Archive for July, 2022

Theglobal cell therapy marketsize was valued atUSD 8.1 billion in 2021and is estimated to reachUSD 23.9 billion by 2030, growing at a CAGR of 14.5% over the forecast period. The development of precision medicine and advancements in cellular therapies in context to their efficiency & manufacturing are expected to be major drivers for the market. Moreover, the development of stem cell banking facilities and resultant enhancement of stem cells production, storage, and characterization are also expected to improve the volumetric capabilities of the market at a global level, which is anticipated to directly translate into revenue for this market at a larger level. Ongoing technological advancements in the parent and ancillary markets for stem and non-stem cells usage are expected to reinforce the demand over the forecast period. There are fewer commercialized cellular therapy products in the current market than the number of research products. This is partly due to stringent regulations and the high cost of stem cells.

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Cell lines, such as Induced Pluripotent Stem Cells (iPSC) and human Embryonic Stem Cells (hESC) are recognized as having high growth potential; as a result, many research entities and companies are making significant investments in R&D pertaining to iPSC- and hESC-derived products.

Pricing of stem cell transplantation varies from region to region. For instance, the cost of transplantation in the U.S. is higher than that in Germany or China. In March 2018, Alofisel by TiGenix received approval for marketing in Europe. This was the first allogeneic stem cell therapy to be approved in Europe. Furthermore, revenue for certain products varies for the country; for instance, products like INVOSSA received approval for marketing in Korea but have yet to receive marketing authorization in the U.S. Growth is also influenced by the commercialization of unauthorized stem cell treatments revenue generation.

Global Cell Therapy Market Definition

Therapy in which viable cells are injected, grafted, or implanted into a patient to effectuate a medicinal effect is known ascell therapy; for instance, In immunotherapy, T-cells capable of fighting cancer cells via cell-mediated immunity are transplanted, and stem cells are grafted to regenerate diseased tissues.

Cellular therapies hold a great therapeutic promise across various clinical applications. This has resulted in substantial global investments in research and their clinical translation. Rapid advances in stem cell research have the potential to fulfill the unmet demand of pharmaceutical entities, biotech entities, and doctors in disease management. Several unknown therapies are in clinical development.

Furthermore, government and private funding agencies are constantly offering grants to support projects at various stages of clinical trials, increasing the number of ongoing clinical trials.

Research on human embryonic stem cells is ethically controversial. Harvesting embryonic stem cells involves the destruction of human embryos, raising a moral concern. In addition, stringent regulations for obtaining Intellectual Property Rights (IPR) for products or materials used in research are major restraints for commercializing these services. Ethical approval should be obtained to store cell lines and tissues in biorepositories to avoid the usage of tissue for illegal purposes or to identify proxy diseases to claim insurance. Moreover, controversies surrounding the use of embryonic stem cells for research impede the market growth in several regions

The study categorizes the cell therapy market based on use type and therapy type at the regional and global levels.

The analysis of the cell therapy market is based on the use of stem cells for clinical and research purposes. The research-use segment dominated the market for the global cell therapy market and accounted for the largest revenue share of 58.3% in 2021. Currently, cell therapies (stem & non-stem cells) are majorly being used for research projects, which in turn, has led to a large revenue share of this segment in 2021. Cell-based therapies are all possibilities for the replacement, repair, restoration, and regeneration of damaged tissues, cells, and organs. As an alternative to traditional treatment strategies, researchers are investing heavily in developing effective and safe cell-based treatments.

As per the CGT Catapult database of clinical trials, 59 cell and gene therapy trials are ongoing in the UK. Out of all therapeutic areas, oncology has the highest number of ongoing clinical trials. T cells, CD34+ and CD133+ stem cells, mesenchymal stem/stromal cells are some predominantly employed cell types for clinical investigation. Neural cells, bone marrow mononuclear cells, fibroblasts, cornea cells, antigen-presenting cells, epithelial cells, and chondrocytes are some other cells that are being explored for the development of cell therapies.

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Asia Pacificaccounts for the highestCAGR during the forecast period

Based on the regions, the global cell therapy market has been segmented across North America, AsiaPacific, Europe, South America, and the Middle East & Africa.In the Asia Pacific, the market for cell therapy is anticipated to witness a lucrative growth rate of 15.5% over the forecast period. Advancements in stem cell therapy in Asian countries are observed to be better than those in the U.S. This has resulted in Asia leading stem cell research. Several stem cell consortiums in Asian countries aim to ensure coordinated and focused R&D programs. Moreover, patients from western countries migrate to Asian countries for treatment, owing to the flexible legal framework.

Companies from Japan, South Korea, India, China, Taiwan, Singapore, and the rest of Asia were active participants in the conference. In addition, the large regional population and untapped potential present in the region have resulted in global firms entering the market. Moreover, this region offers relatively inexpensive manufacturing & operating units for conducting research. These factors are expected to play a major role in expanding the stem cell market in this region.

The cell therapy market is mildly concentrated in nature with few numbers of global players operating in the market such as Kolon TissueGene, Inc., Anterogen Co., Ltd., JCR Pharmaceuticals Co., Ltd., Castle Creek Biosciences, Inc., MEDIPOST, Osiris Therapeutics, Inc., PHARMICELL Co., Ltd, Tameika Cell Technologies, Inc., Cells for Cells, NuVasive, Inc., Vericel Corporation, and Celgene Corporation.

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Cell Therapy Market With Manufacturing Process and CAGR Forecast by 2030 Designer Women - Designer Women

Returning home after a Fathers Day trip to New York City with his daughter in 2016, Scott Kesel thought he had come down with the flu. Bloodwork showed his blood platelets were lower than normal. He followed up with his regular physician and was given the news: he had chronic myelomonocytic leukemia (CMML).

CMML is a rare type of blood cancer that starts in the bone marrow, where blood cells are made. It can involve other areas of the body. There are only about 1,100 cases in the U.S. each year and its more common in people over age 60.

As a Canandaigua resident, Scott started his cancer journey at Wilmot Cancer Institutes Sands Cancer Center at F.F. Thompson. His oncologist laid out all the options: chemo and a stem cell transplant.

Knowing he would need a transplant, his team at Sands had him transfer to Wilmots Hematology team, where he began seeing Jason Mendler, M.D., and his transplant doctor, Omar Aljitawi, M.B.B.S.

He had chemotherapy at Wilmot, where he got to know the infusion nursing staff.

They have put a mindset in place thats so beneficial to the patient, he says.

For a stem cell transplant, his brother was the closest match they could find, although he was only a half-match. That left the option for a haplo-identical transplant available. Historically, it was required to have a closer match in order to do a transplant. With a haploidentical transplant, the donor is only half-matched. Its a newer procedure that is not available at all transplant centers, but the doctors at Wilmot have been performing the surgery since 2015.

He underwent the transplant but, unfortunately, in Scotts case, it didnt work.

For a short period, Scott went to another institution for a clinical trial. Unfortunately, that didnt work either. He developed pancreatitis and had to drop out of the trial. He also experienced cold agglutinin disease, which caused his immune system to attack his red blood cells. Cold temperatures can trigger it and he had to stay at Wilmot for about a month in a temperature-controlled room, set at 80 degrees at all times, to overcome it.

Once that resolved, the team at Wilmot suggested another treatment option to try on Scotts leukemia: a transplant with stem cells from an umbilical cord donation. Umbilical cord blood stem cells came from Australia and Spain to try to save Scotts life. He had only two cord blood units available and he needed both to have a successful transplant, which was his only viable chance to potentially cure his leukemia. Along with the cord blood, he also had radiation therapy with Louis Constine, M.D.

He had nothing but good things to say about the team that took care of him while he was hospitalized on Wilmot Cancer Centers sixth floor, the Blood and Marrow Transplant Unit.

It was exceptional. They were so friendly and accommodating right from the very beginning, he says. It wasnt limited to nurses. Theres medical technicians on the floor that were so friendly and became very good friends.

Scott Kesel (right) with Jason Mendler, M.D., at the 2019 Wilmot Warrior Walk

Thankfully, this time the transplant took. As of June 2022, Scott has been in remission for three-and-a-half years. He credits his team for getting him there.

Its an incredible group of people, he says.

But its not just his team hes grateful for. He appreciates that his life has returned basically back to normal, despite the tumultuous COVID pandemic that happened shortly after his transplant.

Hes gotten back to work and to hobbies he enjoys outside work.

I happen to be the worlds greatest tuba playing car salesman, he jokes.

This summer and fall, he has 28 gigs lined up, with different music groups around the region to keep him busy, and he looks forward to hunting and fishing during his free time.

For it all, he feels fortunate.

You have to be grateful for the outcome, he says. I got a lot of support remotely from people in my community who used the opportunity to promote bone marrow registration and blood drives, which was awful nice.

He adds, Im grateful that I ended up at Wilmot. I really couldnt have been in a better place.

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'World's Greatest Tuba-Playing Car Salesman' Bounces Back after Leukemia, Thanks to Wilmot Team - URMC

Preclinical evaluation of FasT CAR-T cellsFasT CAR-T (F-CAR-T) proliferation in vitro

To characterize the in vitro proliferative capacity of F-CAR-T cells, F-CAR-T and C-CAR-T cells were manufactured in parallel (Supplementary Methods, and Fig. S1) using T-cells from 6 B-ALL patients. To investigate the ex vivo proliferation of F-CAR-T, frozen CD19 F-CAR-T and C-CAR-T cells from each patient were thawed and stimulated with irradiated CD19-expressing K562 cells. The number of CD19-targeting CAR-T cells was then determined during the course of cell expansion in vitro. As shown in Fig. 1A, upon CD19 antigen stimulation, F-CAR-T proliferation was much more robust compared to C-CAR-T proliferation. On day 17 post co-culture, F-CAR-T expanded 1205.61226.3 fold (MeanSD), while C-CAR-T expanded only 116.437.2 fold (MeanSD), (p=0.001). To characterize the mechanism underlying the superior proliferative ability of F-CAR-T, we purified CD19+ CAR-T cells from both F-CAR-T and C-CAR-T. The expression of genes involved in cell proliferation, cell cycle, and apoptosis was analyzed using Nanostring (detailed gene sets are in Table S2). Gene expression profiles showed higher F-CAR-T expression scores for genes associated with cell cycle regulation (F-CAR-T vs. C-CAR-T, p<0.01) and lower expression scores for apoptosis-related genes (F-CAR-T vs. C-CAR-T, p<0.05) in F-CAR-T cells (Fig. S2A).

A Ex vivo cell proliferation of F-CAR-T and C-CAR-T derived from B-ALL patients (n=6) (***P=0.001, F-CAR-T vs. C-CAR-T, d17, unpaired student two-tailed t-test). B Tscm, Tcm, and Tem were characterized by surface staining of CD45RO and CD62L and analyzed with flow cytometry (***P<0.001 comparing F-CAR-T and C-CAR-T). C T-cell exhaustion was characterized by PD-1, LAG3, and TIM-3 staining; Statistical analyses of the percentage of PD1+ LAG3+ Tim3+ (***P<0.001, comparing F-CAR-T and C-CAR-T), unpaired student two-tailed t-test). D RTCA assay was used to examine the specific killing of HeLa-CD19 cells. Growth of target HeLa-CD19 or HeLa cells were monitored dynamically. E CD19+ target Nalm6-Luc cells or F Raji-Luc cells were co-cultured with either F-CAR-T or C-CAR-T for 6h. Target cell killing efficacy was calculated by luciferase activity. NS, P>0.05 F-CAR-T vs. C-CAR-T (unpaired student t-test, two-tailed). F-CAR-T FasT CAR-T, C-CAR-T conventional CAR-T, Tcm (CD45RO+CD62L+) T central memory cells, Tem (CD45RO+CD62L) T effector memory cells, Tscm (CD45ROCD62L+) T stem cell memory, PD1 programmed cell death protein 1, TIM-3 T cell immunoglobulin and mucin domain containing-3, LAG3 lymphocyte-activation gene 3, RTCA real-time cell analyzer, E:T effector cells: target cells, NT normal T-cell.

Phenotypes of unstimulated F-CAR-T from three healthy donors were analyzed by flow cytometry. The CD45ROCD62L+ population was 45.7%2.2% which was comparable to the un-transduced T-cells (data not shown). Upon stimulation with CD19+ tumor cells for 9 days, C-CAR-T central memory cells (Tcm, CD45RO+CD62L+ and effector memory cells (Tem, CD45RO+CD62L) were 56.62%11.97% and 40.48%9.70%, respectively, among the C-CAR-T cells (Fig. 1B and Figs. S2B and S2). In contrast, Tcm cells (87.92%4.36%) was predominant in F-CAR-T, with only a small fraction of Tem (7.84%3.79%). In addition, F-CAR-T cells demonstrated more abundant T stem cell memory (Tscm) (3.841.22% vs 2.342.48%, p<0.05) than C-CAR-T cells. We also examined the exhaustion status of the stimulated CAR-T cells. A higher percentage of PD-1+LAG3+Tim3+T-cells were detected in the C-CAR-T (11.19%2.54%) compared to F-CAR-T (3.59%2.51%, p<0.001) (Fig. 1C). Together these data indicated that the F-CAR-T exhibited a younger phenotype and was less exhausted compared to C-CAR-T.

We used a real-time cell analyzer (RTCA) assay to measure the cytotoxicity of F-CAR-T and C-CAR-T against CD19+ cells in vitro. F-CAR-T and C-CAR-T killing of Hela-CD19 target cells were comparable using this assay (Fig. 1D). Similar levels of IFN- and IL-2 production were also observed (Fig. S2D). In a luciferase-based cytotoxicity assay, CD19+ B leukemia cell lines, Raji and Nalm6, were both effectively killed to similar or better levels at different E:T ratios (Fig. 1E, F).

To compare the in vivo cytotoxicity of F-CAR-T and C-CAR-T, severe immunodeficient NOG mice were engrafted with Raji-luciferase cells. One week after the tumor grafts were established, F-CAR-T and C-CAR-T were intravenously injected at various doses. The engrafted tumors progressed aggressively in control groups with either vehicle alone or control T-cells (Fig. 2A). In contrast, F-CAR-T or C-CAR-T treatment greatly suppressed tumor growth in a dose-dependent manner (Fig. 2A). In the high dose group (2106/mice), both F-CAR-T and C-CAR-T eliminated the tumor rapidly. However, in the low dose group (5105/mice), F-CAR-T showed more effective tumor-killing compared to C-CAR-T. On day 20, mice in the low dose F-CAR-T group became tumor-free, while C-CAR-T treated mice exhibited tumor relapse (Fig. 2A). We examined the CAR-T cell expansion in vivo after infusion. As shown in Fig. 2B, both F-CAR-T and C-CAR-T began to expand in the peripheral blood 7 days after infusion. C-CAR-T cell numbers reached their peak on day 14 and receded on day 21. In contrast, the F-CAR-T cell number peaked on day 21 and declined to a baseline level on day 28. F-CAR-T not only persisted longer but also underwent 26 folds greater expansion than C-CAR-T (Fig. 2B).

A Raji-Luc cell engraftment NOG mice were given high dose (2106/mice, n=3) and low dose (5105/mice, n=3) F-CAR-T/C-CAR-T along with control groups. Tumor growth was monitored with IVIS scan once every 3 days; B CAR-T expansion in peripheral blood of mice was analyzed by flow cytometry (n=6). ***P<0.001 for F-CAR-T HD vs. C-CAR-T HD; F-CAR-T LD vs. C-CAR-T LD; F-CAR-T HD vs. F-CAR-T LD; C-CAR-T HD vs. C-CAR-T LD (two-way ANOVA statistical analysis); C Schematic of the Nalm6 (1106) xenograft model, CAR-T (2106) infused 1 day after cyclophosphamide (20mg/kg) treatment. Bone marrow infiltration of F-CAR-T was analyzed 10 days after CAR-T infusion (n=3); D CD45+CD2 F-CAR-T vs. C-CAR-T in peripheral blood of mice were analyzed by flow cytometry; *P<0.05 (unpaired student two-tailed t-test). IVIS in vivo imaging system, PB peripheral blood, i.v. intravenous, HD high dose, LD low dose, Cy cyclophosphamide; *p<0.05; #: number.

