-sensitive prostate cancer. While written primarily from the perspective of a patient and healthcare professionals in England, many messages in this commentary would resonate with patients and professionals involved in the care of prostate cancer worldwide.

Oncology and therapy. 2020 Oct 09 [Epub ahead of print]

Tony Collier, Shievon Smith, Michelle Greenwood, Kenrick Ng

Prostate Cancer UK, 53 Tooley Street, London, SE1 2QN, UK., St Bartholomew's Hospital, Barts Health NHS Trust, London, EC1A 7BE, UK., St Bartholomew's Hospital, Barts Health NHS Trust, London, EC1A 7BE, UK. .

PubMed http://www.ncbi.nlm.nih.gov/pubmed/33037517

Continued here:
Living with Advanced Hormone-Sensitive Prostate Cancer and Treatment with Abiraterone and Androgen Deprivation Therapy: The Patient, Nursing and...

Though COVID-19 has stopped many things this year, it hasnt stopped other life-threatening illnesses during Breast Cancer Awareness Month.

Some may be putting off an annual wellness visit or other medical procedures because they dont want to be in a medical center during the pandemic, but American Cancer Society Senior Community Development Manager Kim Durst says breast cancer and other diseases shouldnt be ignored, So if you are concerned because maybe you found a lump or its that time for you to go in and get your testing done, reach out to your healthcare provider. They are taking the precautions at the doctors offices, hospitals, and clinics where you wear your mask, use your hand sanitizer, and they are finding ways now to get people in for their checkups.

The Centers for Disease Control and Prevention states that additional ways to lower your risk of breast cancer include keeping a healthy weight and exercising regularly, limiting alcohol consumption, and asking your physician about the risk of taking hormone replacement therapy or birth control pills.

Read more from the original source:
Schedule Your Breast Cancer Screening this Month - raccoonvalleyradio.com

Olaparib (Lynparza) significantly improved overall survival (OS) versus enzalutamide (Xtandi) or abiraterone acetate (Zytiga) in patients with metastatic castration-resistant prostate cancer (mCRPC) who harbor BRCA1, BRCA2, and/or ATM aberrations, according to results from the final OS analysis of the pivotal phase 3 PROfound trial (NCT02987543).1

In the trial, patients with mCRPC who progressed on previous treatment with a new hormonal agent and harbored BRCA1, BRCA2, or ATM aberrations (n = 245; cohort A) or other alterations in the homologous recombination repair (HRR) pathway (n = 142; cohort B) were randomized 2:1 to receive either olaparib or enzalutamide or abiraterone acetate.

Final OS data from cohorts A and B were presented during the 2020 ESMO Virtual Scientific Program. Results showed that the median OS in cohort A was significantly longer with olaparib than with physicians choice (HR 0.69; 95% CI 0.50-0.97; P = .0175).1In cohort B, the median OS was 14.1 months with olaparib versus 11.5 months with the control (HR, 0.96; 95% CI, 0.63-1.49).

What is exciting about this particular trial is that it showed the feasibility of personalizing care and using precision medicine strategies to preselect patients to maximize the chance of benefit for those who are candidates for these treatments, said Maha H.A. Hussain, MD, FACP, FASCO.We can also help patients avoid unnecessary exposure to ineffective treatments.

Previously published data showed that olaparib resulted in a 66% reduction in the risk of disease progression or death compared with abiraterone or enzalutamide (HR, 0.34; 95% CI, 0.25-0.47;P<.0001).2 Based on these results, the FDA approved olaparib in May 2020 for the treatment of adult patients with deleterious or suspected deleterious germline or somatic HRR genemutated mCRPC who have progressed following prior treatment with enzalutamide or abiraterone.

In an interview with OncLive, Hussain, the Genevieve E. Teuton Professor of Medicine in the Department of Medicine of the Division of Hematology Oncology and the deputy director at the Robert H. Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, further discussed the updated findings from the PROfound trial, its clinical significance in the treatment of patients with mCRPC paradigm, and the promise of precision medicine.

Hussain: PROfound is a randomized phase 3 clinical trial. It is one of the first precision medicine clinical trials to complete; patients were preselected based on specific genomic alterations and then randomized accordingly. Patients with mutations in the HRR genes or DNA damage repair genes were assigned to 2 different cohorts. The primary cohort was [comprised of] patients who had BRCA1/2 or ATM mutations, while cohort 2 included [those who harbored] other genes that are involved in the HRR pathway. Patients were randomized 2:1 to olaparib or standard of care per physicians choice of either abiraterone and prednisone or enzalutamide. The primary end point [of the trial] was radiographic progression-free survival (rPFS), which is a meaningful clinical end point, while OS was one of the several key secondary end points [examined].

Data from the Stand Up to Cancer highlighted the fact that over 20% of patients with mCRPC have significant mutations in the DNA repair pathway or the HRR genes. That [research] underscored the fact that this is a clinically relevant pathway to go after. At the time that [the PROfound trial was being designed] we saw evidence of benefit [with this approach] in other tumors [such as] breast and ovarian cancers, and then subsequently, in pancreatic cancer.

The specific pathway relevance is that both normal cells and cancer cells need to repair themselves when there is damage; the HRR pathway is involved in that repair process. However, are alterations or mutations [are present], the cells are not able to repair themselves and they fall back into a different pathway, which is the PARP pathway. Basically, PARP agents tend to inhibit that enzyme so that the [cancer] cells cannot repair themselves.

[Earlier data from the trial were previously published] this past summer. Johann de Bono, MB, ChB, PhD, of The Institute of Cancer Research was the first author on the publication in the New England Journal of Medicine, which highlighted [data regarding] the primary end point of rPFS. In this particular presentation delivered at the 2020 ESMO Virtual Congress, [investigators] reported OS [data from] cohorts A and B.

We saw that the benefit [with olaparib is] not only in terms of rPFS; the benefit translated into a median OS benefit of over 4 months between the arms, despite crossover from the control arm to the olaparib arm at time of progression. Additionally, the risk of death was reduced by 31%, which is very clinically significant. In [the cohort of patients who harbored the] other 12 genes, other than BRCA1/2 and ATM, we saw a trend in OS improvement but it was not statistically significant. The trend was about a little bit over 2 months of a difference. When adjusting for crossover, the trend improved although it was still not statistically significant. However, several patients in cohort B experienced clinical benefits from treatment. The primary benefit [with olaparib] still seems to be driven by BRCA primarily.

No; the overall safety was very much consistent with what was known about olaparib. The most common adverse effects observed included anemia, nausea, and fatigue. Most of these were low-grade events, aside from the anemia. Many of these patients were heavily pretreated; while they might have previously received abiraterone or enzalutamide, they would have also received chemotherapy and other potential anticancer treatment and be fairly advanced in the course of their disease. The findings, overall, are really not surprising and the safety profile very much consistent with what has been observed with the agent in other tumors.

We have reached a major benchmark in the management of this disease. Ever since the original observations regarding androgen deprivation [therapy] in prostate cancer and subsequent treatments, and certainly since the time I entered the field in the early 1990s, prostate cancer management has been more of a one-size-fits-all approach. In fact, when we give chemotherapy and hormone treatment we don't preselect [patients].

We still have [a lot of work to do]. Patients with metastatic castration-resistant disease continue to die from prostate cancer; they also suffer from pain and other factors involved with this disease. This [research] highlights the feasibility of performing precision medicine trials. It also shows us that meaningful clinical benefits could be achieved in these patients. I would hope that our partners across the spectrum will invest further in conducting more clinical trials.

The observation that we've seen with olaparib also opens up the door for potential combination clinical trials, both in castration-resistant disease and potentially in earlier stages of disease, where we might get a better return on investment from a clinical perspective.

Genomic profile evaluation for patients is critical moving forward, not only for the purpose of treatment for the patient. Conducting or counseling the patient regarding germline testing and tumor genomics evaluation in preparation for future treatment is also very critical. Obviously, genetic testing is associated with genetic counseling, [which may allow patients] and potential blood relatives [to get ahead of the game].

Tissue-based genomic evaluation will open the door for the patient to explore different treatments, and [certain] genomic alterations might qualify them for different clinical trials opportunities. [This work] underscores the hope for patients that their cancer can be managed better with genomically targeted treatments, specifically, in this case, the PARP inhibitor. [Now we can build on] these observations in terms of different treatment strategies and combinations.

Read the original here:
PROfound Trial With Olaparib Shows Feasibility of Personalizing Care in mCRPC - OncLive

NEW YORK, Oct. 12, 2020 /PRNewswire/ --Nutrafol, the award-winning hair wellness supplement backed by top physicians, celebrities and hairstylists alike, announces the positive results from its new clinical trial, an industry-first study presented on hair growth in menopausal women. The 6-month double-blind, randomized, placebo-controlled study assesses the safety and efficacy of Nutrafol's Women's Balance formulation in improving hair growth and quality in perimenopausal, menopausal and postmenopausal subjects with self-perceived thinning hair. This milestone establishes Nutrafol as the only hair supplement brand to present research specifically for menopausal women and continues to solidify Nutrafol as an innovator and trusted leader in hair science.

Forty percent of women experience hair loss by age 40, and that number continues to increase as women age.1 Nutrafol created Women's Balance - which first launched in 2019 - in response to the complex hormonal needs of women who are going through or have gone through menopause. It is the only hair wellness supplement clinically formulated to address the root causes of hair thinning in perimenopausal and menopausal women. Featuring a patented Synergen Complex Plus, it includes clinically effective natural ingredients like saw palmetto, ashwagandha and maca, known to support hormone health before, during and after menopause.

"There is unfortunately a lack of research for the physical and emotional effects that menopause has on women," said Dr. Sophia Kogan, Nutrafol's co-founder and Chief Medical Advisor. "At Nutrafol, our mission is to empower women to take control of their hair health, and hormones. After years of research, rigorous clinical testing and the accumulation of unsurpassed data, we have a proven and effective option with our Women's Balance formulation."

To assess the safety and efficacy of Women's Balance for perimenopausal, menopausal and postmenopausal women, Nutrafol conducted a 6-month randomized, double-blind, placebo-controlled trial. Results were significant for objective measures of hair growth, including terminal, vellus and total hair counts. There was a progressive increase in hair counts for Nutrafol subjects compared to placebo at three and six months. Additionally, daily administration of Nutrafol resulted in significantly less shedding compared to placebo. This was accompanied by significant visible clinical improvement in hair growth and quality in the active group, as assessed by a blinded physician investigator. Conclusively, the study verified that the daily intake of a novel supplement with bio-optimized phytoactive ingredients to specifically address multiple underlying factors that compromise hair growth was safe and effective in improving hair growth and quality in women going through menopausal transition. The Primary Investigator of the study was Dr. Glynis Ablon, MD, FAAD and founder of the Ablon Skin Institute & Research Center, an independent clinical research site specializing in dermatology clinical trials.

