Notes

Sox9 Is Crucial regarding Mesenchymal Stem Tissue to further improve Cutaneous Injure Healing.
Overall, an increasing number of chronic conditions was dose-dependently associated with lower levels of social participation [e.g., ≥4 vs. 0 conditions ß=-0.26 (95%CI=-0.39, -0.13)]. The association was more pronounced among males than females.

Older people with multimorbidity had lower levels of social participation in LMICs. Future longitudinal studies are warranted to further investigate temporal associations, and whether addressing social participation can lead to better health outcomes among older people with multimorbidity in LMICs.
Older people with multimorbidity had lower levels of social participation in LMICs. Future longitudinal studies are warranted to further investigate temporal associations, and whether addressing social participation can lead to better health outcomes among older people with multimorbidity in LMICs.Early-life nutrition interventions can have lifelong cardiometabolic benefits. Most evidence on this topic is derived from observational studies. We evaluated the association of randomized controlled nutritional trials in early life and long-term cardiometabolic outcomes. Through literature search of PubMed, CABI Global Health, Embase, and Cochrane, with manual reference check and weekly alert from PubMed, we identified 8312 records, and included 53 records from 40 cohorts in 21 countries. The total number of participants was 33,551. Interventions were initiated as early as conception, and the longest until 7 y (except 1 study from infancy to 20 y). The cohorts were followed up for between 3 and 73 y. We identified 7 types of interventions (protein-energy supplements, long-chain PUFAs, single micronutrient, multiple micronutrients, infant and young child feeding, dietary counseling, and other) and 4 categories of cardiometabolic outcomes (biomarkers, cardiovascular, body size and composition, and subclinical/mote long-term cardiometabolic health.Sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) intakes have been reported to be associated with mortality; however, conclusions have been inconsistent. This review synthesized the evidence on the associations of SSB and ASB intakes with mortality from all causes, cardiovascular disease (CVD), and cancer among all populations (including general, diseased, or occupational populations, etc.). PubMed, EMBASE, Web of Science, Cochrane Library, ProQuest, ClinicalTrials.gov, and the International Clinical Trials Registry Platform were searched up to March 2020. Fifteen studies including 17 cohorts were included in meta-analyses. Each serving (12 fluid ounces or 355 mL) increase in daily SSB consumption was associated with higher risks of all-cause (HR 1.08; 95% CI 1.04, 1.12; 11 cohorts with 965,851 participants) and CVD (HR 1.08; 95% CI 1.04, 1.12; 13 cohorts with 898,005 participants) mortality. The associations of ASB intakes with all-cause and CVD mortality were J-shaped, and HRs (95% CI) across different doses (0, 1, 1.5, 2, and 2.5 servings/d) were 1.00, 1.01 (0.99, 1.03), 1.04 (1.02, 1.07), 1.08 (1.05, 1.11), and 1.13 (1.09, 1.18) for all-cause mortality and 1.00, 1.01 (0.96, 1.07), 1.07 (1.01, 1.13), 1.15 (1.08, 1.23), and 1.25 (1.14, 1.37) for CVD mortality. No significant association was found for cancer mortality. Myrcludex B nmr According to the NutriGrade scoring system, the quality of evidence on the associations of SSB intakes with all-cause and CVD mortality was high, and the quality of evidence on other associations was low to moderate. In summary, higher SSB and ASB intakes were associated with higher risks of all-cause mortality and CVD mortality. Given the limited evidence, future studies should further investigate the association between ASB intakes and cause-specific mortality.Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features and poor prognosis. We performed a subset analysis of 282 patients with AITL enrolled between 2006 and 2018 in the international prospective T-cell Project (NCT01142674). The primary and secondary endpoints were 5-year overall survival (OS) and progression-free survival (PFS), respectively. We analyzed the prognostic impact of clinical covariates and progression of disease within 24 months (POD24) and developed a novel prognostic score. The median age was 64 years, and 90% of patients had advanced stage disease. Eighty-one percent received anthracycline-based regimens and 13% underwent consolidative autologous stem cell transplant (ASCT) in first complete remission (CR1). Five-year OS and PFS estimates were 44% and 32%, respectively, with improved outcomes for patients who underwent ASCT in CR1. In multivariate analysis, age ³60 years, ECOG performance status >2, elevated C-reactive protein, and elevated β2 microglobulin were associated with inferior outcomes. A novel prognostic score (AITL score) combining these factors defined low, intermediate, and high-risk subgroups with 5-year OS estimates of 63%, 54%, and 21%, respectively, with greater discriminant power than established prognostic indices. Finally, POD24 was a powerful prognostic factor with 5-year OS of 63% for patients without POD24 compared to only 6% for patients with POD24 (p less then 