We examined the BM infiltration of F-CAR-T cells after infusion into Nalm6-bearing mice (Fig. 2C). A larger population of CAR-T cells was observed 10 days after infusion in BM in F-CAR-T infused group than that in the C-CAR-T group (p<0.05) (Fig. 2D), suggesting F-CAR-T cells possessed a better BM homing capability than C-CAR-T.

The chemokine receptor CXCR4 is known to be critical for BM homing of T-cells [25, 26]. Indeed, a higher percentage of CXCR4+ T cells were detected in F-CAR-T than in the C-CAR-T. Interestingly, this phenotype was more pronounced for CD4+ T cells than CD8+ T cells (Fig. S3A). In a two-chamber system, more F-CAR-T cells could be detected in the lower chamber than their C-CAR-T counterparts (Fig. S3B).

Between Jan. 2019 and Oct. 2019, 25 pediatric and adult patients with CD19+R/R B-ALL were enrolled onto our phase 1 trial, including two patients who had relapsed following a prior allo-HSCT. Patient characteristics are detailed in Table 1. The median age of patients was 20 (range: 344) years old. Twenty patients were >14 years old, and five were 14 years old. The median percentage of pre-treatment BM blasts was 9.05% (range: 0.1982.9%). As our pre-clinical studies demonstrated that F-CAR-T cells had a superior expansion capability as compared to C-CAR-T, we infused a relatively low doses of F-CAR-T cells, ranging from 104105 cells/kg: 3.0104 cells/kg (n=2), 6.5 (5.867.43)104 cells/kg (n=9), 1.01 (1.01.16)105 cells/kg (n=12), 1.52(1.471.56)105 cells/kg (n=2), (Fig. S4). The median time from apheresis to the infusion of CD19+F-CAR-T cells was 14 days (range: 1220). Although the manufacturing time of F-CAR-T was next day, the quality control time and detailed final product releases including sterility testing require a minimum of 710 days to complete. In addition, transportation of cell products requires approximately two days. Of the 25 patients who received CD19 F-CAR-T infusion, 22 (88%) received bridging chemotherapy between apheresis and lymphodepleting chemotherapy to control rapid disease progression (Table S3).

F-CAR-T cells were manufactured successfully for all patients. The mean transduction efficiency of F-CAR-T was 35.4% (range: 13.170.3%) (Fig. S5A). Both CD4+/CAR+ (mean, 49.6%; range: 13.673.2%) and CD8+/CAR+ (mean, 41.5%; range: 20.677.7%) subsets were present in the CD3+CAR+ T cell subsets of all products. The mean proportion of Tscm, Tem, and Tcm cells in the CD3+CAR+ T cell subsets of all products was 23.3% (range: 3.5545.3%), 33.2% (range: 17.267.9%), and 36.1% (range: 20.758.1%), respectively (Fig. S5B). F-CAR-T products exerted significant IFN- release and cytotoxic effects against the CD19+ cell line HELA-CD19 (Fig. S5, C, D).

All 25 infused patients experienced adverse events (AEs) of any grade, with 25 (100%) experiencing grade 3 or higher adverse events. No grade 5 events related to F-CAR-T treatment were observed (Table 2).

CRS occurred in 24 (96%) patients with 18 (72%) grade 12 CRS,6 (24%) of grade 3, and no grade 4 or higher CRS (Fig. S6). In the >14 years old group, 16/20 (80%) patients developed mild CRS, and only 2/20 (10%) developed grade 3 CRS. For 14 years old patients, 2/5 (40%) had mild CRS, yet 3/5 (60%) experienced grade 3 CRS (Table S4). ICANS was observed in 7 (28%) patients, with 2 (8%) grade 3 ICANS occurring in patients >14 years old and 5 (20%) grade 4 ICANS all occurring in patients 14 years old. No grade 5 ICANS was developed (Fig. S7 and Table S4). The most frequent presentation of CRS was fever, particularly a high fever of >39C. The first onset of CRS symptoms occurred between day 3 and 8 post-CAR-T infusion with a median onset at day 4 (range: 110 days). The most common symptoms of ICANS were seizure (5/7) and depressed consciousness (5/7). The median time to ICANS onset from CAR-T cell infusion was 7 days (range: 58), and the median time to resolution was 2 days (Fig. S7). All CRS and ICANS events were managed including early intervention when fever of 39C persisted for 24h. Sixteen (64%) patients received tocilizumab with a median total dose of 160mg (range: 160320mg). Twenty-one (84%) patients received corticosteroids including dexamethasone (median total dose, 43mg; range: 4127mg) and or methylprednisolone (median total dose, 190mg; range: 401070mg). The vast majority of these patients discontinued corticosteroids within 2 weeks. The change in IL-6, IFN-, IL-10, and GM-CSF levels after infusion are selectively shown in Fig. S8. The peak levels of these four cytokines were observed between day 710. Among all 21 cytokines examined, only post-infusion IL-6 levels were associated with moderate to severe CRS and/or ICANS (Figs. S9 and S10).

Superior in vivo proliferation and persistence of F-CAR-T compared to C-CAR-T cells were observed regardless of dose levels. The median peak level was reached on day 10 (range: 714 days) with 1.9105 transgene copies/g of genomic DNA (range: 0.225.2105 transgene copies/g of genomic DNA) by qPCR and 83 F-CAR-T cells per l blood (range: 42102 F-CAR-T cells per l blood) by FCM (Fig. 3A, B). No significant differences were observed among the different dose groups in the mean F-CAR-T copies peak (Fig. 3C). Importantly, there was no significant difference in the mean F-CAR-T copies peak between patients who received corticosteroids compared to those who did not (Fig. 3D).

A F-CAR-T cells in peripheral blood by qPCR. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; B F-CAR-T cells in peripheral blood by flow cytometry. Purple, dose level 1; black, dose level 2; blue, dose level 3; red, dose level 4; C Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood at each dose level. Statistical significance was determined by the MannWhitney test. D Comparison of the mean peak copy number of F-CAR-T cells in peripheral blood with or without steroids. Statistical significance was determined by the MannWhitney test.

Fourteen days after F-CAR-T cell infusion, all patients achieved morphologic CR including 2/25 with CR and 23/25 CR with incomplete hematologic recovery (CRi), which further improved to 11/25 CR and 14/25 CRi 28 days post F-CAR-T (Table 1 and Fig. 4). More importantly, 23/25 (92%) had the minimal residual disease (MRD)-negative remission on day 14 and day 28 after F-CAR-T treatment. Patients achieving remission through CAR-T were given the option to proceed to allo-HSCT. With a median time of 54 days (range: 4581 days) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status decided to pursue consolidative allo-HSCT including one patient who received a 2nd transplant. As of 18 October 2021, with a median follow-up duration of 693 days (range: 84973 days) among the 20 patients who had received allo-HSCT, one patient relapsed on day 172 and died 3 months after relapse, and four patients died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The other 15 patients remained in MRD-negative CR with a median remission duration of 734 days (range: 208973) except for one who became MRD-positive on day 294 with CD19+ disease. Among the other three patients (F05, F06, F16), one remained in MRD-negative CR on day 304, one remained in MRD-negative CR until day 303, received allo-HSCT but died from an infection on day 505, and one was lost to follow-up after day 114. Two patients who had MRD-positive CR after infusion withdrew from the study on day 42 and day 44, respectively, to seek other studies.

Clinical outcomes and consolidative allo-HSCT for the 25 patients who were treated with F-CAR-T therapy are shown. On day 28, 23/25 patients achieved MRD-negative CR/CRi. With a median time of 54 days (range: 4581) post F-CAR-T infusion, 20 of 23 patients with MRD-negative status received consolidative allo-HSCT. Among the 20 patients, 1 patient (F23) relapsed on day 172 and died 3 months after relapse. Four patients (F04, F09, F11, F12) died from transplant-related mortality (TRM) including infection (n=3) and chronic GVHD (n=1) on day 84, day 215, day 220, and day 312, respectively. The remaining 15 patients were in MRD-negative CR except for one (F18) who became MRD-positive on day 294. Among the other 3 patients (F05, F06, F16), 1 remained MRD-negative CR on day 304, 1 remained in MRD-negative CR until day 303, received allo-HSCT, and subsequently died from an infection on day 505. One patient was lost to follow-up after day 114. MRD minimal residual disease, CR complete remission, Allo-HSCT allogeneic hematopoietic stem cell transplantation.

F-CAR-T/T ratio in cerebrospinal fluid (CSF) was evaluated by FCM in 13/25 patients with available samples (Table S5). Between days 10 and 32, 9 patients were found to have considerable F-CAR-T penetration in their CSF, ranging from 40.65 to 79.2%, including 4 who developed severe ICANS. Among the other 4 patients, F-CAR-T cell abundance in the CSF ranged from 1.29% to 3.57%, and none experienced severe ICANS. Patients with higher levels of CAR-T in PB on day 10 consistently had higher levels of CAR-T in CSF with the exception of patient F15. Notably, CAR-T cells were still detectable in the CSF on day 101 with a 2.36% CAR-T/T ratio in patient F06, who also had undetectable circulating CAR-T cells at the same time.

In addition, concentrations of seven cytokines (IL-1b, IL-6, IL-10, IFN-, TNF-, MCP-1, and GM-CSF) in CSF samples from the above 10 of 13 patients were measured. Specifically, IL-1b was not detected in any of the 10 patients, and only one patient had detectable GM-CSF. For the other five cytokines, patients with severe ICANS had higher IL-6 levels in contrast to patients without severe ICANS, and the difference between the median level of IL-6 among these two groups of patients was statistically significant (Fig. S11). We did not observe significant differences among the other 4 cytokines between the two groups of patients. No clear relation between the CSF cytokine levels and the F-CAR-T/T % was observed.

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Next-day manufacture of a novel anti-CD19 CAR-T therapy for B-cell acute lymphoblastic leukemia: first-in-human clinical study | Blood Cancer Journal...

Ulcerative colitis, or UC, is a form of inflammatory bowel disease characterized by chronic and relapsing large intestine inflammation. Genetics account for only a minority of UC cases; hence, to develop treatments, researchers need to understand better the environmental contributions to this condition.

Gut microbes are in perpetual contact with the gastrointestinal tract, so they comprise important but poorly defined environmental variables contributing to UC development. Many studies have reported changes in gut microbiome composition in patients with UC compared to healthy individuals. While that suggests a potential role for gut microbes in UC pathogenesis, researchers have yet to pinpoint the causative microbes and associated bacterial proteins.

Dennis Wolans lab at Scripps Research is interested in identifying small-molecule activators and inhibiting bacterial enzymes involved in proliferation of human disease. Wolan said he was curious about what bacterial enzymes of the microbiome contribute to UC development.

Many publications have focused on the role of the microbiome in both health and disease states, he said. Most of these were focused on the taxonomical and phylogenic differences in the microbiome. But what about the associated bacterial proteins? What proteins are these gut bacteria making in disease conditions, and how are these interacting with the human body?

One protein of interest was serine proteases, a type of proteolytic enzyme that cleaves peptides at the serine amino acid. Researchers long have recognized that they coordinate many physiological processes and play key roles in regulating the inflammatory response. Previous studies have suggested increased proteolytic activity in microbial samples harvested from people with inflammatory disorders such as UC and Crohns disease.

Peter ThuyBuon, a graduate student and later a postdoc in the Wolan lab, led a project to study differential protein expression in healthy and UC fecal samples. He and the team described the project in a recent paper in the journal Molecular & Cellular Proteomics. In addition to standard mass spectrometry, ThuyBuon used a small molecular approach called affinity-based proteomic profiling to target and enrich for different types of proteases in the fecal samples.

We showed that there were 176 discrete host and microbial protein groups differentially enriched between healthy and UC patients, Wolan said. Furthermore, further enrichment of these proteins showed significantly higher levels of serine proteases in UC patients.

This finding has inspired exciting future research questions. For example, are elevated serine proteases the driver of UC or merely the effect of UC disease progression?

There is a lot of exciting work to be done using these findings, Wolan said. Future molecular studies should focus on how serine proteases might be contributing to UC and whether their levels can be manipulated to modify disease progression.

Functional proteomics has shown the potential role of serine proteases in UC. Future steps will include drug discovery and design of small-molecule regulators of bacterial enzymes.

Wolan said, Ultimately, the moderation of microbiome distribution in UC via external small-molecule intervention can serve as a foundation for UC prevention and treatment.

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Proteases implicated in ulcerative colitis - ASBMB Today

The very thought of getting someone elses poop transfused in your body may make you cringe but stool transplant has not only helped patients with gastrointestinal tract issues, it has also saved those who have had bone marrow transplants.

At Deenanath Mangeshkar Hospitals Centre of Excellence in Infectious Diseases and Department of Haematology, Pune, seven of the 11 patients of bone marrow transplants developed Clostridium difficile infection. They were treated with faecal microbial transplant (FMT), also referred to as stool transplant, over the past year.

Research worldwide has shown that a faecal transplant can restore healthy bacteria in the lower intestine which can help control Clostridium difficile or C. diff. According to the Johns Hopkins University School of Medicine, FMT can be more effective than antibiotics for keeping C. diff in check in some cases.

Since C. diff infection can recur and cause colitis (inflammation in the colon), FMT restores good and healthy bacteria, said Dr Parikshit Prayag, infectious disease consultant and in-charge of the Centre of Excellence in Infectious Diseases at Deenanath Mangeshkar hospital.

Dr Sameer Melinkeri, head of the department of haemotology at the hospital, said C. diff infection-related diarrhoea can occur in a normal setting in which antibiotics can be used for treatment. However, antibiotic treatment for recurrent infections can involve one or more courses of medication and their effectiveness comes down with each subsequent bout. FMT can arrest such infections post bone marrow transplant as it can be life-threatening, he added.

FMT is also done for certain disease conditions like Graft vs host disease (GvHD). Most people who undergo a bone marrow transplant suffer from blood cancer. Graft vs host disease can occur at any time after an allogeneic transplant where the donated bone marrow or peripheral stem cells can attack the recipients body. It can develop in the GI tract, skin or liver, Dr Prayag said.

Latest research published in the Journal of International Medical Research and others has shown how FMT is a promising treatment for patients with steroid-resistant GvHD. We have seen clinically relevant results in six of our patients, Dr Prayag said.

So, who can be donors? They are selected based on certain parameters. They should not be immune-compromised or have taken antibiotics over the past six months, says Dr Sampada Patwardhan, head of the department of microbiology at the hospital. Donor screening has to be done carefully. We need to rule out infections, she said.

Procedures on the transplant delivery methods may vary like colonoscopy and use of nasojejunal tube. The recovery may take a week or more and in most cases there are at least two weekly installations of the stool (in liquid form).

Very few centres conduct FMT and among them, the centre at Deenanath Hospital actively treats cases involving bone marrow transplants. At a recent virtual meeting of the International Society of Blood Transfusion, Dr Prayag made a strong case for encouraging stool transplants. The condition of C. diff is also underdiagnosed in the country as there isnt adequate infrastructure to correctly detect the problem, he pointed out.

In fact, FMT is being touted as a treatment option for many gut health issues. In an opinion article published on June 30 in the journal Trends in Molecular Medicine, a team from Harvard Medical School and Brigham and Womens Hospital (BWH) proposes that individuals bank samples of their own gut microbiota when they are young and healthy for potential use later in life in an autologous FMT.

A report in Science Daily quotes corresponding author Yang-Yu Liu, an associate professor of medicine at Harvard and an associate scientist in the Channing Division of Network Medicine at BWH, as saying, The idea of rewilding the human microbiome has taken off in recent years and has been hotly debated from medical, ethical and evolutionary perspectives. It is still unknown if people in industrialized societies can gain some health benefit by restoring their microbiome to an ancestral state. In this paper, we proposed a way to rejuvenate the human gut microbiome.