"Menopause is a disruptive time for women between the hormonal shifts and changes in their bodies that are out of their control," said Dr. Glynis Ablon MD, Primary Investigator on the clinical study. "Nutrafol has pioneered a new way of thinking about the science of hair wellness as it relates to menopause. With safety and efficacy at the forefront of everything the brand does, the published data supports the clinical effectiveness of the Women's Balance formulation for menopausal women. This provides physicians with a solution for their patients, and gives menopausal women the opportunity to take control of their menopausal transition and beyond."

To learn more about Nutrafol and Women's Balance, please visit http://www.Nutrafol.com or speak with your Healthcare Provider.

About NutrafolNutrafol pioneered the hair wellness category with its integrative approach to hair health, using a first-of-its-kind patented formulation of clinically effective, natural, medical-grade ingredients to support whole body wellness from within. In multiple clinical studies, Nutrafol has been shown to improve hair growth in both men and women by multi-targeting root causes of thinning hair, including stress, hormones, environment and nutrition. Nutrafol's team of doctors and researchers continue to seek out scientific advancements at the forefront of genetics, anti-aging medicine, phytoactive and biotechnology to remain on the cutting-edge of hair health innovation. Nutrafol has been adopted by over 2,700 Healthcare Providers across the U.S. for its trusted, reliable results and has received numerous prestigious accolades.

1American Academy of Dermatology

PR ContactBehrman Communications / Gianna Cesa[emailprotected] 212.986.7000

SOURCE Nutrafol

http://www.nutrafol.com

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Nutrafol Pioneers Hair Wellness Industry with New Study that Reveals it Safely and Effectively Improves Hair Growth in Menopausal Women - PRNewswire

Jennifer Wong, RPA-C

ASTORIA, N.Y. (PRWEB) October 14, 2020

Blame it on the hormones? Well, maybe. In some cases, notes Jennifer Wong, a certified registered physicians assistant specializing in dermatology with Advanced Dermatology PC, the dark skin patches called melasma occur at the same time a woman experiences hormonal changes. But were still learning about the nature of the connection.

In this country, as many as six million people a year ninety percent of them women experience darkened patches of facial skin, usually brown or gray, the result of overproduction of the skin pigment melanin.

In particular, says Wong, women with darker skin tones are more susceptible because their skin has more active melanocytes the skin cells that produce melanin. Genetics also seems to play a role: having a family member with melasma increases the possibility of developing it yourself.

And, of course, there is the role of the sun. The sun triggers our melanocytes, observes Wong. With melasma, very little exposure may cause the discoloration. Unlike age spots, melasma is not due to cumulative sun, and actually often occurs in young women. In some cases, even the light of our computer or cell screens can contribute to melasma.

Melasma usually appears on the center forehead, over the brows, on the bridge of the nose, on the chin, and on the upper lip. All places that get sun exposure, observes Wong. In some cases, melasma occurs on other frequently exposed areas like our forearms.

When melasma co-occurs alongside hormonal changes due to pregnancy, birth control pills, or hormone replacement, it can spontaneously resolve when hormones return to previous levels, for example after the pregnancy or if medications are discontinued. But in other cases, notes Wong, melasma persists. While it is medically harmless, its appearance on ones face can be distressing. Fortunately, we have a number of options to lighten melasma.

With that in mind, Wong makes the following suggestions:

5 Tips on Treating Melasma:

1. First, get a clear diagnosis: Its important, says Wong, to rule out any skin condition that requires medical treatment. A skin specialist can do an examination and, if needed, a biopsy. Once you have a clear diagnosis, you can work with your provider on a treatment plan.

2. Skin lighteners can help: In particular, notes Wong, topical use of hydroquinone or HQ can be effective. HQ comes in varying strengths, including less concentrated over-the-counter formulations, as well as combined with other topicals, such as the retinoid tretinoin and a corticosteroid, in a so-called triple cream. Other topical lighteners include azelaic acid and kojic acid. Your skin-care specialist can help guide your choices.

3. Choose OTC products with care: An alarming number of OTC skin lighteners contain mercury, advises Wong, a neurological toxin that can also injure the children and partners that people come into close contact with. Your skin specialists guidance can be especially helpful because some products do not clearly identify ingredients, using different terms for mercury, including calomel, cinnabaris, hydrargyri oxydum rubrum, or quicksilver. In addition to hidden mercury, weve also seen products with unlisted steroids, which can cause skin damage.

4. Outpatient procedures can help, too: Lasers, explains Wong, can penetrate down to melanocytes to block melanin production, while chemical peels can remove hyperpigmented surface skin. Again, your skin specialist can explain outcomes, time involved, and side effects to help customize a treatment plan that is the best fit.

5. Throw shade on the chance of reoccurrence: The sun activates our skins production of melanin, notes Wong. Melasma can be triggered by minimal exposure, regardless of season or weather, so patients will want to be vigilant about protecting themselves from the sun every day, all year. A broad-spectrum SPF 30 mineral sunscreen with zinc oxide or titanium dioxide can help physically block rays. Patients will also benefit from protective clothing, including a wide-brimmed hat and sunglasses.

Fortunately, Wong concludes, patients can take action now to reduce the appearance of melasma, as research continues to connect the dots between hormones and other factors.

Bio: Jennifer M. Wong, RPA-C Physician Assistant. Ms. Wong has comprehensive experience in medical and cosmetic dermatology for all ages.

Advanced Dermatology P.C. and the Center for Laser and Cosmetic Surgery (New York & New Jersey) is one of the leading dermatology centers in the nation, offering highly experienced physicians in the fields of cosmetic and laser dermatology as well as plastic surgery and state-of-the-art medical technologies. http://www.advanceddermatologypc.com

View original post here:
Jennifer Wong, RPA-C with Advanced Dermatology PC, Offers Tips on Reducing the Hyperpigmentation of Melasma - PR Web

Katherine Crew, MD, is a physician-scientist whose work in breast cancer risk, prevention, and screening has helped move the needle in breast cancer research. Dr. Crew is a member of the Cancer Population Science research program at the Herbert Irving Comprehensive Cancer Center, associate professor of medicine and of epidemiology at Columbia University Irving Medical Center, and a medical oncologist at NewYork-Presbyterian Hospital.

Weve made a lot of strides in the past few decades and part of that is because we are detecting breast cancer a lot earlier with improved screening and due to our improvements in treating breast cancer, says Dr. Crew. There are always more improvements to make along the way but overall survival for breast cancer, since the 1980s, has improved by about 40%, and its due to all of those efforts, including increased advocacy and increased awareness of this disease.

Where are we now in treating breast cancer?Through epidemiological studies, we have a better understanding of the main risk factors for breast cancer, whether it be age and reproductive factors that influence exposure to the hormone, estrogen, and were learning a lot more about genetic risk for breast cancer.

Back in the mid-1990s it was all about BRCA1 and BRCA2 mutations but now, in the past several years, were testing for multiple genes that can predispose to breast cancer as well as other cancers. And with next generation sequencing, were able to sequence the whole genome much more cheaply and much more quickly. This has led to an increase in our understanding about genetic susceptibility to breast cancer in particular.

Once a person knows about her genetic risk factors or that they are predisposed to breast cancer, what then?We know if a woman has a genetic predisposition, she has the option for enhanced screening, with not just mammography, but more sensitive screening tests like breast MRI. If she has a high penetrance gene she may opt for prophylactic mastectomy. Certainly when Angelina Jolie wrote her Op-Ed in The New York Times about getting a bilateral mastectomy after she found out she had a BRCA1 mutation that really helped to increase awareness.

Now that were finding these more moderate risk genes it has becoming harder to know where to draw the line. We dont want women to do unnecessary surgery or to do unnecessary procedures because that may be potentially harmful. I think were still learning what to do with that information. Knowing more about a persons genetic risk has definitely helped to make breast cancer risk much more personalized and we are always trying to provide the right intervention for the right level of risk, per individual.

There are many types of breast cancer. Can you give us the lay of the land of the main subtypes?The different subtypes of breast cancer all behave differently and we treat them differently. The most common is the estrogen receptor positive breast cancer, which counts for about 70% of all breast cancers and we know that these types of breast cancers respond very well to anti-estrogen therapy. More recently weve been using a class of drugs called aromatase inhibitors in post-menopausal women. In many ways thats been one of the most effective targeted treatments that weve had for breast cancer we can see up to a 50% to 65% relative risk reduction in breast cancer relapse with these drugs.

There is HER2-positive breast cancer and recently, theres been an explosion of new drugs for treating this subtype. Within just the past few years, at least four or five additional drugs have been approved for HER2-positive breast cancer. Although it is a more aggressive form of breast cancer, it is also a type of breast cancer that responds well and is very sensitive in general to chemotherapy and targeted therapy. Even in patients who have metastatic disease, women are living longersometimes for more than five yearswith advanced breast cancer.

The most challenging type of breast cancer to treat is triple negative breast cancer, meaning that it is negative for the two hormone receptors estrogen and progesteroneand also negative for the HER2 receptor. We cant treat it with anti-estrogen therapy and we cant treat it with any HER2 targeted therapies. In this case the main treatment option is chemotherapy, which has its own set of side effects associated with it.

Is this a focused area of research right now?Yes, its an area very ripe for new discovery and research. Recently there was drug approval for immunotherapy for triple negative breast cancer, particularly in combination with chemotherapy. Immunotherapy is a very new type of therapy thats gotten a lot of attention in the press and in the oncology world.

Tell us how immunotherapy could impact breast cancer.Currently, immunotherapy is approved in patients with metastatic triple negative breast cancer but there are a lot of clinical trials that are looking to expand the use of this medication for other breast cancer subtypes. Typically in cancer in general we test these new drugs in patients with advanced cancer who have fewer treatment options and in those cases we may only prolong their survival by a few months. Its much more exciting when we can then take these drugs, if theyre found to be safe in patients with early stage disease, to see if we can improve cure rates. There are ongoing trials testing immunotherapy in patients with early-stage breast cancer, especially if they have high risk disease, to see if we can prevent a relapse and therefore cure them.

What are the other exciting areas of breast cancer research right now?A big trend within oncology and within breast cancer in particular is the de-escalation of therapy. Can we spare some patients from unnecessary treatment? We dont want to over treat breast cancer. We want to treat the high-risk patients but the ones with a more favorable breast cancer, we want to spare them some of the side effects of chemotherapy, for example.

One major breakthrough is as we understand the biology of these tumors a little bit better, we can better classify patients. There are different molecular tumor tests we can use now, including Oncotype Dx, MammaPrint, breast cancer index all of these new tumor tests gives us the opportunity to personalize a womans breast cancer care. Based upon a womans tumor biology, we can assess who needs chemotherapy, who may benefit from extended hormonal therapy, who can do well with just five years of anti-estrogen therapy, and then we can spare them from a lot of the side effects that weve seen from some of these drugs. I think that de-escalation of care has helped cut costs and certainly reduces long-term side effects in our breast cancer patients. We dont want to keep adding on expensive treatments on patients who dont necessarily need it.