The report also listed OpenBiome, a non-profit stool bank based in Somerville, Massachusetts, as the first stool bank to offer an option for individuals to bank their own stool for future treatment of C. diff infection. Yang and his colleagues are now looking at if this treatment can be used for other diseases.

Conceptually, the idea of stool banking for autologous FMT is similar to when parents bank their babys cord blood for possible future use. However, there is greater potential for stool banking, and we anticipate that the chance of using stool samples is much higher than for cord blood. But there are many practical issues to implementing this idea, Yang is quoted as saying, hinting at optimal storage and cryopreservation issues.

Read the rest here:
Cutting Edge: Poop therapy can save your gut, and your life - The Indian Express

A non-nuclear mock B61-12 Joint Test Assembly (JTA) being prepared for test loading inside the B-2A Spirit stealth bombers bombs bay. (U.S. Air Force photo by Airman 1st Class Devan Halstead)

The U.S. Air Force recently released on the Defense Visual Information Distribution Service (DVIDS) website a series of interesting photos from Whiteman Air Force Base, Missouri. The photos, taken on June 13, 2022, show a high-fidelity, non-nuclear mock B61-12 Joint Test Assembly (JTA) being prepared for test loading inside the B-2A Spirit stealth bombers bombs bay. To our knowledge, these should be the first public photos of the weapon with the Spirit since testing aboard the aircraft has begun few years ago.

The Air Force did not provide many details and did not even mention the name of the bomb, simply stating the 72nd Test and Evaluation Squadron test loads a new nuclear-capable weapons delivery system for the B-2 Spirit bomber. The 72nd TES, a geographically separated unit of Eglin AFBs 53rd Wing based at Whiteman, is in charge of all testing and evaluation of new equipment, software and weapons systems for the B-2 Spirit stealth bomber.

It is not clear what the caption refers to with the term nuclear-capable weapons delivery system. The unofficial Nuclear Matters Handbook of the office of the Deputy Assistant Secretary of Defense for Nuclear Matters, gives us the following definition:

A nuclear weapon delivery system is the military platform and delivery vehicle by which a nuclear weapon is delivered to its intended target in the event of authorized use (by the President of the United States, who retains sole authority to employ nuclear weapons). Most nuclear weapons have been designed for a specific delivery system, making interoperability potentially challenging.

In addition to the mix of silo-based Minuteman III (MMIII) ICBMs, Trident II D5 Life Extension (LE) SLBMs carried on Ohio-class SSBNs, and B-2A and B-52H nuclear-capable heavy bombers, the U.S. nuclear force includes dual-capable aircraft (DCA), that can carry conventional or nuclear weapons.

Judging by this definition, the weapon delivery system in question should be the B-2A bomber, however the fact that the caption mentions the test loading aboard the aircraft might mean that this system is a new weapon rack inside the bombs bay designed to work with the new B61-12. Available public info states that the Spirit was designed to employ a Bomb Rack Assembly (BRA) for conventional munitions and a Rotary Launcher Assembly (RLA) for the delivery of conventional or nuclear weapons.

The BRA was later upgraded between 2003 and 2006 and became a Smart Bomb Rack Assembly capable of carrying as many as 80 independently targeted, JDAM GPS-guided weapons. So, since the new B61-12 in equipped with a guidance kit, it is possible that also the RLA is now being upgraded to use the new bomb. The new bomb variant will replace the B61-7 and B61-11 currently available for the B-2 fleet.

As we already reported, The B61 entered service 50 years ago and has undergone a Life-Extention Program (LEP) to consolidate and replace four legacy bomb variants, the B61 -3, -4, -7, and -11 mods, into the B61-12. The refurbished B61-12 will allow the retirement of the larger B83, becoming the only remaining gravity delivered nuke in the inventory. The bomb will carry a low-yield nuclear warhead with four yield options, reportedly 0.3 kilotons, 1.5 kilotons, 10 kilotons and 50 kilotons, instead of larger warheads like the models it is replacing (which can reach 400 kilotons depending on the variants).

The 12-foot, 825-pound bomb is designed to be delivered from the air in either ballistic or guided-gravity drop modes, thanks to a new Boeing-built tail assembly that includes an Inertial Navigation System (INS) precision-guidance package and two spin rocket motors that improve the bombs stability on its longitudinal axis during the descent. The LEP is said to be increasing the B61s accuracy so much (with a reported 30 m Circular Error Probability instead of the original 100 m) that it will have the same capability against hardened targets as the much more powerful weapons it is replacing.

See the article here:
U.S. Air Force Releases Photos Of Mock B61-12 Nuclear Bomb Test Loaded On B-2A Bomber - The Aviationist

Global Wellness Supplements Market Continuous Trend, Recent Events, Competitive Scenarios And Regional Forecast To 2029

DBMR added a comprehensive research document of 350+ pages on Global Wellness Supplements Market Share, Size, Industry Trends and Forecast 2029 with detailed insights on growth factors and strategies. Wellness Supplements report has been structured after a thorough study of various key market segments like market size, share, growth, demand, latest trends, market threats and key drivers which drives the market. Strategically analyzed facts and figures of the market and keen business insights covered in this industry analysis report would be a key aspect in achieving enduring business growth. The report offers steadfast knowledge and information of revolutionizing market landscape, what already exists in the market, future trends or what the market expects, the competitive environment, and strategies to plan to outshine the competitors.

Market Analysis and Insights: Wellness Supplements Market

The Wellness Supplements market is expected to witness market growth at a rate of 6.95% in the forecast period of 2022 to 2029. Data Bridge Market Research report on wellness supplements market provides analysis and insights regarding the various factors expected to be prevalent throughout the forecast period while providing their impacts on the markets growth. The rise in the awareness towards healthy lifestyles among the people worldwide is escalating the growth of wellness supplements market.

Wellness supplements are known to be substances that are projected to add further nutritional value to the diet for boosted health. Wellness supplements are vital for upholding a healthy life. Supplements contain all the minerals in sufficient amount to meet the daily need for the healthy life. Food supplement frequently contain calcium, folic acid, vitamin D and vitamin b12.

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Life Extension, OPTAVIA LLC, Beachbody LLC, Natures Sunshine Products, Inc., Organo Gold., Thrive Life, LLC, Phytoscience Trvo, Oriflame Cosmetics AG, Melaleuca Inc, Shaklee Corporation, Arbonne International, LLC., Forever Living.com, L.L.C, Juice Plus+, Herbalife International of America, Inc, and Isagenix Worldwide LLC, Nikken Inc., Wellness Resources, Inc., The Daily Wellness Company, Otsuka Holdings Co. Ltd, Glanbia plc, Nestle, Nuskin, and USANA Health Sciences, Inc.

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Academic Institutes, Clinical and Diagnostic Laboratories, Pharmaceutical and Biotechnology Companies and Others

3) Geographically, this report is located on several key regions with sales, revenue, and market share as well as growth rate of Wellness Supplements covered in these regions, 2021-2029.

Countries covered by Global Wellness Supplements Market are Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, China, Colombia, Czech Republic, Denmark, Egypt, Germany, Finland, France, Hong Kong, India ., Indonesia, Ireland, Israel, Italy, Japan, Malaysia, Mexico, Netherlands, New Zealand, Nigeria, Norway, Peru, Philippines, Poland, Portugal, Romania, Russia, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, Turkey, United Arab Emirates, United Kingdom, United States, Venezuela, Vietnam.

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Global Wellness Supplements Market Will Record Significant Revenue Growth During The Forecast Period 2022-2029 Designer Women - Designer Women

To remain effective in an era of near-peer warfare and to counter China's growing military, US Special Operations Command and the Navy SEALs are working on two new and improved mini-submarines that are expected to enter service soon.

The two new special-operations mini-subs the Mark 11 Shallow Water Combat Submersible and the Dry Combat Submersible will be the backbone of Naval Special Warfare's submersible fleet for decades to come.

The Mark 11 will replace the Mark 8 Mod 1 mini-sub. The new mini-sub comes with an increased operational range and payload, more advanced sensors, improved navigation systems, and a new command-and-control structure that will allow new technologies to be introduced more efficiently.

At 23 feet long, the Mark 11 will be able to carry six Navy SEALs: two crew and four combat divers. The mini-sub will be to dive to about 165 feet and will be flooded while in use, meaning the SEAL operators will be exposed to the elements and will have to use dry suits and oxygen tanks. (The British Special Boat Service has also ordered the Mark 11.)

SOCOM expects the Mark 11 to hit initial operating capability this summer. Should everything go according to plan, the new SEAL Delivery Vehicle will begin to phase out the Mark 8, which has been in service since the 1980s.

The Dry Combat Submersible is much larger and heavier. The 40-foot mini-submarine will have a vastly longer operational range and greater payload capacity than the Mark 11 and be more comfortable for the 10 commandos two crew and eight combat divers it will be able to carry.

At a recent industry conference, Cmdr. John Conway, SOCOM's program manager for special-operations forces undersea systems, likened the Dry Combat Submersible to "an electric truck" that can do a lot of things at the same time and can be adapted and improved with new sensors and systems in response to future threats and operational environments.

Naval Special Warfare is also looking at "other nontraditional ways to launch" the Mark 11, such as "a containerized solution" off of "some vessel of opportunity or things like that," Navy Cmdr. James Hanlon, SOCOM's program manager for special-operations maritime systems, said at the conference, according to Defense News.

In addition to the new Mark 11 and Dry Combat Submersible, Naval Special Warfare is working on a service-life extension program for the Dry Deck Shelter, which is attached to a submarine's hull and allows SEALs and other combat divers to exit and enter the submarine while underway.

The Navy's six Dry Deck Shelters were built between 1982 and 1991 and were expected to have service lives of 40 years. The planned extension would allow them to operate until the 2050s

The Navy SEAL teams are most well known for their direct-action capabilities. High-profile operations over the last 20 years, including the raid that killed Osama bin Laden, have fostered a belief that all that SEALs do is kick down doors and go after bad guys.

But SEAL teams have other capabilities and are proficient in many skill sets. The SEAL Delivery Vehicles are perhaps one of their most exotic capabilities, and the two SEAL Delivery Vehicle teams specialize in three mission sets: underwater insertion and extraction of special operations troops, underwater special reconnaissance, and underwater special operations.

In addition, SEAL Delivery Vehicle teams can support maritime counterterrorism operations by stealthily moving special operators close to a target that is in or near the water.

Generally, SEAL operators avoid an assignment to a SEAL Delivery Vehicle team because of the extremely difficult mission set. Although all Navy SEALs are combat divers, SEAL Delivery Vehicle team members take combat diving to the next level. Eight- to 10-hour dives are not uncommon.

Naval Special Warfare Command, which oversees the SEALs, has two delivery vehicle teams, which were first stood up in the early 1980s.

SEAL Delivery Vehicle Team One, now based in Hawaii, is dedicated to the West Coast and operations in the Pacific. SEAL Delivery Vehicle Team Two was deactivated in 2008 but reestablished in 2019 amid the shift toward great-power competition. SDVT-2 is based in Little Creek, Virginia, and is the dedicated delivery vehicle unit for the East Coast and operations in Europe.

The delivery vehicle teams are now part of Naval Special Warfare Group 8, which was created in 2020 through the consolidation of two other special warfare groups. The officer who led the group with the delivery vehicle teams was selected to lead Group 8 when it was formed, suggesting SDVs will have an important role going forward.

SEAL Delivery Vehicles are SOCOM's only special-operations submersible capability. In a conflict with China, mini-subs paired with the Navy's attack submarines would be ideal for getting SEALs into tough spots and denied areas, which will be essential for countering China's anti-access/area-denial umbrellaover the Western Pacific.

"Our relationship with our submarine force has never been closer," Rear Adm. Hugh Howard III, commander of Naval Special Warfare Command, told senators in May. "We see the undersea as absolutely critical to deterrence. I think that it is a place that we maintain advantage, and it is a place where we must maintain advantage to critically deter our peer adversaries."

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SOCOM is working on a new and improved Navy SEAL Delivery Vehicle - Business Insider

This is an audio transcript of the FT Weekend podcast episode: How to live forever

Lilah RaptopoulosHello FT Weekend listeners, its Lilah. Im away on vacation this week so weve reached into the vault to bring you one of our favourite episodes. My team and I talk about this episode a lot. Its about living forever and the ethics of radical life extension. Its also about defying death on this outrageous family summer vacation, which feels relevant for the season. One quick note: this episode first published in November. So in the beginning, when I say last year, I mean March of 2020. Okay, enjoy the show.

Did I ever tell you about the time Ira Glass almost gave me coronavirus? It was the last day of going about our normal lives in March of 2020, and everything was starting to shut down and my office was closing, so I packed up my laptop and my keyboard and some of my notebooks into these kind of unwieldy tote bags and I slung them over my shoulder and headed home. But my last stop was this one final interview with the iconic radio host in the studios of This American Life. So Ira and I sat together in the small audio booth for an hour, and we talked about the art of storytelling, and then I left. The next day his assistant emailed me to say that I might have coronavirus because Ira might have coronavirus because he had shaken hands with someone who had coronavirus. And I remember thinking, this cannot be how I go. And that was my first brush with mortality during the pandemic and the first of many. For the next few months, mortality and I became friends. We, like, encountered each other very regularly, going to the grocery store, passing a neighbour in the hallway, taking a walk. We all encountered it, all the time. There are some people who come face to face with death early because theyve had loved ones get sick and pass. And it happens more often to us as we get older. But these past 18 months, its been different. We have a new relationship with death. Weve had to face it either as a reality or as a real possibility.

[MUSIC PLAYING]

Lilah RaptopoulosThis is FT Weekend, the podcast. Im Lilah Raptopoulous. This weekend, were thinking about mortality. Do we look death in the face or do we avoid it altogether? Were going to the extreme ends. One of the worlds top climbers defies death by scaling treacherous mountains with his kids. And FT science writer Anjana Ahuja takes us through the science of living for hundreds of years.

[CLIP PLAYING]

Leo HouldingWhat did you do today, Jackson?

Jackson HouldingWe climbed up the Pingora Peak.

Leo HouldingWhich ones that? You point to it.

Jackson HouldingThat one.

Lilah RaptopoulosThats Leo Houlding, an outdoor adventurer and a guest writer for FT weekend, chatting with his four-year-old son, Jackson.

[CLIP PLAYING]

Leo HouldingWas it hard?

Jackson HouldingUmm, not very, but a bit.

Leo HouldingWas it were you scared at all?

Jackson HouldingNo.

Lilah RaptopoulosLeo recently took his family on a vacation that would leave most of us fearing for our lives. Thats them climbing up Pingora Peak, a mountain described by the first Europeans who saw it as impossible. It was a 14-day trek deep in Wind River Country in the wilderness of Wyoming. He and his wife, Jessica, took their two kids scrambling up isolated technical terrain. Theyre four and eight. Heres Leo with his daughter, Freya, climbing Wolfs Head, a 12,000-foot summit that would be hard for most adults.

[CLIP PLAYING]

Leo HouldingWhats happening, Freya?

Freya HouldingAh, well, Ive just gone up that ridge and Im, whoo! That ridge.

Leo HouldingAwesome. [Freya making sounds while climbing] There goes Freya, heading up that east ridge of the Wolfs Head. Pretty epic. One of the more epic features youre ever likely to see anywhere in the world.

Lilah RaptopoulosOn this trip, there was no cell service. They slept in tents and they brought all their food. Some of the climbing was almost vertical roped climbing and full harnesses. Leo talks about all of this in his piece, which Ive linked to in the show notes, but it sounded so outrageous that I wanted to talk to him about it.

Leo HouldingI think discomfort is underrated and our lives are so comfortable these days. Were all kind of obsessed with making everything as comfortable as possible, whereas actually a good dose of discomfort just makes you appreciate a little bit of comfort so much more.

Lilah RaptopoulosIt should be said that Leo is sort of a climbing celebrity. Hes considered one of the best in the world. You may have seen him. Hes been in documentaries like The Wildest Dream, an Imax film that documents a climb up Everest. And hes been on TV shows like Top Gear. Hes been to Antarctica twice to climb some of the most secluded mountains in the world. So it isnt just that he wants to torture his kids. He believes in this stuff for himself, too. So off they went into the wilderness, the whole family, and two unexpected hired hands.

Leo HouldingThe problem is to do that as a family of four, you need quite a lot of stuff. Aside from the climbing gear, you need all the camping gear, sleeping gear, cooking gear and, most of all, you need food for 14 days. Total was about 100 kilos of equipment. And thats where the llamas came in. (Laughter)

Lilah Raptopoulos(Laughter) Right. Okay. So in your story, youre talking about your van getting stuck and your kids being kind of like unsure about it and youre waiting for someone to help you out. And then this groan comes from the trailer behind you.

Leo HouldingNot many people know that llama trekking is a thing in the western states. There are a couple of outfitters who rent you llamas unguided. Theyre extremely easy animals to look after, unlike horses, which, you know, you kind of have to know stuff to handle horses.

Lilah RaptopoulosSo Leo, his wife, two kids, two llamas, 14 days worth of food and gear. They avoid a moose almost immediately as they get into the backwoods. And at this point, theyre going upwards, but not climbing just yet. On the walk to their camping spot, they meet a hiker who shows them an edible mushroom the size of a football. So they take that with them. And then when they set up camp, Leos wife, Jessica, casts her fishing rod out and immediately pulls back a perfect fish. Like in the movies.

At that stage, what were you thinking? Were you thinking, okay, were good. This is going to be an easy trip?

Leo HouldingI knew it wasnt going to be an easy trip because going into the backcountry is never easy. In fact, its very hard, but its simple. You know, you dont have all the complications of modern life. Its much more about shelter and food and looking after each other. I mean, we went into the Wind Rivers with a couple of objectives in mind, some big cliffs. But for most people that go there, they go there simply to experience the wilderness. Thats something that I would recommend to absolutely everyone.

Lilah RaptopoulosBut Leo and his family arent everyone. Jessica is also an experienced mountain climber, so on that third day, they take their kids out to climb some serious, bare-faced rocks.

Leo HouldingWe did this peak called Pingora, the east ledges of Pingora, which is Jacksons first big climb where he didnt get carried. And I mean, it is a big climb. Its 1,000 feet of climbing, but the face is 2,000 feet high. You kind of come in from the side. So its, its incredibly spectacular.

Lilah RaptopoulosThe following day, Leo takes Freya on a climb thats too hard for Jackson, so they go with one of his climbing buddies.

Leo HouldingIts definitely one of the best kind of easier climbs in North America, if not the world. Its this knife-edge ridge, you know, no more than a metre wide with pretty much 300m drops on both sides, outrageously exposed. Its quite complicated terrain. You have to squirm through chimneys and you have to rappel a bit and you have to go sideways. Going sideways in climbing is actually more difficult to protect than going straight up, and watching my little girl, she got scared, you know. Of course she got scared. But she faced her fear, she controlled her breathing and she absolutely loved it. She was just grinning from ear to ear the whole day.

Lilah RaptopoulosYeah, I have to say, as you tell the story, my heart is beating fast. I imagine that, like a lot of it. And tell me if Im wrong, that a lot of it is just deciding kind of not to be scared.

Leo HouldingThats a big part of it for sure. You know, kids, whatever you introduce them to is normal for them. So Jackson, whos only five, he was only four this summer when when we did some big climbs out in America. Hes just picking his nose, eating his sweets, looking at the birds, wittering away like any other four-year-old would in any other situation. Freya is extremely confident. Shes grown up in the mountains so shes way better than most adults in that terrain. In fact, we actually overtook a couple of adult teams and they were polite about it. But it must have been a little disheartening seeing a cute little eight-year-old skipping past you (laughter) on your big adventure.

Lilah RaptopoulosAll along, Leo had planned to go on an even more serious climb right at the end of their two weeks. Just him and his climbing partner. Theyre gone for just 24 hours. And when they get back nursing cramps and muscle spasms, they find out that the rest of his family had to fend off a bear. Did I not mention? The story also includes a bear.

Leo HouldingShe tried the old banging pans together to scare it off. She did have a kind of bear spray and a hiking pole, but it was snuffling around for, you know, a few hours through the night. And then she realised there was still some food in the pots, in one of these stuff sacks. So she gingerly pushed it out from underneath the tent and ironically, the noise of that scared it off.

Lilah RaptopoulosIf you have kids at this point, you might be asking yourself, is this a little too dangerous? Why is this guy putting his kids at risk? Going into the backcountry with two little kids is one thing, but treacherous climbs, foraged food, bears?

Leo HouldingI mean, theres no question that going into the mountains, going into the backcountry is dangerous. But sometimes people think of me as a professional climber, as an adventurer, as a risk-taker. But the truth is, its very much about risk management. Its about reducing the risks as much as possible. Any idiot can roll the dice a couple of times and get away with it. But when you do it professionally and you do high-risk stuff all the time, you have to do it with a very high degree of safety. But, you know, risk is an inherent part of all life, not just lives of adventure and life in the mountains. You kind of have to accept risk in life to be able to go out and make the most of it.

Lilah RaptopoulosBut Leo says thats the point.

Leo HouldingYou know, we had a couple of pretty serious storms and there was a lot of tears and screaming, as there is in many situations with kids. But actually, sometimes its the, its the low points, its the negative experiences which are the most memorable and most formative. Now, when you get to the top of the mountain, its all smiles and high fives and sunshine. Thats great. But when youre being pelted by hail, thats kind of leaving bruises. And, you know, my wife and I were literally stooped over the kids protecting them from this vicious hail storm. And thats when they learn, as we do, that, you know, you can survive, you can endure, you can push on through, dont give up. And you just have to kind of stay on top of the situation. And then when the sun does come out, you can dry off and live to fight another day.

[MUSIC PLAYING]

Lilah RaptopoulosAnd from looking death in the eye to trying to delay it forever. If you had the chance to undergo a therapy that would let you live for 200 years in your prime body, would you do it? Im talking 200 years in the body of a 35-year-old. Not just a longer life, but a longer life thats actually good. There are scientists working hard on making that possible right now, thanks in part to funding from billionaires like Jeff Bezos. But if Bezoss space launch was criticised for wasting money, how do we feel about his quest for eternal life? Should we consider it urgent medical research? Or is this just rich mans folly? Do we really want a hacker biology to live to 200? Think about it.

[MUSIC PLAYING]

Anjana AhujaYou know, if a woman could reset her biology and have the biology of a, you know, perpetually of a 30-year-old, then what happens to the concept of generations? Are we all going to be living you know, when we talk about multigenerational households, are we talking about instead of the three at the moment, maybe four, five, six?

Lilah RaptopoulosThats Anjana Ahuja, a contributing science writer for the FT. Anjana recently wrote the cover story for Life & Arts on this radical idea. It was called, Can we defeat death? And it asks just that. Can we actually live for hundreds of years or forever? And yeah, thats a real headline from a real newspaper, not a sci-fi novel, written by a real, distinguished journalist who actually has a PhD in space physics. So heres where we are. We arent close yet to making humans age in reverse. But scientists have been able to de-age cells in living organisms. There are mice that go blind from ageing. And we can manipulate their genes so that they can see again. Were close enough to a Benjamin Button situation that philosophers are now publishing books about the morality of extending the human lifespan.

So I cant stop thinking about your piece. (Laughter) Im just like, yeah, and Im wondering, like, where this started for you. Where did you start reporting it?

Anjana AhujaBack in September, I wrote a column about Altos Labs. I found out that it was being set up, it was being funded by Jeff Bezos. And to me, it seemed like a really serious outfit in terms of the money that was going into it, the people they were recruiting. And Ive always thought this, that actually somebody, sooner or later, is going to look at ageing as a technological problem because there is so much research into kind of interfering, trying to hack the ageing process.

Lilah RaptopoulosAltos is a Silicon Valley start-up and Anjana says it expands on the work of Shinya Yamanaka, a Nobel Prize-winning physiologist who heads Altoss scientific board. In 2006, Yamanaka made a discovery that some people consider even more important than the discovery of the DNAs double helix.

News clipThe Nobel Assembly at Karolinska Institute has today decided to award the Nobel Prize in physiology or medicine 2012 to Shinya Yamanaka.

Lilah RaptopoulosHis research showed that if you take an adult mouse cell and bathed in a mixture of four proteins, you can reset that cells age back to its embryonic state. In 2007, he proved that it could be done with human skin cells. Let me say that again. If you dunk individual cells in this particular cocktail of proteins, you can make those cells not just stop ageing. You can make them younger. And we, of course, are made entirely of cells.

Im curious what, like, the practical implications would be of these findings? Like, would it be just that individual parts of your body, those cells, could kind of Benjamin Button themselves backwards and yet you still would look old? Like, is there is there a way to sort of make the entire body young? Thats a very dumb question. But is there a way to make the whole body younger?

Anjana AhujaNo, its not a dumb question at all. I think thats really what these billionaires are hoping for, isnt it, to kind of freeze themselves in some kind of eternally youthful state? I think thats a very good question. The key is how you translate from individual cells up to whole organisms.

Lilah RaptopoulosThe name for what happens when you bathe cells in the Yamanaka Factor proteins is cellular reprogramming. Scientists try to reprogramme the cells of an entire body on mice, but when they did, the mice grew these horrible malignant tumours. Anjana put it like this. She said once you bring the cells back to their embryonic state, they lose their life plan. They dont know what to do next, so they grow into cancers. But there are companies right now working to see if you can apply these factors incrementally to de-age cells as far as you can without them developing cancer and then to do it again.

Anjana AhujaI suspect people will be quicker to apply it to individual organs first, individual tissues. You know, when you think about the number of people whose organs just wear out, they need transplants. So that might be an option.

Lilah RaptopoulosThis research, it isnt the only path to reverse ageing. A California scientist has been giving a small group of middle-aged men this cocktail of drugs that includes diabetes medication. Its made their thymus glands, which is a key part of the immune system, younger by two-and-a-half years. David Sinclair, a Harvard geneticist and one of the biggest names in anti-ageing. Hes doing a lot to experiment on his own body, including only eating one or two meals a day to put his body into survival mode. But Yamanakas discovery and where its going, thats whats really changing the game for longevity research. And to tell you the truth, thinking about it really pushed me on my assumptions about scientific progress, especially progress driven by Jeff Bezos.

These stories can look a little like the stories of men with too much money in Silicon Valley (laughter) just trying to like, kind of like, still be young and cool, right? Like, kind of suspend reality and like, isnt there something, even if its hard, comforting about the fact that we understand that, like, theres a limit to our lives and we understand the arc of it and, and we all die.

Anjana AhujaYeah, I mean, why dont these billionaires put their money to solving climate change and starvation and, you know, giving us clean drinking water and that kind of thing? You know, whats really interesting to me, I think, is when you think about what healthcare is.

Lilah RaptopoulosMmhmm.

Anjana AhujaIts about postponing death.

Lilah RaptopoulosYeah.

Anjana AhujaYou know, if you say to someone, you know, if you could not have cancer, not have heart disease, not have Alzheimers, not have dementia, if you could find a therapy that did that, would you take it? And I think there would be a lot of people that would say yes.

Lilah RaptopoulosMmhmm.

Anjana AhujaAnd what the scientists are saying, well, actually, you know, ageing is the common factor in lots of these diseases.

Lilah RaptopoulosMmhmm.

Anjana AhujaSo instead of, you know, kind of waiting till Alzheimers or heart disease or diabetes hits, why dont we make an upstream intervention and stop the root cause, or one root cause, which is ageing?

Lilah RaptopoulosAt the moment, though, most people seem to be sceptical of radical life extension. Anjana quotes the survey in her piece that only four per cent of Americans recently said theyd want to live past 120. Statistically, thats pretty close to no Americans wanting to live past 120. And Anjanas right! Part of that scepticism is that we cant imagine our world without Alzheimers, cancer and heart disease because the image we have is of old age as we know it now, one that is inextricably linked to disease and frailty and loneliness. But even if we could get rid of the negative consequences of ageing, if we can have lives that arent just longer but good till the end, should we? Have we really thought this through? What about the climate crisis and overpopulation and burning through our limited resources? What about marriage? Can you stay married to one person for 150 years? How many careers should we have over 200 years? What about dictators who dont ever die? Supreme Court justices? What about the House of Lords?

Anjana AhujaWhat do you do in the judicial system? You know, what does a life sentence mean, if youre living for 150, 200 years?

Lilah RaptopoulosYeah.

Anjana AhujaAnd just this idea that kind of a lot of institutions in society are set up with finite life spans in mind.

Lilah RaptopoulosAs we ended this conversation, I held two opposing feelings at once. One is, if this discovery happened today, it would be a nightmare on a macro scale, and we are not ready for it. And the other is, if I could give someone I love whos suffering from degenerative disease a pill to stop their pain or to reverse the damage, I would in a heartbeat, no question. And to not feel that way is kind of to be against progress.

Anjana AhujaI think there are some really important issues that may well become more important in the decades ahead. I dont know how close any of this is to fruition, this work about, you know, radical life extending. Could I live to 200? I dont know. And Im not sure that I would necessarily be able to make that decision today.

Lilah RaptopoulosYeah.

Anjana AhujaI think I would want to see what state the science was in, what state the research was in, what state I was in, and what kind of life I felt I could have, how I felt psychologically about it, what my family feel about it. You know, do they want me hanging around for a hundred years (laughter)?

Lilah RaptopoulosWould the people around you also be hanging around for an extra 100 years?

Anjana AhujaExactly. You know, we are going to get horribly bored with each other. So who knows? I mean, these are really big issues, but I hope that the piece is open to debate and we should talk about these things. Theyre always good because you never know how fast science is going to progress. Yeah. And sometimes, as weve seen with, you know, gene editing and CRISPR, sometimes these things hit before weve had a chance to think about them.

Lilah RaptopoulosMmhmm.

Anjana AhujaAnd I think its always really useful for us to just take a step back and reflect on how we live, how science might change things, and on what we feel comfortable with and, and, you know, the future of our species and our society.

Lilah RaptopoulosAnjana, youve given me so much to think about and probably our listeners too. Thank you so much for being on the show.

Anjana AhujaOh, its been my pleasure, Lilah. Thank you for having me!

[MUSIC PLAYING]

Lilah RaptopoulosAnd a final thought. We may be doing some of this life extension work already. We do live in a world of optimisation. We have apps to help us meditate. Our phones count our steps. We have strange little tools we attach to the back of our necks to help our posture. My watch tells me to stand up and breathe. My friends have a bed that heats up and cools down according to their optimal body temperature. There are start-ups that make vitamins specifically for your personal constitution. This isnt just scientists in a lab testing proteins on mice. This is kind of already happening.

Tiffany DarkeSo actually, what these tools, all the good tools for longevity that are coming into the market do is they help increase your health span as opposed to your life span.

Lilah RaptopoulosThats Tiffany Darke. Shes a regular contributor to the FTs luxury magazine, How to Spend It. She just wrote a piece on what the really rich are doing now to optimise their health. And shes pretty into it.

Tiffany DarkeIm a bit of a luxury junkie. Ive always, like, appreciated fashion. And I think that the science and the thought leadership around the luxury wellness industry has sort of increased exponentially in recent years.

Lilah RaptopoulosLets be clear. Living long is a luxury. The difference between being wealthy and poor can translate to living 10 or 20 years longer or shorter. And living long well, thats an even bigger luxury. In the UK, 20 per cent of mens lives are spent in poor health, a number thats increasing. And for women, thats even higher. Its 23 per cent. But for those that can afford it, there are a lot of new options. Were going to take you through a few of them here. The first is called RoseBar. Its a destination longevity programme and its marketing offers you a pretty bold promise.

Tiffany DarkeIt says a year from now, you can be younger. So they are promising reversal of ageing.

Lilah RaptopoulosThe RoseBar programme is a year-long programme. First they run longevity diagnostics and your bloodwork to see if youre on any negative health trajectories. And if you are, they put you on antidotes, which could be plasma treatments or even stem cell manipulation. From there, they give you fitness and diet advice and monthly check-ins. And the first programme launches this month at a resort in Ibiza. Its got a hyperbaric chamber, cryotherapy and IV facilities and literal shamans. Its like buying a souped-up life coach.