You run the High-Risk Prevention Clinic. Whats new in prevention?Similar to the breast cancer treatment field, in the preventive setting you have to look at this not as a one-size-fits-all for women. We can now better refine what a womans risk is and give individualized guidelines for them. Prevention is getting more complex. We dont just test for BRCA1 and BRCA2 genes; there are multi-gene panels that we can test for. Now theres a lot of interest in polygenic risk scores (PGS), so rather than looking at one gene we can look at a bunch of genetic variants sometimes hundreds of genetic variations and come up with a risk score based upon those hundreds of variants. Based upon that score, we place women on a spectrum of risk and then use that to make recommendations about screening, lifestyle modifications, preventive surgeries, and even medications. For example, anti-estrogen drugs have also been shown to be effective in the prevention setting.

How has screening for breast cancer evolved or changed?There are major advances on the screening front as well. For a long time we mainly only had 2D digital mammography and now we have 3D mammography, or tomosynthesis. Rather than just having two views of the breast you can have serial slices of the breast and that can help to increase the sensitivity of the mammogram, particularly in women who have dense breast tissue because having dense tissue can lower the sensitivity of the mammogram for early detection.

There is actually a lot of controversy around screening. Just as we know there are more than one type of breast cancer and more than one level of risk, were trying to adopt less of this sort of one-size-fits-all for breast cancer screening. For instance, not all women need to get yearly mammograms, maybe just higher risk women with dense breast tissue could get enhanced screening with either ultrasound or MRI. But for the majority of women who are not high risk, perhaps we can think about cutting back on mammography screenings. Current guidelines are that if you are average risk you can wait until youre 50 to get mammograms every two years, rather than yearly. Maybe less frequent screenings can also reduce some of the harms of screenings, like increased biopsies.

What does the future hold for breast cancer research and treatment?All of the new drugs and targeted therapies have definitely incrementally advanced the field.

The most exciting is this idea of precision medicine, both for prevention and for treatment, and using genetic information to assess breast cancer risk, having the genetic information of the tumor tissue to assess the aggressiveness of the cancer and being able to tailor treatments specific for individual patients is what we are working towards. I think that more than anything else having that genetic information tailoring our carehas really put more tools in our tool box in terms of what we can offer patients.

-Interview by Melanie A. Farmer

Related:Five Questions with Dr. Eileen Connolly: 'Less is More' Adage Signifies Shift in Breast Cancer Radiotherapy

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Q+A: Katherine Crew, MD, on the Many Advances in Breast Cancer and What's to Come - Columbia University Irving Medical Center

This article is the part of a monthly series of stories focused on cancer issues. Denver7 is proud to partner with the American Cancer Society, Cancer Support Community, Colorado Cancer Coalition and Sarah Cannon Cancer Institute at HealthONE to bring you these stories, tips and resources.

DENVER -- This year, the American Cancer Society estimates that 4,530 women in Colorado will be diagnosed with breast cancer in 2020 and 640 women will die from the disease.

Breast cancer screening is important and can detect the disease when symptoms appear, or before there are any signs. The following American Cancer Society guidelines are for women at average risk:

For more information on screening and risk factors, visit https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html

If a patient had to reschedule their screening in the midst of the pandemic or are due for their screening, they should talk to their healthcare team. Providers can discuss balancing the risks and benefits of being screened now or postponing for a later date, considering personal and family history, other risk factors, and the timing of the last screening test.

Signs and SymptomsIts important to know how breasts normally feel and to be aware of any changes. A common symptom is a new lump or mass, but other things to be aware of include:

If you notice any changes, contact your doctor. For details visit https://www.cancer.org/cancer/breast-cancer/about/breast-cancer-signs-and-symptoms.html

Mammogram Q&AI'm pregnant or breast-feeding and due for a test. Should I wait?

I have a breast implant. Can I still get a mammogram?

What else should I know?

Continued here:
What you need to know about breast cancer and screenings - The Denver Channel

Ginger is a plant that has been used to treat ailments for thousands of years. Not only is ginger a delicious addition to cooking because of its spicy and unique flavor, but it's also great for your health.

Here are six health benefits of ginger and how to add it to your diet.

A small 2017 study tested the antioxidant effects of ginger in cancer patients receiving chemotherapy. Those who received a daily ginger extract had higher levels of antioxidants and lower levels of oxidative stress than the placebo group.

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Typically, inflammation goes away once your body repairs itself. But, when you're experiencing oxidative stress, it can cause chronic inflammation. This causes your body to damage healthy cells, tissues, and organs. Chronic inflammation may lead to diseases like heart attacks or chronic pain like arthritis.

Ginger contains a compound called gingerol. Gingerol is known for improving gastric motility the passage of food through the body and suppressing muscle spasms. This can help settle the stomach and reduce symptoms of nausea and vomiting.

Ginger is also a safe and effective herbal remedy for pregnant women with morning sickness. A small 2009 study tested the effectiveness of ginger capsules on pregnant women experiencing nausea and vomiting. Pregnant women who took four 250mg ginger capsules daily for four days experienced less nausea and less vomiting than women who received a placebo.

In a 2015 study, scientists reviewed previous research looking at the effects of ginger on menstrual pains and concluded that 750 to 2000mg of ginger powder can help relieve pain during the first three to four days of the menstrual cycle.

There is also some evidence to suggest ginger can help control blood sugar levels in people with diabetes by increasing glucose uptake in muscle cells without insulin.

Ginger stimulates digestive enzymes responsible for moving food through the body more quickly, which prevents gas. "[It] helps the body break down gas and get rid of gas more effectively," Ankewe says.

According to Anekwe, you can easily incorporate ginger into your diet by:

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6 science-backed health benefits of ginger and how to add it to your diet - Business Insider India

Youre powering through your day like a boss. A Zoom meeting here, a report thereyup, youre feeling unstoppable. Nothing can bring you down. That is, until its 4 p.m., and all of a sudden, you want to take a nap. You wonder where your energy has disappeared to as you slog through email after email, wishing that quitting time wasnt a whole hour away.

If youve experienced this phenomenon, youre far from alone.Several studies have confirmed the so-called afternoon slump, including one from The National Sleep Foundation that pointed a sharp drop in circadian rhythm that plummets between 2 and 5 p.m. every day.

Tiredness is a fact of life, no matter what time of day it is. Max Kerr DDS, D-ABDSM, a dental sleep expert with Sleep Better Austin, emphasizes that its extremely common for people to feel tired, even if it goes beyond the afternoon slump.

First, give yourself a break, he says. Life is tough. We have a million commitments and not enough time. Relax and take care of yourself. You have to make your health a priority, because no one else will.

Dr. Kerr adds that although its normal to feel tired, you dont have to keep pushing through that afternoon fatigue when there are options available to you. He advises, Seek out a sleep coach, ask your primary care physician for a Home Sleep Test, get your blood tested, and give yourself the gift of purposeful movement. Conquering fatigue can open up life and joy in a most profound way as well as positively impact everyone around you.

It can also help to know why you face afternoon tiredness each and every day. Here, three medical experts address the question: Why am I always so tired in the afternoon? Here are 13 possible reasons why.

Dr. Ilene Ruhoy, MD & PhD, and Gut Council Member for the probiotics company Jetson, believes that our energy states greatly depend upon our hormone levels, such as glucocorticoids, leptin, melatonin, and more, she says. These hormones can be impacted by our sleep and eating habits.

Dr. Ruhoy explains, In the mid-afternoon, levels of these hormones are low. However, the absolute levels and the control of secretory rhythms can be influenced by meal and sleep patterns. Sleep fragmentation, poor sleep hygiene, and sleep deprivation all contribute to the feeling of fatigue in the mid-afternoon when hormones are low.

If you suffer from depression, you know how hard it can be to get out of bed some mornings. Pushing yourself through the day can naturally make you feel depression-related fatigue in the afternoon. The insomnia you experience from depression can also cause you to lag mid-day.

Dr. Abe Malkin, M.D. M.B.A. of Concierge MD LA says, Studies have shown that 75% of people suffering from depression show symptoms of insomnia while the other 25% suffer from hypersomnia, which is excessive daytime sleepiness.

Many of us simply forget to drink water throughout the day if we dont make it a priority. All those meetings and phone calls can push hydration way down on your to-do list, but if you want to beat that afternoon slump, drinking up is key.

Water is the main component of our bodys structure, Dr. Kerr notes. When we are habitually dehydrated, it can affect the normal functioning of our body. The harder our body has to work for its normal functioning, the more energy is needed. The less efficient we are, the more tired and fatigued we become.

In other words, regularly sipping that H2O might even make you more productive.

Related: Can You Drink Too Much Water?

Dr. Ruhoy details, Excessive food consumption, sugar and processed food intake, and poor eating habits, such as eating too many meals, doing stressful eating, or doing hurried eating, contribute to fatigue. Minimize or eliminate sugar and processed foods. These foods contain substances that promote inflammation and can disrupt the hormonal balances that impair our rhythms.

She says that in simpler terms, the post-sugar crash is a real thing. You may want to rethink that 2 p.m. doughnut if you want to stay energized through the afternoon.

In addition to what youre eating, it also comes down to when youre eating. Lunch in the middle of the day could be contributing to your lethargy, and you may need to tweak your mealtimes.

Leptin levels, the hormone that suppresses hunger, is low at noon and lowest at approximately 4 p.m. of our 24-hour cycle. Meals in the morning and early evening, over time, will help the daytime fatigue. Studies have shown fasting improves energy state and it may be that it is not truly fasting at all but rather a more natural meal pattern, Dr. Ruhoy states.

If youre someone who feels anxious as soon as your alarm goes off, its no wonder that you feel depleted in the afternoon.

Dr. Malkin says, A chronic anxiety sufferer will still feel exhausted even after a full nights rest because of constant fear when there is no real danger. It is best to schedule an appointment with your doctor to help pinpoint the issue and get treatment to help combat the anxiety.

Related: What Is Social Anxiety?

Our body uses sugar for energy, Dr. Kerr says. The carbohydrates that we eat are converted to glycogen and transported throughout our body in our blood. Insulin will move the sugar from our blood to the cells that need it. If our insulin metabolism is off, which can be caused by diabetes, then our blood sugar can be too low or too high. This can impact the sugar available to our nervous system in order for it to function appropriately. When this happens, we will become very fatigued and sometimes very disoriented. Insulin metabolism is negatively impacted by poor diet and poor sleep.

Heres some major motivation to get your sweat on: exercise just might eliminate your afternoon slump altogether. Exercising regularly can help combat fatigue, Dr. Ruhoy says. Exercise promotes mitochondrial efficacy and it does not require triathlons or climbing Mount Everest. Daily movement helps maintain systemic blood flow and natural levels of adrenal and hypothalamic hormones throughout the day.

Book a morning spin class, sneak in a lunchtime run, or do some calming-yet-calorie-burning yoga at the end of the day.