Tiffany DarkeYes, yes, life coach but with lots of kind of doctors and clinicians and all the sort of fun toys that surround the longevity industry as well.

Lilah RaptopoulosThe cost is, base, 15,000.

Tiffany DarkePlus the actual residential costs, plus getting there, plus the cost of the nutraceuticals, plus all the treatments.

Lilah RaptopoulosIf thats a bit too steep for you, theres a start-up called Thriva. Its an app that sends you a blood sample kit. The cost starts around $30 and can go as high as almost $200 per test, depending on your add-ons.

Tiffany DarkeIm warning you, its totally addictive. So you download this app on to your phone and then they send you a blood test and you do your blood test every three months. And its really easy at home, pinprick in the end of your finger.

Lilah RaptopoulosThey test what your doctor does at a normal check-up: your cholesterol, kidney and liver function, testosterone, vitamin levels. But they test it way more frequently and they put the results in an app, gamified. Next are the supplements. Lima sells supplements with nine scientifically backed ingredients: D3, keratin, ashwagandha, turmeric, stuff like that, but branded to look cool. You may have heard them referred to as the supermodel supplements: four pills a day, $300 a month, and you even get a luxe copper vessel to store them in.

Tiffany DarkeTheres a lot of hocus-pocus in the supplement market and, you know, a lot of good marketing, but actually there are supplements out there that do use good, patented adaptive medicines and at the dosages that your body needs to really thrive.

Lilah RaptopoulosWhich begs the question, are these just high-tech tools reminding us to do the obvious? Eat vegetables, avoid processed foods, take your vitamins, drink water, get sleep, exercise. Its all advice thats as old as time, but its a lot easier to follow when you can afford to get real-time data. And it doesnt hurt to have a shaman reminding you on a beach in Ibiza.

[MUSIC PLAYING]

Lilah RaptopoulosThats it for this week. Youve been listening to FT Weekend, the podcast from the Financial Times. Please keep in touch, say hi, tell me what you like, what issues you want to hear us explore. You can email us at ftweekendpodcast@ft.com. Were on Twitter @FTWeekendPod and Im on Instagram and Twitter @LilahRap. Ill put some photos of Leos family adventure on my feeds and, really, reach out. We love to put listeners on the show. In our show notes, as always, are links to everything mentioned. Theres also a special discount there on an FT Weekend subscription or even an FT.com trial. Weve got the best discounts collected for you in that link, which you can also get to at ft.com/weekendpodcast. Please leave us a review and share the show on your Twitter or Instagram story or with a few friends. This really is the best way you can help support the show.

Im Lilah Raptopoulos. Katya Kumkova and George Drake Jr are our senior producers. Lulu Smyth and Josh Gabert Doyan are our assistant producers, and Breen Turner is our sound engineer, with original music by Metaphor Music. Cheryl Brumley and Manuela Saragosa are our executive producers, and we have editorial direction from ReneKaplan. Well find each other again next week.

See the article here:
How to live forever - Financial Times

This is Geek Week, my newsletter about whatever nerdy things have happened to catch my eye over the past seven days. Heres me, musing about something I dont fully understand in an attempt to get my head around it: I imagine thats how most editions will be. If youd like to get this direct to your inbox, every single week,you can sign up here.

As is my right and privilege, I want to write an entire newsletter off the back of a single sentence I read in a BBC Futures article several months ago.

The article was this one: Apparently, its the next big thing. What is the metaverse? Its about (obviously) the metaverse: the idea of a virtual-reality internet where we all walk around inside a 3D world and have meetings and so on.

And the line that caught my interest was: Hype about digital worlds and augmented reality pops up every few years, but usually dies away.

This is the sort of thing that might end me up in Pseuds Corner, but: Scottish philosopher David Hume would have loved that sentence.

Hume pointed out (Im writing this from dusty memories of philosophy seminars in the early 2000s, so it wont be perfect, but I think its basically about right) that we never see one thing cause another thing. We see a thing, and then we see the next thing, and we infer cause. We see a billiard ball hit another billiard ball, and we see the other billiard ball move, but we never see one thing cause the other.

So how do we decide what causes what? For Hume, we have to use induction: if every time we see Event A, it is followed by Event B, but if we dont see Event A we dont see Event B, then we can start to think that A causes B.

But theres a problem with induction. Philosophers loved to prove stuff. All men are mortal; Socrates is a man; ergo Socrates is mortal, that sort of thing. All bachelors are unmarried. No power of two is divisible by three. These things are logical truths: If you accept the premises, you cant help but accept the conclusion.

That doesnt work with induction, though. You see the sun rise a thousand times, but you can never logically prove that it will rise tomorrow. The turkey notices that the farmer feeds him 364 days in a row, and is thus taken entirely by surprise on the 365th, when the farmer slaughters him and roasts him for Christmas.

Hume points out that you can only think of inductive reasoning in terms of probability. I think its likely that the sun will come up tomorrow: but I cant prove it, in mathematical/formal Aristotelian logic terms.

OK, so the metaverse. Hype about digital worlds and augmented reality pops up every few years, but usually dies away.

Every time you have seen the sun rise in the past, its risen the next day too. Every time the farmer fed the turkey, he fed it the next day too. Every time hype about virtual reality pops up, it dies away. But can you actually draw any conclusions from those things? After all, if you said The sun has always come up before, ergo I predict it will come up tomorrow, youd be making a correct prediction. If you said The farmer has always fed me before, ergo hell feed me tomorrow, youd be wrong (eventually, but importantly). Is Tech hype has always faded away before, ergo itll fade away again like the sun, or like the turkey?

Well, lets look at some other things. Video-calling technology is the obvious example. There was hype about that every few years. I learn from Wikipedia that it was first mooted in the 1870s, basically immediately after the invention of the telephone. The German Reich had closed-circuit television technology which allowed video calls in 1936. In the 70s AT&T released the Picturephone to great fanfare. In the 90s it started to work over the internet.

There have been various waves of hype about it. And each one died away, because the tech wasnt quite there, or it was too expensive, or not enough people had the kit to make it work. And you could reasonably have drawn the conclusion Hype about video-telephones pops up every few years, but usually dies away. And then the pandemic happened and suddenly a large percentage of us are doing it every day. No one is ever going to talk about video-calling hype again, because its just something we do and itd be weird to hype it in the same way itd be weird to hype, I dunno, bookshelves. Its just a technology that we have and that works and that is useful.

On the other hand, 3D glasses. Everyone thought that was the future of cinema, and then it died away, and then it came back (Avatar!) and then there was that brief 3D television thing, and that died away. And I dont think thats a product of the tech not being there polarised glasses are cheap, using two cameras instead of one isnt exactly ground-breaking stuff I think its that its basically a novelty, and the inconvenience and discomfort of having to wear the silly glasses outweigh the gains to your Viewing Experience of seeing things in 3D. Sometimes hype cycles really are just hype cycles.

Whats the difference between video-conferencing and 3D glasses? Whats the difference between the sun rising and the farmer killing the turkey?

The fundamental difference is one of theory. We have a really good theory to explain why we should predict the sun to rise tomorrow: Newtonian physics (we can do even better if we use relativity, but Newtons laws are fine). You predict that the sun will rise tomorrow because your theory says that the Earth spins on its axis once every 24 hours. That theory predicts lots of previous data, makes sense in the light of other theories, and generally seems pretty sound. Predicting that the sun wont rise tomorrow would mean rewriting a lot of what we think we know about the universe.

Whereas whats the turkeys theory for why the farmer is feeding him? Because he loves me and wants me to be happy, maybe, which is nice, but there are lots of equally plausible theories that could explain the data just as well.

The point is that you cant just look at the fact that there have been hype cycles and say from that that the thing will never happen. There have been AI winters before times when AI research stopped being fashionable, and funding into it slowed but I dont think there will be any more, because now AI is making people money. Theres a current hype cycle around fusion power, and maybe itll die away like the last several (fusion is 30 years away and always will be), but maybe one day itll just become profitable. [This thing] is coming and itll change the world will always be wrong every single time until its right.

So you need to look at the theory behind it and decide as best you can, not just on the hype cycle, whether you think its likely.

This isnt just true of new technology, by the way. Its true of disasters as well (every warning of an apocalypse will be false apart from one). Experts told us swine flu/bird flu/SARS/MERS would be a devastating global pandemic, and they were wrong every time, so we dont need to worry about this novel coronavirus.

There are various up-and-coming technologies that get repeatedly hyped and then die away again. Artificial general intelligence: people have thought that was on its way many times. Fusion energy. Life extension. Space colonies. Virtual reality.

For what its worth, I think true artificial intelligence and fusion energy probably will happen in the next few decades nature has proved theyre both possible (you can make an intelligent being out of neurons, you can make a fusion reactor in a star), obvious progress has been made towards them, and crucially people will be able to make lots of money out of both of them.

(Cheap energy is obviously valuable; really, really clever machines that can do exactly what you ask of them will have an incredibly wide array of uses if we manage to stop them from killing us all.)

Life extension seems to be plausible and, lets face it, rich people will pay for it once its available but super expensive, so I suspect theres a good chance of that happening. Space colonies are not likely to be profitable, but the worlds two richest people are interested in them and keep pushing money into technology that could make it happen, so I can see how that might happen.

And the metaverse I dont know. It always seems like a pain in the arse to me. The headsets are uncomfortable and I dont know if most of the use cases (conferencing etc) are so much better than a Zoom call that itd make it worthwhile. Maybe theyll get less clunky over time, but its pretty unlikely theyll ever get less clunky than a pair of 3D glasses. But Mark Zuckerberg obviously thinks its worth betting heavily on, and hes probably looked into it more closely than me.

But you cant know any of that just from looking at whether the hype has come and gone in the past. We do that too often. The climate has always changed! [So we shouldnt worry about it changing now.] Fusion is 30 years away and always will be! [So its not coming soon.]

Instead you have to actually look at the details. Its not enough to say that the farmer feeds you every day, so he always will. Sometimes Christmas happens.

Why do so many people believe things that are patently untrue? The point of believing things, surely, is to help us navigate the world: if there is a big hole in the ground in front of us, it is useful to believe that there is a big hole in the ground in front of us, so that we dont fall into it and break our legs. But lots of us all of us, probably believe things that are clearly untrue. A few that are probably relatively uncontroversial among Geek Week readers: astrology can predict your future; vaccines cause autism; there was a paedophile conspiracy involving Hillary Clinton run out of a Washington pizza restaurant.

(I dont know which of my beliefs are clearly untrue if I did Id stop believing them but it seems overwhelmingly likely that some of them are.)

Kevin Simler makes the case that beliefs have several roles. Some beliefs help us navigate the world. But others help us maintain social standing. Whether or not I believe in climate change will have very little effect on the actual outcomes of climate change, but it will have a huge effect on my ability to enjoy nice dinner parties in north London (or chats with rural Republicans in the American Midwest). He compares it to employees in a company in a corrupt, nepotistic town:

Consider the case of Acme Corp, a property development firm in a small town called Nepotsville. The unwritten rule of doing business in Nepotsville is that companies are expected to hire the city councils friends and family members. Companies that make these strategic hires end up getting their permits approved and winning contracts from the city. Meanwhile, companies that refuse to play ball find themselves getting sued, smeared in the local papers, and shut out of new business.

In this environment, Acme faces two kinds of incentives, one pragmatic and one political. First, like any business, it needs to complete projects on time and under budget. And in order to do that, it needs to act like a meritocracy, that is, by hiring qualified workers, monitoring their performance, and firing those who dont pull their weight. But at the same time, Acme also needs to appease the city council. And thus it needs to engage in a little cronyism, that is, by hiring workers who happen to be well-connected to the city council (even if theyre unqualified) and preventing those crony workers from being fired (even when they do shoddy work).

It might make sense to hire the mayors useless nephew, even though you know he wont pull his weight, because it will make your companys life easier. By comparison, it might make sense to believe things that arent true, as a signal that youre part of Team We Believe That Stuff. Sometimes those beliefs will actually be true.

Ive used relatively uncontroversial examples above. But I bet you could think of more mainstream beliefs that are clearly untrue (I cant face the row). And the real trick is to try to work out which of your own beliefs are held at least partly for crony reasons, because its just not plausible that there arent any.

This is Geek Week with Tom Chivers, a subscriber-only newsletter from i. If youd like to get this direct to your inbox, every single week,you can sign up here.

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Is the metaverse the next Zoom or the next 3D TV? Look beyond the hype - iNews

Twenty years ago, there wasn't all that much of a difference between the public view of rejuvenation research and the cryonics field. Both were mocked by the mainstream media, marginal areas of human endeavor out on the fringes of society, supported by very little funding and a handful of dedicated supporters. Yet in both cases, compelling research existed to support the goals - of the treatment of aging, of reversible cryopreservation - and was largely ignored, or even actively derided by the academic mainstream, worried about appearances.

A great deal has changed since then for the field of rejuvenation research. In the early 2000s, patient advocates were delighted and surprised by the rare occasion on which a six or seven figure check arrived from a philanthropist. It didn't happen often! Twenty years down the line, however, and billions in funding from philanthropists, research institutions, and venture funds are now devoted to the development of in vivo epigenetic reprogramming as an approach to the treatment of aging. Similarly, hundreds of millions have been invested in the development of senolytic therapies to clear senescent cells. The treatment of aging as a medical condition and the goal of reversal of aging is no longer mocked, it is taken seriously, and both funding and the number of ventures are increasing at a rapid pace.

How did this change happen? It was a mix of networking, advocacy, philanthropy, and compelling advances in the science, such as the development of the first senolytics and many consequent studies showing rapid, profound rejuvenation in mice. A tipping point was reached after years of a long, slow grind of bootstrapping: a little more progress, a little more support, a little more progress. Once past that tipping point, matters moved much more rapidly year after year, and the acceleration continues today.

I recently attended the 50th anniversary conference for the Alcor Life Extension Foundation, celebrating the lengthy run of one of the oldest cryonics providers. A good deal of the discussion there orbited around the usual questions asked by a small and passionate community: how does the cryonics field become larger, more robust? How does it achieve greater funding and faster progress towards widespread use? Fifty years on from the very early days of improvised equipment, ad hoc science, and regulatory opposition, the field of cryonics now looks a lot like the field of rejuvenation biotechnology did fifteen or twenty years ago. Slow progress is underway, the organizations are far more professional, and a few visionary philanthropists are putting in six or seven figure checks occasionally. Compelling advances in research exist, and are not receiving the widespread attention that they deserve. New organizations for advocacy and research are being founded with small budgets and big visions. Some of the technology waiting in the wings, such as reversible vitrification of human organs, may help to reach the tipping point once they are fully realized and in widespread use.

Given this, I would not be surprised to see the cryonics field becoming much larger and more commercial, growing suddenly and rapidly, in the mid-to-late 2030s. By that time, I would expect that reversible vitrification of organs will be a going concern, radically changing the economics and viability of organ donation, and adopted as a core enabling technology by the new industry focused on manufacturing patient-matched organs to order. The widespread recognition of this technological capability will bring many more people to the realization that cryopreservation on clinical death is a viable approach to saving lives that would otherwise be lost, and matters will proceed ever more rapidly from there on.

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When Will the Cryonics Industry Arrive at a Tipping Point in Growth ...

Walt Disney World reopens to the public after coronavirus closure

Walt Disney World has reopened to the public but with many new precautions to help prevent the spread of COVID-19.

USA TODAY, Wochit

In the decades following American animator and director Walt Disneys death in November 1966, pop culture conspiracy theorists have promoted a myth that his cryogenically frozen corpse is stored away in a hidden vault.

Over the years, the legend has taken different forms online. Some have speculated his frozen body is located under the Pirates of Caribbean ride, while others have claimed Disney named the movie Frozen sostories about his frozen head would stop showing up on Google.

Now, people are asserting that Disneys frozen body will be thawedin December in an attempt to resurrect him.

55 Years After His Death, Walt Disneys Frozen Body Will Be Thawed December 2021 In An Attempt To Bring Him Back To Life, reads a screenshot of a news headline shared to Facebook on Sept. 23 by the page Disney After Dark.

The post accumulated more than 1,700 shares and reactions in less than a day.The same claim has made its way to Instagram, blog pages and YouTube. On TikTok, a video about the article gained more than 92,000 likes in less than a week.

Fact check: Sony Group still owns Spider-Man film rights, despite online claims

But Disneys body isn't frozen. And the screenshot of the headline circulating online originated on a satirical website, which the posts fail to mention.

USA TODAY reached out to the social media users who shared the claim for comment.

The headline first appeared in a Sept. 15 article from Daily News Reported, which bills itself as a fabricated satirical newspaper and comedy website.

Daily News Reported uses invented names in all its stories, except in cases when public figures are being satirized, reads a disclaimer on the sites about page. Any other use of real names is accidental and coincidental.

The disclaimer is not included in the screenshots shared to social media.

Fact check: Image of bleeding Indigenous person at Met Gala is altered

It's an example of what could be called "stolen satire," where storieswritten as satire and presented that way originally are captured via screenshot and reposted in a way that makes them appear to be legitimate news.As a result, readers of the second-generation post are misled, as was the case here.

Dennis Kowalski, president oftheCryonics Institute a company that cryogenically freezes bodies and was mentioned in the Daily News Reported article- told USA TODAY the company is not bringing Disney back to life.

"We have heard of this rumor as well and we can confirm that it is not true," Kowalski said via email.

The claim that Disneys body is frozenisbased on the theory of cryonics, an experimental process in whichpatients bodiesare frozen with the hope that future technology will bring them back to life.

But scientists have criticized the cryonics industry and researchers say the theory is based on faith, not science.

"Reanimation or simulation is an abjectly false hope that is beyond the promise of technology and is certainly impossible with the frozen, dead tissue offered by the 'cryonics'industry," Michael Hendricks of McGill University wrote for MIT Technology Reviewin 2015.

Fact check: Claim that Biden is withholding benefits from unvaccinated veterans originated as satire

Regardless, Disney's body was notfrozen.His death certificate says he was cremated,the Los Angeles Times reportedin 2003. His ashes were interred at a family mausoleum at Forest Lawn Cemetery in Glendale, California, per PBS.

People close to Disney have also refuted the conspiracy theory.

There is absolutely no truth that my father, Walt Disney, wished to be frozen," Disney's daughter, Diane, wrote in her 1972 biography."I doubt that my father had ever heard of cryonics.

Based on our research, we rate FALSE the claim that Disneys body will be thawed in December to bring him back to life. The claim originated on a satirical website. Disneys body was cremated and his asheswere interred at Forest LawnCemetery in Glendale, California.

Thank you for supporting our journalism. You can subscribe to our print edition, ad-free app, or electronic newspaper replica here.

Our fact-check work is supported in part by a grant from Facebook.

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Fact check: Walt Disney's frozen body will not be thawed in December

What happened

The downtrodden biotech space has kicked off the second half of 2022 with a boom. Hard-hit gene-editing and gene therapy companies in particular have started the back half of the year on the right foot. Underscoring this point, Bluebird Bio (BLUE 6.97%) stock has already risen by 17% over the holiday-shortened week as of Thursday's closing bell, according to data provided by S&P Global Market Intelligence.

What's more, shares of CRISPR Therapeutics (CRSP 0.21%) have gained 22.6% over the same period, and fellow gene editor Editas Medicine (EDIT -0.20%) also saw its equity rise in price by a healthy 20.7% this week. By contrast, Bluebird and Editas shares both fell by over 50% over the first six months of 2022, while CRISPR's stock price stumbled by a noteworthy 20% during the first half of the year.

Image Source: Getty Images.

What's behind this sudden trend reversal? The most likely explanation is simply short-sellers covering their positions (buying back their borrowed shares). In keeping with this theme, Bluebird, Editas, and CRISPR all saw a sharp rise in their short interest during the first six months of 2022. Short-sellers piled into these three names earlier this year due to the fact that they are all cash flow negative, which is a tough spot to be in during a persistent bear market and an era of rising interest rates. Bluebird, in fact, is staring down a serious cash crunch at the moment.

Short-sellers, for their part, are probably backing away at this stage for no other reason than to play it safe in the event that big pharma starts to go bargain shopping.

Why might big pharma target beaten-down gene-editing and gene therapy companies in the second half of the year? The key reason is that these high-value fields are starting to move beyond the research stage of their life cycle and into the realm of commercially available therapies.

Speaking to this point, Bluebird's gene therapies for beta thalassemia and cerebral adrenoleukodystrophy appear to be on their way toward a formal approval from the Food and Drug Administration (FDA) following a pair of positive advisory committee votes last month. What's more, CRISPR is also expected to file for regulatory approval for its Vertex Pharmaceuticalspartnered blood disorder candidate, exa-cel, later this year.

Are any of these three biotech stocks still worth buying? CRISPR is arguably the most attractive bargain among the three. The company's ex-vivo gene-editing platform has posted stellar trial results so far, and Vertex could very well decide to buy its partner as a result.

Bluebird, on the other hand, is a tough call. The company ought to have a compelling buyout case if the FDA does grant it a pair of approvals soon. The bad news is that the biotech's balance sheet may force a sale at a heavily discounted price (relative to the commercial potential of its lead assets).

Finally, Editas might simply get lost in the mix when everything is said and done. There are several gene-editing companies vying for the spot of top dog, and Editas' clinical pipeline lags in several key areas at the moment. Time will tell.

George Budwell has no position in any of the stocks mentioned. The Motley Fool has positions in and recommends CRISPR Therapeutics, Editas Medicine, and Vertex Pharmaceuticals. The Motley Fool recommends Bluebird Bio. The Motley Fool has a disclosure policy.

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Why Shares of Bluebird Bio, CRISPR Therapeutics, and Editas Medicine Soared This Week - The Motley Fool

Can gene-editing technology CRISPR create new crops that help fight climate change as they grow? Thats what a group of researchers hopes to do with $11 million in funding from the Chan Zuckerberg Initiative. The funding will go toward efforts to enhance plants starting with rice and soil so that theyre better at trapping carbon dioxide. The effort, which was announcedlast week, is being led by the Innovative Genomics Institute, which was founded byNobel laureateand co-inventor of CRISPR Jennifer Doudna.

[Jennifer] and I saw eye to eye on climate and how big of a problem it is in the world. And we just didnt want to sit on the sidelines anymore, says Innovative Genomics Institute (IGI) executive director Brad Ringeisen.

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The rice genome is easier to manipulate than other crops, according to Ringeisen, in part because its already been studied a lot and iswell understood. One of the scientists involved in IGIs initiative is Pamela Ronald, whose research is widely known for leading to thedevelopment of rice varietiesthat tolerate flooding for much longer than other types using a different type of genetic engineering thats more likeprecision breeding. That rice is now grown by more than 6 million farmers across India and Bangladesh,according toRonalds laboratory at the University of California, Davis.

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Climate change-fighting rice? Plants trap carbon dioxide as they grow and CRISPR gene editing can optimize this process - Genetic Literacy Project

In a trio of studies published on June 27 in the journalNature Microbiology, researchers at The University of Texas at Austin have discovered "fingerprints" of mysterious viruses hidden in an ancient group of microbes that may include the ancestors of all complex life on Earth: from fungi to plants to humans.

Ths discovery is significant; it explores the hypothesis that viruses were imperative to the evolution of humans and other complex life forms.

These microbes known as Asgard archaea after the abode of the gods in Norse mythology are usually found in the frigid sediments deep in the ocean and in boiling springs, and existed on Earth before the firsteukaryoticcells, which carry theirDNAinside a nucleus.

Some scientists have hypothesized that viruses may have played in role in how life forms first came to be by infecting the Asgard archaea. They may have even given rise to some of the first precursors to the nucleus. But, no Asgard-infecting viruses had been discovered hitherto. The latest research by Ian Rambo (a former doctoral student at UT Austin) and other members of Brett Baker's lab sheds light on how viruses might have played a role in this billions-year-old history.

"These are the first studies investigating Asgard archaeal viruses; there was nothing known before," Susanne Erdmann, group leader of the archaeal virology research group at the Max Planck Institute for Marine Microbiology in Bremen, Germany, who was not involved in the studies, toldLive Science. In the future, this line of research may reveal if and how viruses were involved in the emergence of eukaryotic cells on Earth, she said.

In the new research, scientists searched for evidence of viral infection embedded in the DNA of Asgard archaea - which comes in the form of viral DNA called "CRISPR spacers."

According to Rambo, most people who think of CRISPR relate it to the famous gene-editing tool that allows scientists to easily manipulate genetic sequences. This tool was originally adapted from the natural defense mechanisms of bacteria and archaea.

CRISPR refers to a region of DNA made up of short, repeated sequences with "spacers" sandwiched between each repeat. Interestingly, bacteria and archaea swipe these spacers from viruses that infect them, and the cells maintain a memory bank of viral DNA that helps them recognize the viruses should they attack again.

"It's an adaptive immune system that remembers these previous infections," said Rambo, who is now a postdoctoral scholar with the USDA's Agricultural Research Service.

Rambo and his colleagues had hunted in the Guaymas Basin in the Gulf of California the body of water between Baja California and mainland Mexico for such DNA spacers in Asgard archaea specimens collected from sediments near hydrothermal vents, roughly 1.25 miles (2 kilometers) beneath the water's surface.

The team matched the spacers they found to longer stretches of viral DNA gathered from the deep-sea environment.

The researchers could infer the kinds of proteins the various genes code for and how the viruses might function, working with viral DNA.

But, eventually, they could only figure out the functions of some of the viruses' genes; the functions of the vast majority of the genes are still unknown, Erdmann said. Also, because CRISPR doesn't work against all viruses, many more Asgard-infecting viruses are yet to be discovered, she said.

These hidden viruses could be found by growing Asgard archaea in the lab. "However, culturing Asgard archaea has been proven very difficult," Erdmann said. Until now, only one research group has managed to culture Asgard archaea, and it took them 12 long years to do it as archaeal cells take weeks to replicate.

But until more Asgards can be grown in the lab, CRISPR spacer matching is probably the most efficient way to find more viruses, Krupovic said. As more viruses are found, their role in the emergence of eukaryotes, including humans, may gain more clarity, added Rambo.

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Newly discovered viruses can offer clues about the rise of complex life on Earth - Interesting Engineering

Male hypogonadism, also known as testosterone deficiency, is a failure of the testes to produce the male sex hormone testosterone, sperm, or both.

It can be due to a testicular disorder or the result of a disease process involving the hypothalamus and pituitary gland.

Hypogonadism can affect many organ functions and it can have a negative impact on quality of life.

The signs and symptoms depend on when it starts, how severe the deficiency is, and whether or not there is a decrease in the major functions of the testes.

A lack of testosterone can cause a wide range of symptoms.

These depend on:

Adolescents and young adults who have not yet completed puberty appear younger than their chronological age.

They may also have small genitalia, a lack of facial hair, failure of the voice to deepen, and difficulty gaining muscle mass, even with exercise.

Puberty-onset hypogonadism can lead to:

Symptoms of adult-onset hypogonadism include:

Hypogonadism in a male refers to a decrease in either or both of the two major functions of the testes: sperm production and testosterone production.

This can happen for a number of reasons.

In primary hypogonadism, the testicles do not respond to hormone stimulation. This can be due to a congenital disorder such as Klinefelters syndrome, or acquired as a result of radiation treatment, chemotherapy, mumps, tumors or trauma to the testes.

In secondary hypogonadism, a disease state interferes with either the hypothalamus or pituitary gland, the main glands that release hormones to stimulate the testes to produce testosterone.

Situations that can cause secondary hypogonadism include:

Andropause is sometimes used to describe decreased testosterone due to the normal aging process. Testosterone levels in males increase until the age of 17 years. Then, starting at approximately 40 years of age, testosterone levels begin to decline at 1.2-2 percent per year.

Risk factors for hypogonadism include type 2 diabetes, obesity, renal failure, HIV, hypertension, chronic obstructive pulmonary disease (COPD) and taking glucocorticoid (steroids), opioid or antipsychotic medication therapy.

Testosterone replacement therapy (TRT) is the recommended treatment for male hypogonadism.

It is normally given as a topical gel, transdermal patch, or by injection. Oral forms of testosterone are not used due to the high risk of side effects, such as upset stomach.

TRT can eliminate many, if not all, of the signs and symptoms of male hypogonadism.

Benefits include:

However, there are a few risks associated with it.

It may lead to worsening of benign prostatic hyperplasia (BPH), acceleration of pre-existing prostate cancer, and worsening of both sleep apnea and congestive heart failure. TRT should not be started without first attending to these conditions.

All males who are using TRT require ongoing medical evaluation to determine adequate response to treatment. This will include regular blood tests and periodic digital rectal exams.

TRT is contraindicated in men with erythrocytosis, a condition involving a high volume percentage of red blood cells in the blood.

The response to TRT is individualized, and testosterone levels are not an indicator of who will respond to TRT and who will not. It is also worth noting that while it can relieve symptoms of hypogonadism, TRT does not restore fertility.

Hypogonadism can also affect females. In women with hypogonadism, the ovaries produce low levels of female sex hormones. This affects the functioning of the ovaries and the reproductive system.

Symptoms include delayed puberty and a lack of menstruation or irregular menstruation. Breasts may not develop fully and height may be affected. This may be due to a genetic problem, an autoimmune condition, or a range of environmental factors.

After puberty, a wide range of factors can lead to hypogonadism, including tumors, eating disorders, genetic problems, and surgery, such as a hysterectomy.

Symptoms will include hot flashes, mood changes, changes in energy levels, and discontinued menstruation.

Some lifestyle changes can help boost testosterone levels.

These include:

The measures can help maintain normal testosterone levels.

If an individual is at risk of or may have hypogonadism, a doctor will take a thorough medical history taken and carry out a physical examination, including blood tests.

Two key blood tests must be carried out to confirm the presence of hypogonadism:

The normal range of these blood tests has some variability, but a reading of between 300 and 1,000 nanograms per deciliter (ng/dL) is considered normal. Levels will be below the normal range in a person with hypogonadism.

For accuracy, the blood test should be drawn between the hours of 7.00 and 11.00 in the morning on at least two occasions. Additional testing may be necessary to confirm a diagnosis of hypogonadism.

Awareness of male hypogonadism is growing, but many adult men with the condition remain undiagnosed and untreated. This may negatively influence both their quality of life in men and their life span.

Any male who thinks he may have low testosterone levels should seek medical advice, as treatment can reverse most of the symptoms and risks of male hypogonadism.

However, before starting treatment with TRT, all men should discuss the risks and benefits with their health care provider.

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Male hypogonadism: Symptoms, causes, and treatment - Medical News Today

Hypogonadism is a common condition in the male population, with a higher prevalence in older men, obese men, and men with type 2 diabetes. It is estimated that approximately 35% of men older than 45 years of age and 30-50% of men with obesity or type 2 diabetes have hypogonadism.

Testosterone is an important sex hormone in men. It is secreted by the testes and is responsible for the typical male characteristics, such as facial, pubic, and body hair as well as muscle. This hormone also helps maintain sex drive, sperm production, and bone health. The brain and pituitary gland (a small gland at the base of the brain) control the production of testosterone by the testes.

Be open with your doctor about your medical history, all prescription and nonprescription drugs you are now taking, sexual problems, and any major changes in your life. Your doctor will take a thorough history of your symptoms and then complete a physical exam, including your body hair, breast tissue, and the size and consistency of the testes and scrotum.

Your doctor will also use blood tests to see if your total testosterone level is low. The normal range depends on the lab that conducts the test. To get a diagnosis of hypogonadism, you need at least two early morning (710 AM) blood tests that reveal low testosterone in addition to signs and symptoms typical of low testosterone. The cause of hypogonadism can be investigated further by your doctor. This might include additional blood tests, and sometimes imaging such as a pituitary MRI.