Related: Best Workout Apps 2020

Dr. Ruhoy explains that sunlight is a huge component of setting proper circadian rhythm, the biological process that regulates our sleep-wake cycles. That means that your body is craving a noon walk in the sunshineor even better, get out to walk in the sun as soon as you wake up.

She says, We often focus on sleep, which is important to be sure, but part of that cycle includes wake, which is one reason why regular meal patterns can be crucial. But getting outdoors each day is important to simulate that rhythm. It does not have to be a sunny day as all that is needed is natural light.

If youre a coffee-drinker, youre likely already aware that if you guzzle a few cups in the morning, it could result in an afternoon crash fueled by a lack of java. And according to Dr. Malkin, the pandemic has been marked by an increase in caffeine all around.

The standard morning cup of coffee became morning, afternoon, and evening joe to help us stay up for Netflix binges and try to function during a Zoom call the next day, he says. Im all for a shot of espresso, but in moderation. When taken in excess, [caffeine] will quickly give you the ultimate jolt but remember what goes up must come down.

To pace yourself, he says that a good rule of thumb is to drink a glass of water equal to your cup of coffee or other caffeinated beverage.

When you find yourself with a few free minutes during the day, were guessing that youre scrolling through social media. Although this can provide an entertaining, or even mindless, diversion, it could result in exhaustion later. Too much screen time isnt good for anyone, Dr. Malkin says. Our brains are actively working to absorb all the images, but lets not forget that the brain is the bodys command center. It gives out all the instructions for when its time to eat, sleep, or work. This is our personal computer which also needs time to reboot just like an athletes body after a rigorous workout.

There are some health conditions that can lead to overall fatigue, the afternoon slump included, and one of those disorders is narcolepsy.

Dr. Kerr says, Narcolepsy is a chronic sleep disorder characterized by overwhelming daytime drowsiness and sudden attacks of sleep. People with narcolepsy often find it difficult to stay awake for long periods of time, regardless of the circumstances. Narcolepsy can cause serious disruptions in your daily routine.

If you suspect that you may have narcolepsy, its a good idea to schedule an appointment with your doctor.

Stress is a natural, albeit less-than-desirable, part of everyones lives. And needless to say, for many reasons, stress has become even more rampant during the pandemic. When youre stressed out, it can definitely take its toll on your daily energy level.

Celebrity interviews, recipes and health tips delivered to yourinbox.

Dr. Ruhoy shares, Emotional, physical, and mental stress can wear us down and make us less motivated to accomplish tasks or engage in social activities, and over time, the effects of stress can fatigue our cells. Stress has real physiologic effects that can ultimately cause fatigue.

Next up, find out if weighted blanket really help with insomnia.

Excerpt from:
Why Am I So Tired In The Afternoon? 13 Reasons Why - Parade

The president has had a life-threatening, infectious disease for over a week, and he and his doctors havent been very transparent about the timeline and course of his affliction. In lieu of detailed disclosures, reporters have to piece together his condition based on the treatments hes been receiving.

Trump was started off on an experimental therapeutic an antibody cocktail and then advanced to another remdesivir. The other biomolecules coursing through Donald Trump's system (and this week's headlines) are corticosteroids, called dexamethasone.

You may have heard of cytokine storms, where the body's immune response to severe COVID-19 bombards healthy cells, making the illness worse. Trump has been given dexamethasone, an immuno-supressant that doctors prescribe to temper that effect. Unlike the other experimental treatments, dexamethasone is common and somewhat easy to access. However, it is rarely administered to a patient with a case as (self-)reportedly mild as Donald Trumps. In an interview with New York Magazine's Intelligencer, the co-author of a recent study testing dexamethasone elaborates:

That lack of evidence is concerning as Trump heads into a critical point in the course of his illness. COVID-19 is known for being a bit of a roller coaster, with intermittent fevers, mysterious symptoms, and rapid declines. Abraar Karan, a physician with experience treating patients with COVID-19, told Monique Brouillette at Scientific American that some people have turned corners and left the hospital, only to come back feeling much sicker, with even worse oxygen levels and possibly other harm to the bodys organs.

It is theoretically possible that the early steroid treatment may ward off a dangerous auto-inflammatory reaction. But beyond the inherent risks of immuno-supression, corticosteroids may also cause behavioral side effects in the President. Trump's cognitive and behavioral state has been a point of concern for years. Potent steroids such as dexamethasone are known to increase appetite, decrease restful sleep, and bring about heightened "maniacal" energy states.

As the nation enters the weekend, Speaker of the House Nancy Pelosi is rolling out a 25th amendment commission, Trump is boasting a miraculous recovery with a Fox News doctor, and the rest of us continue to wait and learn how biology will run its course. For better or worse, the side effects our president experiences may prove to have historical consequences. To my knowledge, roid rage has never been a factor in nuclear geopolitics.

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A tiny particle collider yields new evidence for a type of 'quasiparticles' called anyons - Massive Science

Beta blockers are often prescribed for high blood pressure, especially if the patient has suffered a heart attack. A new study shows they may not be as effective as once thought.

The study was done in Italy at the University of Bologna. According to researchers, it appears that these beta blockers may not be as effective in women patients as they are in men. Data indicated that women had a higher rate of heart failure than men when they had angina or a heart attack.

The study had 14,000 participants from 12 different countries in Europe. Each one had a diagnosis of high blood pressure, but none of them had a heart disease diagnosis. According to the research, women may have an almost five percent higher risk for having heart failure after a heart attack when taking beta blockers. For those who didnt take the medications, the rate of heart failure was about the same for both men and women.

Researchers dont know the cause for this possible difference. One theory is in the interaction between the beta blockers and hormone replacement therapy. It is obvious that more research focused on women is needed. According to doctors and scientists, research often leads to blanket statements that may not hold true for both men and women.

Women present differently with heart issues than men. They also have a unique physiology from men, which leads to the idea that they may react differently to the same medications as men. Other researchers say that beta blockers pose a risk for anyone, whether the patient is a man or woman.

Beta blockers do their work by blocking the transmission of the hormone epinephrine, which is better recognized as adrenaline. These medications slow down your heart rate as well as the force with which it beats. The result is that your blood pressure is also lowered.

The medications have a secondary job which is to open up the veins and arteries for better blood flow. Not all beta blockers work the same. Some focus on the heart rate while others also impact the blood flow. Some popular brand names of beta blockers include Sectral, Corgard, Zebeta, Toprol XL, Tenormin and Inderal.

Beta blockers arent usually the first line of defense against high blood pressure. Diuretics are often prescribed first. Beta blockers may be prescribed if other medications arent effective and with other drugs designed to lower blood pressure.

Doctors may prescribe these medications for angina, heart attacks, irregular heart rhythm, and migraines. They are often given with other medications.

Beta blockers arent usually recommended for people with asthma because it may trigger an attack. It is also not the first choice for people with diabetes because it can mask signs of low blood sugar.

Until more research is done, it is important to discuss medications like beta blockers with your physician and to tell them everything about your medical history to ensure it is the right choice for your health condition.

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Senate Bill May Give More Authority to the FDA for Drug Recall - Med News 365

Katie Byard| For the Akron Beacon Journal

Weve got big news about this little root beer stand that has persevered.

For this first time in its 67 years, the B&K Root Beer drive-in in Cuyahoga Falls, a neighborhood staple, will stay open all year. Previously each year since 1953 the stand closed in the fall.

Loyal customers who in years past have stocked up on pints and quarts of coney dog sauce for the winter are rejoicing.

Weve weathered the storm. Alot of these smaller businesses have not made it," through the COVID-19 pandemic, said Scott Reynolds, who, along with his wife, Christy, owns the old school place at 737 Munroe Falls Ave.

The Reynolds purchased the business in 2015, becoming independent operators of the B&K that years ago was part of the long disbanded B&K drive-in chain.

This has been our best year ever, Reynolds said, noting he wants to keep the momentum going. Weve been very fortunate with all our loyal customers and new ones that discovered the places coney (Spanish) dogs, kraut dogs, hamburgers that are made fresh upon ordering, soft-serve ice cream and more.

I can walk here if the weather gets too bad, said customer Larry Dean, 79, who became a regular about four months ago, after moving nearby to the stand, tucked in a neighborhood.

Last week, Dean, a retired warehouse and inventory manager, drove to the B&K to pick up lunch for himself and his wife. He got his regular order: one coney dog ($2.40), one kraut dog ($2.40), a hamburger ($2.80) and fries ($1.65 for a small order; $2.25 for a large).

Americans are craving more comfort foods during the pandemic, food industry officials say, and the B&K offers familiar eats.

Familiar but upgraded Reynolds says.

Since taking over in 2015, Reynolds, 45, and his wife have kept the vintage vibe freshening up the familiar orange and brown paint while making changes.

The stand now serves one-third pound burgers (larger than before the Reynolds took over) that are formed with the hamburger press that Christy Reynolds grandmother used.

Buns are from Lakemore's Ideal Bakery.

They stand up to our burgers, Scott Reynoldssaid.

Hamburgers previously only offered on Tuesdays are now on the daily menu.

Also joining the daily menu is soft-serve ice cream. One flavor is offered each week.

I am happy to report I have added the B&K to my list of fave area burger places. I brought a couple of cheeseburgers home (including one with grilled onions) for my hubby and me to eat. The stands burgers are straightforward and filling. And, yes, I enjoyed the bun that melded nicely with the cheese and meat, but did hold up.

We also enjoyed a kraut dog (a hotdog topped with homemade sauerkraut that has a sweet flavor), a coneydog (topped with homemade coney sauce) and french fries.

Sides including french fries, tater tots, onion rings, mozzarella cheese sticks are now deep fried. Previously, they were cooked using an air method without grease. Reynolds said customers wanted that classic fried taste.

The stands side of sauerkraut balls isfrom Akron-based Ascot Foods, with roots in the formerBunny B Sauerkraut Balls & Ice Co.

It was rough for the first few years after the couple bought the stand in 2015, Reynolds said.

He noted the business finances were stretched with the purchase of new equipment, including new freezers and refrigerators.

We didnt really know what we were doing at first, he said.

Reynolds, a maintenance supervisor at the Ford Motor Co. plant in Brook Park, and his wife, Christy, a nurse, were looking for an investment when Christy spotted an advertisement saying the stand was for sale.

The idea of running a family business appealed to them. Their children Scott, a fireman;Brian; and Madison, a college student, all work at the stand.

Brians availability to work full-time at the stand now is helping to drive the decision to stay open all year.

The stand is one of three independently operated B&Ks in the area.

Initially the stands were part of the B&Kchain, which began in Michigan City, Ind., in the 1940s. B&Kstands for Bergerson & Kenefick.

Sheila Trombka, a part-time cook at the Cuyahoga Falls stand, is a daughter of Al and Cathy Emich, who acquired the stand in 1958 and sold it in 1996 toVic and Dixie Davis, who sold the stand to Scott and Christy Reynolds in 2015.

Trombka has worked at the stand for virtually her whole life. She learned to wash root beer mugs when she was 5 years old and when she was 9, she ran the register. By the time she was 11,she was a carhop. Now her sons, James, 22, and Jonathan, 18, work part-time there.