Male hypogonadism is a combination of low testosterone levels and the presence of any of these symptoms:

Over time, low testosterone may cause a man to lose body hair, muscle bulk, cause weak bones (osteoporosis), low red blood cells and smaller testes. Signs and symptoms (what you see and feel) vary from person to person.

There are many causes of hypogonadism. They may involve a problem with the testes or with the signal from the brain that controls testosterone secretion. Low testosterone can result from:

Improvement of testosterone levels can improve sexual concerns, bone health, muscle and anemia (low red cells in the blood). Hypogonadism can be treated with the use of doctor-prescribed testosterone replacement therapy. This treatment is safe and can be effective for men who are diagnosed with consistently abnormal low testosterone production and symptoms that are associated with this type of androgen (hormone) deficiency.

Although testosterone replacement therapy is the primary treatment option, some conditions that cause hypogonadism, such as obesity, can be reversible without testosterone therapy. These should be addressed before testosterone therapy is contemplated. If testosterone therapy is needed, goals of treatment are to improve symptoms associated with testosterone deficiency and maintain sex characteristics.

There are many different types of testosterone therapy. Method of treatment depends on the cause of low testosterone, the patients preferences, cost, tolerance, and concern about fertility. You should discuss the different options with your physician "your partner in care" to find out which therapy is right for you.

Injections: Self or doctor administered in a muscle every 12 weeks; administered at a clinic every 10 weeks for longer-acting. Side effects: uncomfortable, fluctuating symptoms.

Gels/Solutions: Applied to upper arm, shoulder, inner thigh, armpit. Side effects: may transfer to others via skin contact must wait to absorb completely into skin.

Patches: Adhere to skin every day to back, abdomen, upper arm, thigh; rotate locations to lessen skin reaction. Side effects: skin redness and rashes.

Buccal Tablets: Sticky pill applied to gums twice a day, absorbs quickly into bloodstream through gums. Side effects: gum irritation.

Pellets: Implanted under skin surgically every 36 months for consistent and long-term dosages. Side effects: pellet coming out through skin, site infection/ bleeding (rare), dose decreasing over time and hypogonadism symptoms possibly returning towards the end of dose period.

Nasal Gel: Applied by pump into each nostril 3x a day. Side effects: nasal irritation or congestion.

Sometimes a medication called clomiphene citrate is used to treat hypogonadism, but this is not FDA approved for this indication. A thorough discussion is needed with your doctor.

You should discuss with your physician how to monitor for prostate cancer and other risks to your prostate. Men with known or suspected prostate or breast cancer should not receive testosterone therapy. You should also talk to your doctor about the risks of testosterone therapy if you have, or are at risk for, heart disease or stroke. In addition, if you are planning fertility, you should not use testosterone therapy.

You should not receive testosterone therapy if you have:

Possible risks of testosterone treatment include:

If you are treated with testosterone, your doctor will need to see you regularly, along with blood tests.Testosterone therapy is only recommended for hypogonadism patients. Boosting testosterone is NOT approved by the US Food and Drug Administration (FDA) to help improve your strength, athletic performance, physical appearance, or to treat or prevent problems associated with aging. Using testosterone for these purposes may be harmful to your health.

There is no firm scientific evidence that long-term testosterone replacement is associated with either prostate cancer or cardiovascular events. The FDA requires that you are made aware that the possibility of cardiovascular events may exist during treatment. Prostate cells are stimulated by testosterone, so be extra vigilant about cancer screenings. African American men over age 45 especially those with family history of cancer are already at risk for prostate cancer.

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Hypogonadism in Men | Endocrine Society

Background

Clinical hyposmia and anosmia are commonly seen, most frequently with either post-inflammatory, age-related, or idiopathic causes being most frequent. Actual anatomical abnormalities of the olfactory groove or olfactory bulb are far less common. A recent case report showing a possible link between congenital olfactory bulb agenesis and Wolff-Parkinson-White syndrome suggested that there may be a relationship between cardiac arrhythmia and olfactory bulb development. While Kallmann syndrome (KS) is the classic syndrome involving olfactory bulb agenesis and hypogonadotropic hypogonadism, this case report and a prior report noting isolated hypogonadotropic hypogonadism and the Wolff-Parkinson-White syndrome suggest there may be more rare associations between cardiac arrhythmia and olfactory groove abnormalities.

A retrospective study was conducted to attempt to elucidate whether there may be a link between cardiac arrhythmias and olfactory anatomical abnormalities. The olfactory bulb volume (OBV) and olfactory sulcus depth (OSD) of 44 patients with cardiac arrhythmias were compared to 43 healthy control patients. Additionally, 11 patients with acute COVID-19 were also compared in those groups. Patients were seen between September and December 2020. Available MRI images were utilized.

The average right and left olfactory bulb volume was 29.4218.17 mm3 and 25.6715.29 mm3 for patients with cardiac arrhythmia, 40.7930.65 mm3 and 38.9521.87mm3 for healthy controls, and 21.3015.23 mm3 and 17.759.63 mm3 for COVID-19 patients. The average right and left olfactory sulcus depth was 7.681.31 mm and 7.471.56 mm for patients with cardiac arrhythmia, 10.671.53 mm and 10.621.67 mm for controls, and 7.910.99 mm and 8.020.88 mm for COVID-19 patients. The right and left olfactory bulb volume difference versus controls was significant for cardiac arrhythmia patients (p=0.028 and p=0.0038) and for COVID-19 patients (p=0.047 and p=0.0029), and the right and left olfactory sulcus depth difference versus controls was significant for cardiac arrhythmia patients (p<0.0001 and p<0.0001) and for COVID-19 patients (p<0.0001 and p<0.0001). Both COVID-19 and cardiac arrhythmia patients were, on average, significantly older than controls. On multivariate analysis, cardiac arrhythmia or COVID-19 diagnosis did not significantly correlate with smaller olfactory bulb volume, but older age, cardiac arrhythmia diagnosis, and COVID-19 diagnosis did significantly correlate with smaller olfactory sulcus depth. On multivariate analysis, older age was significantly correlated with cardiac arrhythmia diagnosis and COVID-19 diagnosis.

Olfactory bulb volume and olfactory sulcus depth in both cardiac arrhythmia and COVID-19 patients appeared significantly smaller than in controls. Cardiac arrhythmia and COVID-19 patients were significantly older than controls. Age, as well as genetic predisposition, may contribute to a difference in the radiographic olfactory anatomical findings in patients with cardiac arrhythmias and COVID-19.

A recent case report [1] noted an adult patient with previously undiagnosed congenital anosmia as well as the radiographic absence of the olfactory groove/bulbs as well as Wolff-Parkinson-White syndrome. Further investigation revealed a prior case report [2] involving a patient with isolated hypogonadotropic hypogonadism, pronounced hypodontia, and the Wolff-Parkinson-White syndrome. The classic Kallmann syndrome (KS) involves hypogonadotropic hypogonadism and olfactory bulb aplasia. The presence of one of the two classic signs of Kallmann syndrome in the aforementioned case reports but not both, while both involved Wolff-Parkinson-White syndrome, prompted an investigation into whether there may be an association between cardiac arrhythmia in general and olfactory nerve abnormalities [3-7]. The gonadotropinreleasing hormone1 (GnRH) system is involved in the development of both the reproductive and olfactory systems, which may contribute to the concomitant reproductive and olfactory dysfunction seen in Kallmann syndrome patients [4,5]. Human cardiac tissue and cardiac-associated immune cells have been shown to contain GnRH receptors, and studies in cephalopods have suggested that GnRH may have receptor targets in the cardiovascular system, which may explain the possible link between cardiac arrhythmias and olfactory nerve abnormalities. Additionally, a recent study [8] on MRI and CT findings in patients with COVID-19-related anosmia noted that radiographic olfactory changes included olfactory cleft opacification, decreased olfactory bulb volumes (OBVs), and olfactory bulb signal abnormalities such as increased signal intensity, hyperintense foci, and microhemorrhages. Olfactory bulb volume and olfactory sulcus depth (OSD) have been shown to be altered in myriad conditions, from septo-optic dysplasia to depression, post-infectious anosmia/hyposmia, and many others [9-17]. This retrospective study aimed to determine whether patients with cardiac arrhythmias and patients with acute COVID-19 had decreased olfactory bulb volume and olfactory sulcus depth relative to healthy controls.

The patient data were collected through a retrospective review of the records of patients who presented to a university hospital between September 2020 and December 2020, underwent head/brain MRI, and fit the study inclusion and exclusion criteria. Between September and December 2020, the head/brain or maxillofacial MRI of 44 patients with cardiac arrhythmias, 43 healthy control patients, and 11 patients with acute COVID-19 were analyzed. Patients aged 18 years or older were included in the three groups. Cardiac arrhythmia patients were analyzed if they had a current diagnosis of any cardiac arrhythmia and had an available head/brain or maxillofacial MRI completed between September and December 2020. COVID-19 patients were analyzed if they had a current diagnosis of acute COVID-19 and had an available head/brain or maxillofacial MRI completed between September and December 2020. Healthy control patients were analyzed if they had an available head/brain or maxillofacial MRI completed between September and December 2020 and did not carry a current diagnosis of any cardiac arrhythmia, COVID-19, disorders of smell/taste, anosmia, hyposmia, or head trauma. Patient medications were analyzed to exclude patients taking medications that could cause anosmia/hyposmia such as intranasal zinc medications, topical decongestant intranasal sprays, and oral medications such as phenothiazines or nifedipine. Figure 1 shows a coronal MRI image illustrating the olfactory bulb and the olfactory sulcus. OBVs were calculated using volumetric analysis of the olfactory bulb on T2 MRI sequences as previously described [12] using the 3D Slicer software ver. 4.10.2 (http://www.slicer.org/). The 3D slicer software is a free, open-source software package for the analysis of medical imaging developed by Harvard University and facilitated volumetric analysis of the olfactory bulb data. The olfactory bulbs were segmented by tracing their outlines manually, and the software ran a quantification process that rendered the volume of the olfactory bulb. OSD was measured as described previously [8] on coronal T2 images by measuring the depth to the deepest point of the olfactory sulcus along a line tangent to the inferior borders of the gyrus rectus. In addition to patient diagnosis and olfactory bulb volume and sulcus depth, data on patient age and gender were compared. Patient data were de-identified and retrospective, and this study was approved by the SUNY-Upstate Institutional Review Board (1427574-1).

Patient data were compiled in Microsoft Excel (Microsoft Corporation, Redmond, Washington, USA) and the data were analyzed using XLSTAT (Addinsoft, Paris, France). Continuous variables were analyzed using the Students t-test and one-way analysis of variance (ANOVA) for comparison between groups. The Pearson Correlation/Association test was also utilized to determine the correlation between the observed data variables. Multivariate analysis was conducted via logistical regression using XLSTAT, utilizing a Newton-Raphson algorithm. The level of statistical significance was set at p < 0.05.

Table 1 shows the patient characteristics for each group. Of the 44 cardiac arrhythmia patients, 38 had atrial fibrillation only, one had atrial fibrillation and supraventricular tachycardia, three had atrial flutter, one had sick sinus syndrome, and one had prolonged Q-T syndrome. Table 2 shows the olfactory bulb volume and olfactory sulcus depth, patient age, and patient sex data and univariate analysis data for the three patient groups. The average right and left olfactory bulb volume was 29.4218.17 mm3 and 25.6715.29 mm3 for patients with cardiac arrhythmia, 40.7930.65 mm3 and 38.9521.87mm3 for healthy controls, and 21.3015.23 mm3 and 17.759.63 mm3 for COVID-19 patients. The average right and left olfactory sulcus depth was 7.681.31 mm and 7.471.56 mm for patients with cardiac arrhythmia, 10.671.53 mm and 10.621.67 mm for healthy controls, and 7.910.99 mm and 8.020.88 mm for COVID-19 patients. The right and left olfactory bulb volume difference versus controls was significant for cardiac arrhythmia patients (p=0.028 and p=0.0038) and for COVID-19 patients (p=0.047 and p=0.0029), and the right and left olfactory sulcus depth difference versus controls was significant for cardiac arrhythmia patients (p<0.0001 and p<0.0001) and for COVID-19 patients (p<0.0001 and p<0.0001). Multivariate analysis via XLSTAT utilizing logistical regression of the data using an iterative algorithm using the Newton-Raphson algorithm was performed. The multivariate analysis data are shown in Table 3. On multivariate analysis, age (p=0.001) and cardiac arrhythmia diagnosis (p=0.0001) or COVID-19 diagnosis (p=0.0001) remained significant predictors of smaller olfactory sulcus depth but not of smaller olfactory bulb volume. Patient sex was not a significant predictor of olfactory sulcus depth or olfactory bulb volume on multivariate analysis. The average age for the cardiac arrhythmia group was 76.1113.13 years (p<0.0001 vs control group), 51.8617.66 years for the control group, and 69.2717.64 years for the COVID-19 group (p=0.0005 vs. control group). Of the 44 cardiac arrhythmia patients, 28 were male and 16 were female. Of the 43 control patients, 21 were male and 22 were female. Of the 11 COVID-19 patients, six were male and five were female.

The volume of the olfactory bulbs and the depth of the olfactory sulcus are readily obtained from MRI imaging and can be used as a neuroanatomical comparative tool to assess the structure of the olfactory system in patients [18,19]. Olfactory bulb volumes and olfactory sulcus depth values [8,20] vary by patient population, MRI protocol, and measurement/calculation method but are typically on the order of 30-90 mm3 for olfactory bulb volumes and 5-10 mm for olfactory sulcus depth, similar to the average values noted in the patient population in this study. Isolated olfactory nerve agenesis is rare, as in a case report in a 12-year-old girl by Carswell et al. [21], noting a patient with congenital complete absence of the olfactory nerves. Coimbra et al. [3] also reported a similarly rare case of isolated olfactory bulb agenesis. The human olfactory apparatus develops during the fetal stage, and the developing fetus can detect odors as early as 28 weeks, and the developing olfactory bulbs can be seen on MRI at this point. Olfactory axons project from the nasal epithelium prior to the formation of the olfactory bulbs and lack a peripheral ganglion, but the synaptic structures of the future olfactory bulb have this functionality. The olfactory bulb begins to laminate at 14 weeks, but complete myelination occurs postnatally. The olfactory system does not contain direct thalamic projections, but the olfactory bulb and anterior olfactory nucleus essentially serve as thalamic surrogates. Olfactory abnormalities can be seen in children with brain malformations, endocrine disorders, chromosome anomalies, and craniofacial abnormalities [4-6]. Kallmann syndrome is a classically described syndrome presenting with congenital olfactory bulb agenesis. Kallmann syndrome is a subtype of the broader group of isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) syndromes [7]. KSconsists of hypogonadotropic hypogonadism with anosmia and a congenital absence of the olfactory bulbs. There are also less severe and somewhat more common pathologies seen in IGD, including hypothalamic amenorrhea (HA), constitutional delay of puberty (CDP), and adult-onset hypogonadotropic hypogonadism (AHH). The association between hypothalamic hypogonadism and olfactory bulb agenesis in Kallmann syndrome is thought to be related to the association between the GnRH neurons and the olfactory placode. IGD can also be related to non-reproductive features such as midline facial defects, renal agenesis, limb abnormalities, hearing loss, and eye movement and balance disorders.