She showed us the ropes. We love her to death, Scott Reynolds said.

I came with the building, Trombka said.

About B&K in Cuyahoga Falls

Address: 737 Munroe Falls Ave.

Hours: 11 a.m. to 8:30 pm. Tuesday through Saturday - now, all year.

Phone: 330-922-3355

See the stands Facebook page for specials.

New downtown eatery

Evelyns Coffee & BnhMi has opened at11 E. Exchange St., inthe space behind the Goodwill blue boutique on Main Street in downtown Akron.

The space previously housed coffee shops, including Wholly Joe.

So what is a bnh mi?

Bnh mi is the Vietnamese word for bread, and also in this case refers to the popular Vietnamese baguette sandwich (think sub sandwich on crusty, light bread), typically featuring a meat and pickled vegetables.

French colonists introduced the baguette to Vietnam, but the Vietnamese have made the sandwich their own, creating many versions.

At Evelyns, I enjoyed a chicken bnh that included pickled carrots, cucumber and cilantro ($5.50). You can also get a beef or meatball bnhmi.

Eveylyns also offers kimbap, a Korean dishof seasoned rice with fish cakes, carrots, egg and spinach rolled in seaweed. Other offerings include smoothies, papaya salad and a Vietnamese salad made with shredded cabbage, chicken, carrots and onion. It comes with a sweet and tangy dressing.

The shop offers Vietnamese iced coffee (made with sweetened condensed milk), along with a variety of other coffee drinks.

Vinh Nguyen, a local physician, opened the place this summer, taking advantage of the Start Downtown program operated by the nonprofit Downtown Akron Partnership. The program provides six months of support, including rent subsidies, in the 42-bock Special Improvement District in downtown Akron.

Evelyns is open from 8 a.m. to 4 p.m. Monday through Friday and 9 a.m. to 4 p.m. Saturday.

Phone is 330-849-5080.

See Evelyns web page --https://www.evelynscoffee.comfor more information and to order online.

West Side Bakery's Apple Week

This week is Apple Week at the West Side Bakery in Akron, celebrating 25 years in business this year.

Barb Talevich, who owns the bakery with her husband, Steve, said she expects to go through some fiveor six bushels of Golden Delicious apples from Bauman Orchards in Rittman to make a variety of apple treats.

Available now: Apple cobbler, apple hand pies, caramel apples, apple cobbler tea bread, apple coffee cake, cinnamon apple cheesecake and apple-frangipane galette (an apple tart featuring an almond pastry cream).

Apple fritters will be available this Friday and Saturday.

Its the only time of the year these fried treats are available.

Talevich happily reported that the bakerys employment roster is now back up to more than 20 full- and part-time workers.

For a time during the ongoing pandemic, she and and her husband were the only workers, and the shop was only open on Saturdays.

The shop, at 2303 W. Market St., is now open from 8 a.m. to 5 p.m. Monday through Saturday pickup only. Phone is 330-836-4101.

ThaiSoul Fusion Grill relocates

ThaiSoul Fusion Grill has moved to 992 Kenmore Boulevard in Akrons Kenmore neighborhood.

Thats the space that previously housed Lil Bit Cafe, which closed earlier this year. It apparently was not able to withstand the negative financial impact of the ongoing pandemic.

Well have more soon on ThaiSoul Fusion Grill, which, as its name suggests,offers Thai eats, as well as soul food.

Owners are Tawon and Patricia Burton. They most recently operated the eatery in Stark County, after running it out of space on Romig Roadnear the site of the former Rolling Acres Mall.

Phone is 330-937-8846. Online ordering is athttps://www.thaisoulfusiongrill.com.

The restaurant is only open for pickup at this time.

Wise Guys' clambake

Wise Guys Lounge & Grill in Akrons North Hill will offer a clambake from 3 to 9 p.m. Friday and Saturday.

Cost is $55 for clams, mussels, crab legs, potato, a half check, corn and clam chowder.

Add lobster for $10.

Guys, known for its wide selectionof wine, is at 1008 N. Main St. Phone is 330-922-3006.

Harvest Mart at Lock 3

Harvest Mart featuring food and non-edible items will debut at Lock 3 park off Main Street in downtown Akron on Saturday.

Itll run from 1 to 5 p.m. Saturday, and from 1 to 5 p.m. Oct. 24.

See the Harvest Mart at Lock 3 Facebook page for more information.

Akron'sJ Hudson, an experienced organizer of markets, is coordinating the event.

Hormone-free chicken, turkey, pork, lamb and beef, as well as pumpkins, gourds, apples, late-summer produce and more,will be available.

Cast your vote for favorite burger

You can vote for your favorite burger among two choices at Bob's Hamburg in Akron.

In its "Keeping Burgers Great 2020" election, you vote by buying the quarter pound burger with Swiss cheese and jalapenos or the burger with American cheese, ketchup, onions and mustard. A portion of each saleeach burger costs $6.35 will go to Akron Children's Hospital.

Voting continues through Nov 2. The winner will be revealed Election Day, Nov.3.

Bob's is at 1351 East Ave., near Interstate 76.

Last call at Louie's

As reported by Beacon Journal staff writer Alan Ashworth last week, Louie's Bar & Grille at 739 E. Glenwood Ave. in Akron's North Hill is closing this month. The 28-year-old Louie's, known for its burgers, cited COVID-19 restrictions in its decision to close.

Last day for customers is Saturday.

Thanks for the memories.

Send your local food news to Katie Byard at msakron@sbcglobal.net.

Read more from the original source:
Akron Dish: For first time, B&K drive-in staying open through winter in Cuyahoga Falls - Akron Beacon Journal

Monday, October 12, 2020

Dr. Michael Fine, Author

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Justice Brett Kavanaugh

The full audiobook can be downloaded here.

"Boys and girls like beer"

-- Brett Kavanaugh, Associate Justice, US Supreme Court

Every morning at 5 AM, three or four white minivans leave from a parking lot on Cowden Street in Central Falls, Rhode Island for factories all across southern New England. Each minivan is densely packed with 10 to 15 mostly undocumented immigrants who live two or three or five people to a room in the ramshackle wooden frame triple-deckers that are crammed into every available square foot in this old mill city. The people in the minivans are from all over the world - from Guatemala, Honduras and El Salvador, from Cape Verde, the Dominican Republic, Colombia; and Puerto Rico refugees from Hurricanes Maria and Dorian who cant find other jobs here. The vans are run by labor contractors who find and supply unskilled labor to the low-wage employers who need bodies for the hot, dirty, smelly and dangerous jobs no one else wants, in the factories, construction sites, meat-packing plants and fish-houses of Southern New England. The vans charge each worker $5 to $10 a day. The work pays minimum wage - $10.50 an hour in Rhode Island, $12.00 an hour in Massachusetts, $11.00 an hour in Connecticut. Theres lots of wage theft on these jobs sometimes workers only get paid for eight hours when they work 12 or 14, or get told the labor contractors havent been paid yet and then never get paid, or are paid piece work using a scale that means they earn $5 or $6 dollars an hour, when they were promised $20 an hour but youd have to produce at an impossible pace to generate that much income.

Yes, we drank beer. My friends and I. Boys and girls. Yes, we drank beer. I liked beer. Still like beer. We drank beer, said Judge Brett Kavanaugh during his testimony to the US Senate Judiciary Committee confirmation hearing.

This testimony provided a unique lens on American culture and mores. A preening conservative President, pandering to his base, chose an undistinguished juror to sit on the U.S. Supreme Court. The opposition party, powerless to stop Kavanaughs confirmation, used accusations about the nominees behavior in high school as the bulwark of their objections to his nomination.

By the time Judge Kavanaugh testified, the process of Supreme Court nomination and confirmation had already been defiled. The nomination to the Supreme Court of Judge Merrick Garland two years earlier had been blocked by the Senate Majority leader, just because he had the power to do that. This occurred just six years after a President had forced through health care insurance reform, because he had the power to do that. Health care insurance reform was unanimously opposed by a minority party, even though the reform itself was based on the ideas of that minority party, which objected only because it was in their perceived political interest to resist the reform, the hell with what the country wanted and needed.

Any pretense of government of, by and for the people, and of governing for the good of the nation had fallen by the wayside years ago. The U.S. Government has long been controlled by special interests, the consequence of the over-centralization of capital, itself a consequence of changes in banking and securities regulations that had been sought by the banking and securities industries themselves. The notion of a common good, of Americans as one people with liberty and justice for all was replaced by narcissism, consumer capitalism, and greed. Brett Kavanaugh is a shallow self-satisfied man - the pure product of a culture without compass or meaning. He now sits on our highest court, appointed for life. I worked hard, he said. I played basketball. I got into Yale and Yale Law School. I got ahead. And yes, I like beer.

These are the values we brought with us into a pandemic.

The nomination and confirmation of Brett Kavanaugh posed a simple question. In the words of another time - have we no sense of decency or responsibility to ourselves as a people?

The story of SARS-CoV-2 and of Covid-19 makes the answer to that question clear. We let loose a pandemic in the US that will cost at least 250,000 lives because we have lost our sense of dignity, our discipline, our courage and our pride.

Almost all the deaths from Covid-19 were preventable. Any fingers to be pointed must be pointed directly at us at ourselves, our culture and our politics. No one did this to us. We did this to ourselves.

Sometime in September or October of 2019, a bat, a pangolin or some other wild animal in China coughed, sneezed, or cried out, perhaps in pain from being caught or slaughtered, or just breathed near a human being. Out of that animal came a virus or more likely a thousand or more viral particles from the family of viruses called Coronavirus - that hung in the air for a moment. Then a human being nearby inhaled. The virus entered the nasal passages and perhaps the lungs of that person, an event likely happens millions or even billions of times a day.

The transfer of viral particles from animals and other human beings is a common, even trivial, event in the human experience. Those particles are always in the air we breathe and they are what our nasal passages, our lungs, our respiratory secretions and our immune systems work to protect us against almost always effectively. Most of the billions of viral particles we inhale or introduce into the body by touching eyes, nose or mouth have no significant impact on the health of individuals. Many viral particles that infect other species plant viruses, insect viruses, frog and toad viruses and bird viruses - have cellular architecture that is slightly different from the cellular architecture of human cells, so most of those viruses are unable to attach to human cells or cause infection. Most of those viral particles are quickly destroyed by the immune system. Most are just dust.

But the virus that entered a human body in the fall of 2019 was different. That virus, which likely evolved in another mammal, had a mechanism that allowed it to attach to specific proteins in certain human cells, cells that line the nose, are present in the lungs and heart and in small numbers in the gastrointestinal system, proteins that are called ACE2 receptors. ACE2 receptors are the proteins that allow the attachment of a hormone called angiotensin converting enzyme, a hormone that helps regulate blood pressure, among other functions.

The virus attached to human cells. It entered those cells and inserted itself into the genetic material of those cells, which is what viruses do. The virus then caused those cells to make copies of itself. Those copies destroyed the cell and were released into the bloodstream where they found and attached themselves to the ACE2 receptors of other cells and entered those cells and their genetic material. Those cells began making still more copies of the virus billions and billions of copies.

That human being had become infected. And then that human began to cough, or sneeze, or breathe or speak, so that the virus entered the air and infected other people nearby. And those people coughed and sneezed and infected other people. The newly infected people infected others, over and over again, until at least sixteen million people who have been tested and counted, as I am writing this, but very likely many more than that likely a hundred to two hundred million people - people who have had the virus but havent been tested or counted have become infected. Which is not many, really, when you consider that none of us has seen this virus before so have no immunity to it. And that there are seven billion of us. Likely all seven billion human beings are susceptible to this new virus and will become infected with it before long since none of us were immune to it in the fall of 2019.

Seven billion humans. 200 million people is about three percent of seven billion, so many more people will become infected before this pandemic is over.

I thought Id sit out the Coronavirus outbreak in the US as an observer. Im a fiction writer turned doctor turned fiction writer again. I worked as a family physician and then started doing public health in my late fifties. I was Director of the Rhode Island Department of Health 2011-2015 a period that included the Ebola epidemic of 2014-2015. Along the way Ive had the privilege of knowing three CDC directors, three Surgeons General (one of whom I helped train to be a state health officer, in 2015) and about 100 city and state health directors, a number of whom are close and dear personal friends with whom I talk frequently. I know CDC and its culture. Many friends and colleagues work there. And I also know government and how it works at the federal, state and city levels. Or doesnt.

When reports began to come out of China of hospitals overwhelmed, of a doctor who had been silenced and then died of the disease, of health workers getting sick and dying in large numbers, of people dying in the streets of Wuhan, I was writing in the morning, and working in the afternoons seeing patients two half days a week, and trying to develop new programs to reduce cost and improve access to health services in Central Falls, Rhode Island, the smallest, poorest and most densely populated city in the state. I consulted a little with the mayors of Central Falls and Pawtucket, Rhode Island, a neighboring city, but had turned my attention to writing fiction, an old first love. I worried a little about this new virus but I assumed that the Chinese CDC and WHO would get in front of it and get it stopped before it spread too far.

I didnt expect to find myself in the middle of one of the worst outbreaks of Coronavirus in the nation.

I also didnt expect the public health apparatus of the world and nation to so dismally fail. Or that the failure would reveal again what my 2018 book Health Care Revolt was written to reveal originally that we have a medical services market, a pharmaceutical products market and a health care insurance market but that we dont have a health-care system in the United States, a system that provides the same set of essential services to all Americans. Our medical, pharmaceutical and health care insurance markets are focused on profit, as markets should be, and not public health. These markets, and the profit focus of American society, have produced a culture in which the rich get richer and the poor are kicked to the side of the road.

Again. The poor get kicked to the side of the road. We have decades of data showing how the market focus of American health care has made our population sicker and poorer, worsened income inequality in the US and has disadvantaged the poor and people of color. You would have thought wed learned something from all our studies, and used what we learned to do a better job with Covid-19. Instead, we failed again, and failed so profoundly that we locked up our society for at least a year, and perhaps for as long as half a generation.

Still, because of my role with a community health center and with the two cities, I paid close attention to the stories and the data coming out of China in late 2019 and by January of 2020 was able to brief the mayors and my colleagues about what we were learning: This new Coronavirus is in the family of viruses that cause the common cold. This one likely evolved in bats and crossed over to human beings in the fall of 2019 in Wuhan China. It was related to the coronaviruses that cause SARS and MERS but this virus appeared to be harder to contain. In most people this new Coronavirus causes mild disease runny nose, fever, cough, loss of taste and smell, and sometimes nausea, vomiting, and diarrhea. But the new Coronavirus spreads quickly and can cause a very serious lung infection in some people, something called Adult Respiratory Distress Syndrome, which is much worse than a simple pneumonia and can be fatal in about one-third of the people who get significantly ill. The case fatality rate - the ratio of the number of people who get the disease to the number of people who die of it - was reported to be 3 percent, so that of a hundred people who would get the disease likely three would die, which made this Coronavirus 30 times more lethal than influenza but 20 times less lethal than Ebola, a virus that kills 50-75 percent of the people who get it.

Eventually wed learn the case fatality rate is more likely 0.4 percent or less, or about four times that of seasonal influenza. Even so thats a scary number, because every human being, in theory is susceptible to the Coronavirus, which means all of us could get sick at about the same time. In theory, a city of 100,000 might have 10,000 people in the hospital in the span of a few weeks, about ten times the usual number. And 3000, we thought then, would likely die. By comparison, about 5 percent of us are susceptible to seasonal flu each year. Even so, it kills 30,000 to 60,000 Americans every year. This means in that city of 100,000 people, likely 5000 people get the flu, and 500 people are hospitalized for it, and 5 die.

See the rest here:
What Was That? Coronavirus, Chaos and Democracy By Michael Fine PART 1 - GoLocalProv

Thanks to our ongoing global battle with the pandemic it looks like many nations will face some sort of covid-19 lockdown for the next six months a least. And given that for many of us it feels like restrictions had no sooner been lifted than they were reimposed, the result can be hard to bear psychologically, even if (thankfully) were unaffected physically.

However, help is at hand if you want to handle lockdown with the resolve, resilience and inventiveness of a ninja, take a look at these 7 ways to adapt to Covid-19 lockdown life.

You can literally learn to be a ninja online by watching free Ninja Learning Network training videos however please be careful not to injure yourself and seek advice from a physician before starting any strenuous fitness regime.

Been meaning to try that healthy vegetarian or vegan diet for some time? With so much plant-based food available online, theres never been a better time to switch your waistline will also thank you for it!

Creating some calm headspace for yourself is more important than ever during lockdown. If you dont want to adhere to Buddhist meditation practices, mindfulness is an effective secular version youll find on apps like Calm.

Always had a penchant for writing but never had the time to write down your thoughts? Writing a daily journal can be very therapeutic and your finished draft might turn into an autobiography or novel. Your lockdown diary could become a classic like Hagakure, still read hundreds of years after it was penned who knows?

Forget informal MOOCs where you put in the effort to study but dont get a recognised qualification in return take an online degree with ARU Distance Learning in a subject like digital marketing or psychology and you could be on your way to an exciting new career.

Being stuck indoors with family need not mean that youre at each others throats in fact it can be the ideal opportunity to build bridges and spend some quality time together. Spend a little less time on your phone or tablet and a little more time bonding over activities like cooking, crafts and simply chatting, then youll feel closer than ever to your loved ones.

Participating in a regular virtual pub quiz can be a great way of exercising those little grey cells and catching up with friends over a few convivial drinks. If youre struggling for ideas on how to get started, take a look at the amazing Jays Virtual Pub Quiz, which has taken the online world by storm this year!

Follow these seven ways to adapt to covid-19 lockdown life like a ninja and youll navigate the next few months like the most nimble shinobi you can thank us later!

Share youre lockdown tips in the comments section we would love to hear them.

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7 Ways To Adapt To the Covid-19 Lockdown Life Like A Ninja - Chiang Rai Times

Are you stressed, anxious, or depressed? Do you have trouble sleeping? Do you have skin and hair problems? The answer to all those queries can be CBD.

Cannabidiol, widely known as CBD, comes from cannabis plants and is one of the two prevalent compounds popular within the medical community. The other one, known as Tetrahydrocannabinol or THC, is responsible for the feeling high and the euphoric experience people experience.

Cannabis plants have two subspecies known as Cannabis Indica and Cannabis Sativa. Marijuana and hemp are both varieties of the Cannabis Sativa species, and CBD can be derived from both of them. Usually, hemp plants have been selectively bred and used industrially to remove THC almost completely. Marijuana, however, contains 30% of THC.

The breeding of hemp plants and CBD manufacturing has been legalized for medicinal reasons as long as it contains no more than 0.3% of THC per dry weight. CBD derived from marijuana is also legally manufactured but usually requires a doctors prescription to be sold.

CBD derived from both marijuana and hemp plants is used to treat many medical issues such as nausea (from chemotherapy), stress, anxiety, pain management, and treating muscle spasms that can be brought on due to multiple sclerosis, etc. It works on the neurotransmitters and regulates the nerve cells in our brains and tells them to calm down. This year, with the coronavirus pandemic going around, many people are stressed and have a heightened anxiety level than before for staying at home for too long or from losing jobs. It brings a feeling of relaxation to the patients who suffer from these issues and helps them sleep and relax. Another use of this compound is it is excellent in reducing acne and improves skin and hair conditions.

Products containing CBD are everywhere now, in hair products, skin products, capsules, oil, pet products, etc. It was also included in some food items as additives until the FDA banned it in 2019.

However, for ingesting, there are different methods that you can use that would best suit your needs. You can try inhaling, vaping, taking capsules orally, or ingesting oil drops. You can even choose what type of flavor or aroma you prefer.

The most effective relaxant that promotes the wellness of health is CBD-containing oil supplements. If you are new to using this, you can start with a low dosage and increase it as you see fit. Labels stating CBD oil have a significant amount of CBD not to be confused by hemp oil, which doesnt contain any CBD. You can buy CBD oil UK and notice how it boosts your mood and relaxes you.

Its simple. These oils come with an ml dropper and labeled instructions on how much dosage should be taken. It is usually recommended to start low, about 5mg, and then making your way up. Drop 5mg of oil under your tongue and keep it that way for around 60 90 seconds and then swallow. This way, you can retain the full potency of the product. Another thing to remember is that CBD oil drops can be taken after every six to eight hours. Ideally, you should use cannabinoids in consistent doses.

Side effects due to ingesting CBD have not been reported yet, or they are so mild that it was not directly attributed to cannabidiol. The ones reported were mild dry mouth and thirst, although they are not proven to be caused by CBD.

With the arrival of a pandemic and lockdown situation, most people have become anxious, depressed, and stressed financially and mentally. Some opt to take marijuana or other drugs and leave their problems behind, but the compound itself is so addictive that people keep asking for more. So when they finally decide to quit, they go through severe withdrawal issues. CBD has been known to help patients like these and manage mental health issues such as psychosis.

If you have skincare issues such as eczema and psoriasis, then using CBD topical products has been known to reduce oil production and eradicate acne. It contains anti-inflammatory agents that help in clearing out the skin.

CBD also helps with back pain or injury that involves inflammation; however, more studies are yet to be conducted.

As for stress-related issues, CBD has proven to relax the nerve cells and signals the body to take it slow. It acts as a mood regulator and reduces anxiety, hence re-balancing a persons mental and emotional health.

CBD therapy has also been shown to help health-care workers in this pandemic by providing relief to their neck or back pains and aid in restoring their sleep. It also helped many people who had panic attacks and were suffering from depression and the insomniacs affected due to the ongoing lockdown situation.