Acquired olfactory dysfunction can be commonly seen in post-upper respiratory infection (URI) anosmia or hyposmia [10]. Studies have shown that olfactory bulb volume and olfactory sulcus depth decreased in patients with olfactory loss after URI compared to normal controls. Studies have also shown that there may be significant gray matter volume loss in the right orbitofrontal cortex (OFC) in patients with post-infectious olfactory disfunction and that there may be a significant negative correlation between the volume of gray matter in the right OFC as well as olfactory bulb volume with the duration of olfactory loss in these post-infectious olfactory loss patients versus normal controls. Kandemirli et al. [8] examined olfactory function and CT and MRI findings in patients with persistent COVID-19 olfactory dysfunction. They evaluated olfactory function with the Sniffin' Sticks test and collected quantitative measurements of olfactory bulb volumes, olfactory sulcus depths, and olfactory radiographic characteristics. They noted frequent olfactory cleft opacification (~73.9% of cases), subnormal olfactory bulb volumes in ~43.5% of cases, and shallow olfactory sulci in ~60.9% of cases. They also noted frequent abnormalities in olfactory bulb shape, olfactory bulb signal intensity, and frequent microhemorrhages and abnormalities in the clumping of or scarcity of olfactory filia. Studies have also shown that olfactory bulb volume can be decreased in patients with depression, after transsphenoidal pituitary surgery, in patients with Parkinsons disease, and that olfactory bulb volume can be decreased in women and with increasing age [11-17].

In this study, olfactory bulb volume and olfactory sulcus depth in patients with cardiac arrhythmia, acute COVID-19, and healthy controls were measured. Patients with cardiac arrhythmia and COVID-19 had significantly smaller right and left olfactory bulb volumes and olfactory sulcus depths than controls on univariate analysis and were significantly older than controls. On multivariate analysis, olfactory bulb volume did not correlate significantly with cardiac arrhythmia diagnosis or COVID-19 diagnosis. On multivariate analysis, smaller right and left olfactory sulcus depth did significantly correlate with cardiac arrhythmia and COVID-19 diagnosis. On multivariate analysis, older age was also significantly correlated with cardiac arrhythmia and COVID-19 diagnosis. This may indicate that there may be a correlation between the propensity to develop cardiac arrhythmia and the propensity for olfactory dysfunction or atrophy of the olfactory bulb and/or olfactory sulcus over time. This study's limitations include its retrospective nature, which introduces the possibility of recall and selection bias. Given the retrospective nature of this study, there was some heterogeneity in the MRI studies/sequences available for patients in this study. A prospective study in which all patients had a uniform fine-cut MRI protocol standardized for the study protocol and specifically targeted at the olfactory anatomy would be helpful. Additionally, the relatively low patient numbers are a limitationand may limit power in the statistical analysis. Patient medication lists were screened to exclude patients on intranasal or oral medications that may affect olfaction, but the use of medications not reported by patients and not present in the medical record or use of other patient medications that might unknowingly affect olfaction is another possible limitation. The mild diversity in the arrhythmia types in the cardiac arrhythmia group (although the vast majority were atrial fibrillation patients) and the mild heterogeneity in the diagnoses of the control group may also limit the statistical analysis. Future prospective studies with larger patient numbers and a greater diversity of other cardiac arrhythmia types with distinct statistical analyses for each arrhythmia type (e.g., a large number of purely Wolff-Parkinson-White patients) would be of use. The significantly older age of the cardiac arrhythmia and COVID-19 patients may also act as a confounder, and indeed, on multivariate analysis, older age did significantly correlate with smaller olfactory sulcus depth, as did cardiac arrhythmia diagnosis and COVID-19 diagnosis. This may indicate that cardiac arrhythmia, COVID-19 diagnosis or susceptibility, and older age may all correlate significantly with small olfactory sulcus depth, and that older age is also independently correlated with a propensity for cardiac arrhythmia. Additionally, the collection and availability of a formal, standardized olfactory function measurement in all patients, such as Sniffin sticks or the Pittsburgh Smell Identification test, would also allow useful correlation between functional/clinical olfactory data (quantitative olfactory measurements) and radiographic olfactory bulb volume and olfactory sulcus depth data.

This retrospective radiographic study demonstrated smaller olfactory bulb volumes and olfactory sulcus depths on MRI in patients with a history of cardiac arrhythmia and patients with COVID-19 compared to healthy control patients. Cardiac arrhythmia and COVID-19 patients were significantly older than controls. Multivariate analysis demonstrated that cardiac arrhythmia diagnosis and COVID-19 diagnosis, as well as older age, were all significantly associated with smaller olfactory sulcus depth but not with smaller olfactory bulb volume. Future prospective studies with standardized MRI protocols and larger groups of patients with cardiac arrhythmias and larger numbers of healthy controls may help elucidate whether there is a correlation between a predisposition to cardiac arrhythmia and radiographic abnormalities in the olfactory bulb/olfactory sulcus.

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Olfactory Radioanatomical Findings in Patients With Cardiac Arrhythmias, COVID-19, and Healthy Controls - Cureus

The GlobalHormone Replacement Therapy Market Size was estimated at USD 16227.83 million in 2021 and is projected to reach USD 18029.01 million by 2028, exhibiting a CAGR of 1.51% during the forecast period.

Hormone Replacement Therapy Market Insights 2022 By Types (Estrogen Hormone, Growth Hormone, Thyroid Hormone, Testosterone Hormone), Applications (Menopause, Hypothyroidism, Growth Hormone Deficiency, Male Hypogonadism, Other Diseases), Regions and Forecast to 2028. The global Hormone Replacement Therapy market size is projected to reach multi million by 2028, in comparison to 2022, with unexpected CAGR during the forecast period, the Hormone Replacement Therapy Market Report Contains strong>120 pages Including Full TOC, Tables and Figures, and Chart with In-depth Analysis Pre and Post COVID-19 Market Outbreak Impact Analysis and Situation by Region.

We have been tracking the direct impact of COVID-19 on this market, as well as the indirect impact from other industries. This report analyzes the impact of the pandemic on the Hormone Replacement Therapy market from a Global and Regional perspective. The report outlines the market size, market characteristics, and market growth for Hormone Replacement Therapy industry, categorized by type, application, and consumer sector. In addition, it provides a comprehensive analysis of aspects involved in market development before and after the Covid-19 pandemic. Report also conducted a PESTEL analysis in the industry to study key influencers and barriers to entry.

Final Report will add the analysis of the impact of COVID-19 on this industry.

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It also provides accurate information and cutting-edge analysis that is necessary to formulate an ideal business plan, and to define the right path for rapid growth for all involved industry players. With this information, stakeholders will be more capable of developing new strategies, which focus on market opportunities that will benefit them, making their business endeavours profitable in the process.

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This Hormone Replacement Therapy Market report offers detailed analysis supported by reliable statistics on sale and revenue by players for the period 2017-2022. The report also includes company description, major business, Hormone Replacement Therapy product introduction, recent developments and Hormone Replacement Therapy sales by region, type, application and by sales channel.

The major players covered in the Hormone Replacement Therapy market report are:

Eli Lilly

Short Summery About Hormone Replacement Therapy Market :

The Global Hormone Replacement Therapy market is anticipated to rise at a considerable rate during the forecast period, between 2022 and 2028. In 2021, the market is growing at a steady rate and with the rising adoption of strategies by key players, the market is expected to rise over the projected horizon.

Report Overview

Hormone replacement therapy refers to the treatment of the patients with hormone deficiency due to conditions such as dwarfism or women nearing menopause, which requires replacement of hormones in the body whose levels have become low.

Market competition is intense. Eli Lilly, Pfizer, AbbVie, Novo Nordisk, etc. are the leaders of the industry, and they hold key technologies and patents, with high-end customers. Top 5 players combined 45.13% market share in all.

The Global Hormone Replacement Therapy Market Size was estimated at USD 16227.83 million in 2021 and is projected to reach USD 18029.01 million by 2028, exhibiting a CAGR of 1.51% during the forecast period.

Bosson Researchs latest report provides a deep insight into the global Hormone Replacement Therapy market covering all its essential aspects. This ranges from a macro overview of the market to micro details of the market size, competitive landscape, development trend, niche market, key market drivers and challenges, SWOT analysis, Porters five forces analysis, value chain analysis, etc.

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Report further studies the market development status and future Hormone Replacement Therapy Market trend across the world. Also, it splits Hormone Replacement Therapy market Segmentation by Type and by Applications to fully and deeply research and reveal market profile and prospects.

On the basis of product typethis report displays the production, revenue, price, market share and growth rate of each type, primarily split into:

On the basis of the end users/applicationsthis report focuses on the status and outlook for major applications/end users, consumption (sales), market share and growth rate for each application, including:

Hormone Replacement Therapy Market Regional Analysis:

Geographically, this report is segmented into several key regions, with sales, revenue, market share and growth Rate of Hormone Replacement Therapy in these regions, from 2015 to 2027, covering

Some of the key questions answered in this report:

Our research analysts will help you to get customized details for your report, which can be modified in terms of a specific region, application or any statistical details. In addition, we are always willing to comply with the study, which triangulated with your own data to make the market research more comprehensive in your perspective.

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1 Hormone Replacement Therapy Market Overview

1.1 Product Overview and Scope of Hormone Replacement Therapy1.2 Hormone Replacement Therapy Segment by Type1.2.1 Global Hormone Replacement Therapy Market Size Growth Rate Analysis by Type 2022 VS 20281.3 Hormone Replacement Therapy Segment by Application1.3.1 Global Hormone Replacement Therapy Consumption Comparison by Application: 2022 VS 20281.4 Global Market Growth Prospects1.4.1 Global Hormone Replacement Therapy Revenue Estimates and Forecasts (2017-2028)1.4.2 Global Hormone Replacement Therapy Production Capacity Estimates and Forecasts (2017-2028)1.4.3 Global Hormone Replacement Therapy Production Estimates and Forecasts (2017-2028)1.5 Global Market Size by Region1.5.1 Global Hormone Replacement Therapy Market Size Estimates and Forecasts by Region: 2017 VS 2021 VS 20281.5.2 North America Hormone Replacement Therapy Estimates and Forecasts (2017-2028)1.5.3 Europe Hormone Replacement Therapy Estimates and Forecasts (2017-2028)1.5.4 China Hormone Replacement Therapy Estimates and Forecasts (2017-2028)1.5.5 Japan Hormone Replacement Therapy Estimates and Forecasts (2017-2028)

2 Market Competition by Manufacturers2.1 Global Hormone Replacement Therapy Production Capacity Market Share by Manufacturers (2017-2022)2.2 Global Hormone Replacement Therapy Revenue Market Share by Manufacturers (2017-2022)2.3 Hormone Replacement Therapy Market Share by Company Type (Tier 1, Tier 2 and Tier 3)2.4 Global Hormone Replacement Therapy Average Price by Manufacturers (2017-2022)2.5 Manufacturers Hormone Replacement Therapy Production Sites, Area Served, Product Types2.6 Hormone Replacement Therapy Market Competitive Situation and Trends2.6.1 Hormone Replacement Therapy Market Concentration Rate2.6.2 Global 5 and 10 Largest Hormone Replacement Therapy Players Market Share by Revenue2.6.3 Mergers and Acquisitions, Expansion

3 Production Capacity by Region3.1 Global Production Capacity of Hormone Replacement Therapy Market Share by Region (2017-2022)3.2 Global Hormone Replacement Therapy Revenue Market Share by Region (2017-2022)3.3 Global Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.4 North America Hormone Replacement Therapy Production3.4.1 North America Hormone Replacement Therapy Production Growth Rate (2017-2022)3.4.2 North America Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.5 Europe Hormone Replacement Therapy Production3.5.1 Europe Hormone Replacement Therapy Production Growth Rate (2017-2022)3.5.2 Europe Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.6 China Hormone Replacement Therapy Production3.6.1 China Hormone Replacement Therapy Production Growth Rate (2017-2022)3.6.2 China Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)3.7 Japan Hormone Replacement Therapy Production3.7.1 Japan Hormone Replacement Therapy Production Growth Rate (2017-2022)3.7.2 Japan Hormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)

4 Global Hormone Replacement Therapy Consumption by Region4.1 Global Hormone Replacement Therapy Consumption by Region4.1.1 Global Hormone Replacement Therapy Consumption by Region4.1.2 Global Hormone Replacement Therapy Consumption Market Share by Region4.2 North America4.2.1 North America Hormone Replacement Therapy Consumption by Country4.2.2 United States4.2.3 Canada4.3 Europe4.3.1 Europe Hormone Replacement Therapy Consumption by Country4.3.2 Germany4.3.3 France4.3.4 U.K.4.3.5 Italy4.3.6 Russia4.4 Asia Pacific4.4.1 Asia Pacific Hormone Replacement Therapy Consumption by Region4.4.2 China4.4.3 Japan4.4.4 South Korea4.4.5 China Taiwan4.4.6 Southeast Asia4.4.7 India4.4.8 Australia4.5 Latin America4.5.1 Latin America Hormone Replacement Therapy Consumption by Country4.5.2 Mexico4.5.3 Brazil

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5 Segment by Type5.1 Global Hormone Replacement Therapy Production Market Share by Type (2017-2022)5.2 Global Hormone Replacement Therapy Revenue Market Share by Type (2017-2022)5.3 Global Hormone Replacement Therapy Price by Type (2017-2022)6 Segment by Application6.1 Global Hormone Replacement Therapy Production Market Share by Application (2017-2022)6.2 Global Hormone Replacement Therapy Revenue Market Share by Application (2017-2022)6.3 Global Hormone Replacement Therapy Price by Application (2017-2022)

7 Key Companies Profiled7.1 Company7.1.1 Hormone Replacement Therapy Corporation Information7.1.2 Hormone Replacement Therapy Product Portfolio7.1. CHormone Replacement Therapy Production Capacity, Revenue, Price and Gross Margin (2017-2022)7.1.4 Companys Main Business and Markets Served7.1.5 Companys Recent Developments/Updates

8 Hormone Replacement Therapy Manufacturing Cost Analysis8.1 Hormone Replacement Therapy Key Raw Materials Analysis8.1.1 Key Raw Materials8.1.2 Key Suppliers of Raw Materials8.2 Proportion of Manufacturing Cost Structure8.3 Manufacturing Process Analysis of Hormone Replacement Therapy8.4 Hormone Replacement Therapy Industrial Chain Analysis

9 Marketing Channel, Distributors and Customers9.1 Marketing Channel9.2 Hormone Replacement Therapy Distributors List9.3 Hormone Replacement Therapy Customers

10 Market Dynamics10.1 Hormone Replacement Therapy Industry Trends10.2 Hormone Replacement Therapy Market Drivers10.3 Hormone Replacement Therapy Market Challenges10.4 Hormone Replacement Therapy Market Restraints

11 Production and Supply Forecast11.1 Global Forecasted Production of Hormone Replacement Therapy by Region (2022-2028)11.2 North America Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)11.3 Europe Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)11.4 China Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)11.5 Japan Hormone Replacement Therapy Production, Revenue Forecast (2022-2028)

12 Consumption and Demand Forecast12.1 Global Forecasted Demand Analysis of Hormone Replacement Therapy12.2 North America Forecasted Consumption of Hormone Replacement Therapy by Country12.3 Europe Market Forecasted Consumption of Hormone Replacement Therapy by Country12.4 Asia Pacific Market Forecasted Consumption of Hormone Replacement Therapy by Region12.5 Latin America Forecasted Consumption of Hormone Replacement Therapy by Country

13 Forecast by Type and by Application (2022-2028)13.1 Global Production, Revenue and Price Forecast by Type (2022-2028)13.1.1 Global Forecasted Production of Hormone Replacement Therapy by Type (2022-2028)13.1.2 Global Forecasted Revenue of Hormone Replacement Therapy by Type (2022-2028)13.1.3 Global Forecasted Price of Hormone Replacement Therapy by Type (2022-2028)13.2 Global Forecasted Consumption of Hormone Replacement Therapy by Application (2022-2028)13.2.1 Global Forecasted Production of Hormone Replacement Therapy by Application (2022-2028)13.2.2 Global Forecasted Revenue of Hormone Replacement Therapy by Application (2022-2028)13.2.3 Global Forecasted Price of Hormone Replacement Therapy by Application (2022-2028)

14 Research Finding and Conclusion

15 Methodology and Data Source15.1 Methodology/Research Approach15.1.1 Research Programs/Design15.1.2 Market Size Estimation15.1.3 Market Breakdown and Data Triangulation15.2 Data Source15.2.1 Secondary Sources15.2.2 Primary Sources15.3 Author List15.4 Disclaimer

Continued.

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