CBD reacts differently in men and women, where the latter is usually sensitive to the chemical compounds effects due to their hormone, estrogen. Women can develop a tolerance level within their bodies, so they must take a break now and then. A break from CBD will ensure their endocannabinoid system resets and help them adjust better to the product.

Despite CBD showing promising results, it is always good to consult your physician before making CBD a part of your life. It is particularly crucial to consult your doctor if you are taking other medications for your health issues such as antidepressants, which may have a side effect if combined with CBD.

CBD, with its therapeutic benefits, taken in appropriate amounts can lead to a better and healthier lifestyle, mentally, emotionally, and physically. However, a relationship with this compound requires you to put in a bit of work and make your life easier in this lockdown situation.

Read this article:
How Effective is CBD for your Health - Oregon Cannabis Connection

An appeal has gone out to help an 11-year-old girlwho needs a stem cell transplant from a stranger, to give her a second chance of life.

Arya was diagnosed with a rare blood disorder. But following a diagnosis of aplastic anaemia, a serious condition that occurs when the body stops producing enough new blood cells, she will also be starting immunosuppressant treatment.

This means her immune system isn't working as it should, putting her at a greater risk of infections.

To cure her aplastic anaemia Arya needs a lifesaving stem cell transplant. Blood cancer charity Antony Nolan is searching the worldwide stem cell registers for a donor whose tissue type matches Arya's and who is willing to donate their stem cells to help her live a normal life again.

However, the search for a perfect match is difficult for people like Arya, who is half Indian, with mixed ethnicity so she is sharing her story with Anthony Nolan in order to raise awareness of the need for more people of mixed race to join the stem cell register.

She said, "'They said it would be hard to find a donor for me because of my ethnicity but it isn't impossible. There is hope."

The best possible match for Arya is most likely to have the same background or mix of ethnicities. Currently, people with mixed Asian or other minority backgrounds have a 20% chance of finding a match from an unrelated donor, compared with nearly 70% for people with white, north European heritage.

Arya was diagnosed earlier this year and is receiving treatment at St Mary's Hospital, London.She added, 'When I first became unwell, I remember getting a stomach ache. At first it felt like a stitch but the pain didn't go away so I had more tests.'

These tests revealed something more serious. Arya's mum Brundha recalls: "Arya has always been fit and healthy, but life changed very quickly; all of a sudden we were talking to doctors about aplastic anaemia and Arya has had to stop many of the things she liked doing because her platelets, the tiny blood cells that help your body form clots, were low."

The family were given news of the treatment Arya would need to undergo and the need for a suitable donor.As the search continues, waiting for a match for Arya has inspired the Lloyd family to share their story. Their aim is to raise awareness of the need for more stem cell donors of mixed ethnicities to join the Anthony Nolan register and so increase the likelihood of finding a match for young people like Arya.

Brundha said: 'Because Arya is of mixed race, it was always unlikely we would find a match quickly. We have therefore started this appeal because we don't want to give up hope. It's a waiting game, but there could be someone out there who is a match. We also understand that younger people make better matches, so we would like to do all we can to make this more widely known.'

Aryas Consultant, Professor Josu de la Fuente, who is a Consultant Haematologist and Director of the Paediatric Bone Marrow Transplant Programme at Imperial College Healthcare in London said A well matched donor offers the best opportunity for Arya to establish normal blood production long-term and not to worry about the future.

"I will urge anyone, but particularly those of mixed ethnicity to consider joining the Anthony Nolan register so that no child with blood disorders faces an uncertain future: we can all contribute and be part of the solution.

Arya added: 'What stands out most for me are the bone marrow biopsies and being undergeneral anaesthetic for the first time.'

Rebecca Pritchard leads Anthony Nolan's work to recruit donors aged 1630 to its stem cell register. Rebecca says: 'Despite all she is going through, Arya is standing up to share her story in order to inspire people of mixed background to join the register. There is a potential lifesaver out there who could help her. If you're aged 1630 you can join the Anthony Nolan register online by completing a form and swabbing your cheeks with swabs we'll send in the post.

'Each time we're told a patient is in need of a transplant we'll check whether you're a match for them; if you're found to be a match you could give your stem cells to give hope to families like Arya's.'

Brundha said, 'We were unprepared for this and when it happens you want to know there is a source of donors for your child. That's why we're doing this to highlight the need. Being on the register could have a major impact on someone else's life. It's such an important thing you could do without realising.

"Families would be eternally grateful. You may never be called on, but if you are you could be a lifeline for someone. One person out there could be that person. It's a win-win for everybody.'

Arya added: 'The message I would like people to take away is Never give up hope and please join the register.

To find out more about joining the Anthony Nolan register, or to find out more about how you can support the charity click here

Original post:
'Never give up hope and please join the register' says 11-year-old in need of stem cell donor match - Asian Image

In the latest Stem Cell Banking market report, factors that are positively impacting the industry progression as well as the major threats & challenges existing in this domain are expounded. To unveil all the possible opportunities for business expansion, the study scrutinizes the regulatory and macroeconomic framework across the various geographies. It also delves into the competitive dynamics and evaluates how it will evolve during the forecast period. Further, it suggests strategies for dealing with the impact of the COVID-19.

Key highlights from COVID-19 impact analysis:

A gist of the regional landscape:

Request Sample Copy of this Report @ https://www.express-journal.com/request-sample/218931

Other highlights from the Stem Cell Banking market report:

Market Status:The complete details on Stem Cell Banking Market situation, principal regions, distribution channels, pricing structures are blanketed.

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Strategic Analysis Covered in TOC: - Key Topics Covered

Initially, the document offers an outline of the global market with a complete take a look at key drivers, constraints, challenges, traits and product types sold by using the employer. The file studies the Stem Cell Banking market capacity of key packages with the identity of forecast opportunities. The local evaluation with a focus on specific international locations and area of interest markets is presented. The pinnacle organization profiles with key-word market size and proportion estimation, revenue strategies, products, and other factors are studied.

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Stem Cell Banking Market to witness an impressive growth during the forecast period 2020 2025 - Express Journal

The global blood and bone marrow cancer treatment market was valued at $38.8B (approx 32.8B) in 2018 and is reportedly expected to reach $74.9B (approx 63.4B) by 2027, expanding at a CAGR of 7.7% from 2019 to 2027.

Blood cancer begins in the bone marrow which is the integral source of stem cells, which are later differentiated into different types of blood cells in the human body. Researchers have stated that approximately 1.85 million new cases of blood cancer will be diagnosed by 2040 throughout the globe.

These are the top global tech PR agencies you should absolutely check out in 2020

Europe holds a market share of 30.8% owing to the supportive regulatory framework provided by the European Medical Agency for the development and sale of medication for the treatment of blood cancer.

In the recent development, blood and bone marrow cancer treatment developer Priothera Limited, has raised 30M in its Series A round of funding led by Fountain Healthcare Partners with participation from co-lead investor HealthCap and funds managed by Tekla Capital Management, LLC, as well as EarlyBird Venture Capital.

According to the medtech startup, the raised funds will be used to progress the clinical development of mocravimod a modulator of sphingosine 1 phosphate (S1P) receptors, to enhance the curative potential of allogenic hematopoietic stem cell transplantation (HSCT) for treating AML.

Priothera expects to generate further randomised clinical data in high-risk AML patients with these funds.

Dublin-based Priothera was founded in 2020 by Drs. Florent Gros and Dhaval Patel. Joining the founding team include experienced industry executive, Dr. Christoph Bucher, Dr. Simone Seiter, and CFO Brice Suire.

The company claims to be leading the way in developing orally applied sphingosine 1 phosphate (S1P) receptor modulators for haematological malignancies. S1P receptor modulators have been suggested to largely reduce egress of T cell subsets from lymphatic tissues allowing for dual inhibition of graft-versus-host-disease (GvHD) and enhancing graft-versus-leukemia benefits in patients receiving allogenic stem cell transplant.

Allogenic stem cell transplant is the only potentially curative approach for AML patients but has unacceptably high mortality with current treatments, says Florent Gros, co-founder, and CEO of Priothera.

Florent Gros further adds, We are excited about mocravimod which has a unique mechanism of action and clinical proof of concept demonstrating its ability to improve survival outcomes for this devastating disease.

Acute myeloid leukemia (AML) is an aggressive and highly proliferative form of cancer where the bone marrow generates abnormal myeloblasts (a type of white blood cell). According to the company, AML is the most common form of leukemia in adults and can metastasise quickly if left untreated. This can typically lead to death within a few months of diagnosis.

Priothera has acquired rights to a drug called mocravimod from Japans Kyorin Pharmaceutical for the treatment of acute myeloid leukaemia.

According to the company, Mocravimod has already been extensively tested in multiple immunologic indications and has shown a survival benefit in an early clinical study evaluating acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) patients undergoing hematopoietic stem cell transplantation (HSCT).

Priothera is developing mocravimod in AML with the aim of enhancing the curative potential of Hematopoietic Stem Cell Transplantation (HSCT). The company claims that promising early clinical results have revealed that mocravimod has the potential to rebalance the patients immune system by decoupling Graft-versus-Host Disease (GvHD) from Graft-versus-Leukemia (GvL), preventing the first and preserving the latter.

Following the closing of the financing, people who have joined the Board of Directors include Florent Gros (Priotheras co-founder and CEO), Dr. Dhaval Patel (Priotheras co-founder and CSO at UCB), Dr. Manus Rogan (Fountain Healthcare Partners co-founder and MD), Dr. Marten Steen (partner at HealthCap), Dr. Henry Skinner (senior vice president at Tekla Capital Management, LLC) and Lionel Carnot (partner at EarlyBird Venture Capital).

Image credits: Jarun Ontakrai/ShutterStock

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This Dublin-based startup raises 30M to develop promising therapies for leukemia - Silicon Canals

Photo composition: Claudia Garca Martnez

Dr. Odalis Mara de la Guardia Pea, an expert immunologist, describes as "encouraging" preliminary findings obtained at the conclusion of the first phase of clinical trials evaluating the use of stem cells in patients facing lung damage caused by COVID-19.

The study, begun during the month of May at the Cuban Institute of Hematology and Immunology (IHI), was undertaken with a view toward eliminating or reducing interstitial inflammatory or fibrotic lung lesions following the infection.

The doctor, also an infectious disease specialist and head of External Services at the IHI, explains that the research will have significant impact "if, as we hope, stem cell therapy produces positive results in these patients with pulmonary alterations post-COVID-19.

"If the treatment is effective, it will be generalized across the entire country, improving the quality of life and respiratory capacity of these patients," she stated with the enthusiasm of someone devoted to the most important mission in the world: saving lives.

THE LUNG, THE "TARGET" ORGAN

De la Guardia Pea commented that, although SARS-COV-2 has a variety of dissimilar effects (cardiovascular, renal, cerebral, vascular, in distal or lower limbs, and others); the "target" organ in the case of COVID-19 is the lung, in which patients experience the most serious impact, both during the disease and once they have recovered, a pattern being studied internationally.

"We have detected cases, specifically in Cuban patients, who have presented this kind of affectation, especially those who have suffered symptoms over a longer period. Among those visited for the study, there were cases of important pulmonary alterations, which is the most frequent, but perhaps not the most serious," the specialist continued.

RECRUITMENT OF VOLUNTEERS

"These recruitment consultations were atypical, as they were done in the field, visiting the homes of recovered patients," the doctor explained, adding that potential volunteers needed to meet several criteria for inclusion in the clinical trials.

Those selected were between 18 and 70 years of age, of both sexes, who had contracted COVID-19 thirty days prior to the trial treatment, testing negative on a PCR at the time of recruitment, and exhibited respiratory symptoms since the beginning of the disease.

Specifically sought for the trials were patients who experienced a more torpid evolution of the disease, those who were hospitalized for more than 20 days, requiring oxygen, assisted ventilation, or the use of some aerosol as treatment, upon reaching serious or critical condition.

"More than 130 homes were visited over almost three months, from May to June; and 141 patients were interviewed, of which about 50 were studied. Twenty patients were included in the trial, which was the determined number," the doctor reported.

PULMONARY SEQUELAE

"During the investigation, several long term effects of COVID-19 were noted, although the most frequent involved the lungs. In some cases, indications of pulmonary fibrosis were detected, a condition that cannot be completely corrected, and can only be treated to increase lung capacity and improve quality of life," the doctor explained.

"The study is still in progress. The first phase has been completed, but there is some time remaining before final evaluation of the patients. What we can say is that, thus far, we are very happy with the results we have observed, they are encouraging," she emphasized.

UNFORGETTABLE STORIES

-Could you recount some stories that particularly impacted you?

-The first day I went out to recruit volunteers, I arrived at the home of a patient who, when she opened the door, exhibited obvious difficulty breathing, evident in plain sight.

We conducted the interview and learned that she experienced this difficulty on a daily basis, five weeks after being diagnosed with COVID-19 and 15 days after a negative PCR test.

This case was significant because we became aware of the lingering effects some patients face, who after having the disease, being discharged and completing all treatment, can have symptoms for a long time.

On another occasion, a patient received us effusively, grateful that he would continue to be treated, that he would receive some follow-up. This attitude was very common in many cases, confirming for us that the patients we visited were still feeling unwell, despite having recovered and been discharged from the hospital.

YOU CAN BE ASYMPTOMATIC OR YOU CAN DIE

"You can be infected and be asymptomatic, or develop the most severe symptoms of the disease and die. This is random, no one understands or can control it," the specialist warns, emphasizing the importance of being fully conscious of taking care of ourselves, since anyone can develop an aggressive case of COVID-19.

"I agree with everything Professor Durn says every day at nine o'clock in the morning, about how measures must be maintained and complied with: the use of facemasks, hand washing, shoe disinfection (with doormats soaked in 0.5% hypochlorite at the entrance to common areas), social distancing, and collective discipline.

"The population must take care; success in containing the pandemic lies in individual responsibility," she concluded.

STEM CELL TREATMENT

-When the patient is included in the study, treatment begins by injecting the granulocyte colony stimulating factor, Ior Leukocim, a product manufactured at Cubas Center for Molecular Immunology, to achieve the mobilization of stem cells from the bone marrow to the bloodstream.

-Subsequently, the patient's blood is extracted and mononuclear cells are separated and concentrated.

-This pool of cells includes hematopoietic and non-hematopoietic stem cells, which have immune-regulatory properties and promote the disappearance of lesions and the reconstitution of lung tissue.

-The cells are infused intravenously.

-The patient is evaluated one month following treatment and again at six months, to determine the clinical efficacy of the stem cell therapy.

Source: Granma interview with Consuelo Macas Abraham, director of the National Institute of Hematology and Immunology.

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Clinical trials with stem cells to treat effects of COVID-19 in the lungs advance - Granma English

How is the tool different from other editing systems? Is there a possibility of the tool being misused?

The story so far: The 2020 Nobel Prizes for sciences announced this week made history of sorts when one of it was exclusively shared by two women. Scientists Jennifer Doudna and Emmanuelle Charpentier bagged the Nobel Prize for Chemistry for the development of a method for genome editing. The discovery of one of gene technologys sharpest tools: the CRISPR/Cas9 genetic scissors will lead to the emergence of novel biological applications by making it easier to edit genes, and may make the dream of curing inherited diseases come true.

Much like what Microsoft (MS) Word does for writing, the CRISPR/Cas9 system allows for adding, altering and deleting the genomic code in living beings. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are pieces of DNA that bacteria snip off from viruses that once attacked them, much like file names used to store various documents we write in MS Word.

The COVID-19 pandemic has brought to the fore the importance of memory cells, which can quickly produce relevant antibodies to neutralise a repeat infection by a virus. Similarly, the CRISPR are a part of bacterias immunological systems that help them in recognising threatening viruses. When they sense a lurking virus, the bacteria produce customised RNA, which is necessary to translate DNA into protein, gleaned from the CRISPR libraries. This also contains Cas (CRISPR-associated) genes that are used to produce enzymes such as Cas-9. These enzymes the Cas-9 being a particularly popular one can be used to chop the DNA of the virus and destroy them.

Using the tool, researchers can change the DNA of animals, plants and microorganisms with precision. Emmanuelle Charpentier, who is now director, Max Planck Institute for Infection Biology, Berlin, had studied Streptococcus pyogenes, a species of bacteria known to be associated with a range of illnesses such as pharyngitis, tonsillitis and scarlet fever. While studying this, she discovered a previously unknown molecule, tracrRNA. Her work showed that tracrRNA is part of bacterias ancient immune system, CRISPR/Cas, that disarms viruses by cleaving their DNA, the Nobel release explains. Dr. Charpentier published her discovery in 2011. The same year, she initiated a collaboration with biochemist Jennifer Doudna, now a professor at the University of California, Berkeley.

Together, they succeeded in recreating the bacterias genetic scissors in a test tube and simplifying the scissors molecular components so they were easier to use, says an explainer on the Nobel Prizes website on their work. In a significant experiment, they reprogrammed the genetic scissors. In their natural form, the scissors recognise DNA from viruses, but Charpentier and Doudna proved that they could be controlled so that they can cut any DNA molecule at a predetermined site. Where the DNA is cut it is then easy to rewrite the code of life, the note adds.

Also read | What is genome editing

Other genome editing systems like TALENs and Zinc-Finger Nucleases can do similar jobs, but several users consider the Charpentier-Doudna tool more adaptable and easier to use.

It is less than a decade since this system gained wide research and commercial interest, but in the past few years, scientists have been able to make precise single-base-pair changes or larger insertions. Coupled with the availability of genome sequences for a growing number of organisms, the technology allows researchers to find out what genes do, move mutations that are identified and associated with disease into systems where they can be studied and tested for treatment, or where they can be tested in combinations with other mutations.

Editorial | Scissoring the DNA

The commercial potential of the system is so compelling that within years of its development, there was a battle over the ownership of the intellectual property rights of the CRISPR/Cas9 involving the University of California and the Massachusetts Institute of Technology's Broad Institute. The essence of this was that Feng Zhang of the Broad Institute had discovered a way to deploy the system in eukaryotic cells (that make up animal cells), whereas Dr. Doudnas patent application covered the process more generally. Dr. Zhangs patent was granted before Dr. Doudnas application. The patent dispute is still ongoing, and both sides claim victory in terms of the commercial application of the patents.

Also read | CRISPR-Cas gene editing causes crisper debates

The prize to CRISPR/Cas9 may be unusual as it is rare for a method to be announced and conferred a Nobel within a decade of its discovery, but it underlines its game-changing potential. In the last five years, both Dr. Doudna and Dr. Charpentier have been recipients of several important prizes in sciences.

Earlier this year, a person with hereditary blindness became the first to have a CRISPR/Cas-9-based therapy directly injected into her body. Gene-editing company CRISPR Therapeutics announced in June that two patients with beta thalassemia and one with sickle cell disease would no longer require blood transfusions after their bone marrow stem cells were edited using CRISPR techniques.

Earlier this week, according to a report in Chemistry World, Dr. Doudna launched a new company, Scribe Therapeutics, to begin work on treatments for amyotrophic lateral sclerosis. Reuters reported that Dr. Doudna is already employing CRISPR in the battle against the COVID-19 as a co-founder of biotech startup Mammoth, which has tied up with GlaxoSmithKline to develop a test to detect infections.

This year, the CSIR-Institute of Genomics and Integrative Biology (CSIR-IGIB) in Delhi developed a COVID-19 testing kit, nicknamed Feluda, after the fictional Bengali detective, based on the CRISPR/Cas9 system. There are commercial CRISPR-based home kits that allow amateur researchers to develop their own biotechnology applications, triggering a sub-culture called bio-hacking.

Also read | Change in ICMR rules stalls COVID-19 test kits from government labs

Research is already underway for using proteins that are smaller and more efficient than Cas-9, though the system purportedly holds promise for treating more complex diseases, such as cancer, heart diseases, mental illnesses, and the human immunodeficiency virus (HIV) infection.

The most controversial application of CRISPR/Cas9 was in 2018, when Chinese researcher He Jiankui announced that he had used it to create gene-edited twins Lula and Nana via in-vitro fertilisation. He used the gene scissors on the children when they were embryos to edit a gene, CCR5, that in its modified form would ostensibly protect the babies from HIV. The HIV uses the CCR5 to infect cells and the modified gene would shut the door against such an entry. He was widely condemned and sentenced to three years in jail, and stripped of his position at Shenzhen University, where he worked.

Also read | How safe is CRISPR?

While he broke a number of medical rules, what is particularly controversial is that the specific mutations that would supposedly protect the children from HIV were not achieved. There were a host of other unintended mutations too. It is not known how these mutations are going to play out over the children's lifetimes and whether they will spread to humanity more widely in due course. Thus, even though the CRISPR/Cas-9 system allows a democratic usage in labs across the world to tinker with genomes, it still has not reached the level of precision required to be sure that it does not cause unintentional side effects.

This year has seen a remarkable representation of women. Four women have been named Nobel Laureates in 2020 against five men so far. The Sveriges Riksbank (Swedens national bank) Prize for economics, or the 'economics Nobel', will be announced next week. The 2001-2019 interval has seen the maximum number of women Laureates 24 compared to just 11 from 1981 to 2000 and 7 from 1961 to 1980. There were only 12 women Laureates from 1901 to 1960. Only one woman, Marie Curie, has been honoured twice, with the 1903 Nobel Prize in Physics and the 1911 Nobel Prize in Chemistry.

Many women think that no matter what they do, their work will never be recognized the way it would be if they were a man, Al Jazeera quoted Dr. Doudna as saying. And I think (this prize) refutes that. It makes a strong statement that women can do science, women can do chemistry, and that great science is recognised and honoured.

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The Hindu Explains | How does a genome editing tool developed by two women scientists help in tackling diseases? - The Hindu