0.0001). These data will require validation in a prospective cohort of homogeneously treated patients. Optimal treatment of AITL continues to be an unmet need and novel therapeutic approaches are required.In this retrospective study, (1->3)-β-D-glucan (B-glucan) was an unreliable marker for AIDS-related Pneumocystis jirovecii pneumonia (PCP) because a high percentage of participants with progressive disseminated histoplasmosis and respiratory symptoms had a positive B-glucan result. Where histoplasmosis is common attributing B-glucan positivity to PCP without further testing risks misdiagnosis.Liver diseases present a significant public health burden worldwide. Although the mechanisms of liver diseases are complex, it is generally accepted that inflammation is commonly involved in the pathogenesis. Ongoing inflammatory responses exacerbate liver injury, or even result in fibrosis and cirrhosis. Here we report that roscovitine, a cyclin-dependent kinase (CDK) inhibitor, exerts beneficial effects on acute and chronic liver inflammation as well as fibrosis. Animal models of lipopolysaccharide (LPS)/d-galactosamine- and acute or chronic CCl4-induced liver injury showed that roscovitine administration markedly attenuated liver injury, inflammation and histological damage in LPS/d-galactosamine- and CCl4-induced acute liver injury models, which is consistent with the results in vitro. RNA sequencing (RNA-seq) analysis showed that roscovitine treatment repressed the transcription of a broad set of pro-inflammatory genes involved in many aspects of inflammation, including cytokine production and immune cell proliferation and migration, and inhibited the TGF-β signaling pathway and the biological process of tissue remodeling. For further validation, the beneficial effect of roscovitine against inflammation was evaluated in chronic CCl4-challenged mice. The anti-inflammation effect of roscovitine was observed in this model, accompanied with reduced liver fibrosis. The anti-fibrotic mechanism involved inhibition of profibrotic genes and blocking of hepatic stellate cell (HSC) activation. Our data show that roscovitine administration protects against liver diseases through inhibition of macrophage inflammatory actions and HSC activation at the onset of liver injury.The COVID-19 pandemic has stimulated massive investment in biomedical research with the aims of understanding the disease and developing effective vaccine and therapeutic interventions. What role should animal research play in this scientific endeavor? Both the urgency to evaluate candidate interventions for human use and growing societal concern about ethical treatment of (nonhuman) animals put into question the justifiability of animal research as a precursor to clinical trials. Yet forgoing animal research in the rush to undertake human testing might expose human research participants to unacceptable risks. In this article, we apply a recently developed framework of principles for animal research ethics in exploring ethical questions raised by a SARS-CoV-2 infection challenge experiment involving rhesus macaques, which evaluated the protective efficacy of the mRNA-1273 vaccine that was recently approved for emergency use. Our aim is to illuminate the ethical issues while introducing, and illustrating the use of, the framework.Acalabrutinib has demonstrated significant efficacy and safety in relapsed chronic lymphocytic leukemia (CLL). Efficacy and safety of acalabrutinib monotherapy were evaluated in a treatment-naive CLL cohort of a single-arm phase 1/2 trial (ACE-CL-001). Adults were eligible for enrollment if chemotherapy was declined or deemed inappropriate due to comorbidities (N = 99). Patients had a median age of 64 years and 47% had Rai stage III/IV disease. Acalabrutinib was administered orally 200 mg once daily, or 100 mg twice daily until progression or intolerance. A total of 99 patients were treated; 57 (62%) had unmutated immunoglobulin heavy-chain variable gene, and 12 (18%) had TP53 aberrations. After median follow-up of 53 months, 85 patients remain on treatment; 14 discontinued treatment, mostly because of adverse events (AEs) (n = 6) or disease progression (n = 3). Overall response rate was 97% (90% partial response; 7% complete response), with similar outcomes among all prognostic subgroups. link2 Because of improved trough BTK occupancy with twice-daily dosing, all patients were transitioned to 100 mg twice daily. link3 Median duration of response (DOR) was not reached; 48-month DOR rate was 97% (95% confidence interval, 90-99). Serious AEs were reported in 38 patients (38%). AEs required discontinuation in 6 patients (6%) because of second primary cancers (n = 4) and infection (n = 2). Grade ≥3 events of special interest included infection (15%), hypertension (11%), bleeding events (3%), and atrial fibrillation (2%). Durable efficacy and long-term safety of acalabrutinib in this trial support its use in clinical management of symptomatic, untreated patients with CLL.The abundance of genetic abnormalities and phenotypic heterogeneities in acute myeloid leukemia (AML) poses significant challenges to the development of improved treatments. Here, we demonstrated that a key growth arrest-specific gene 6/AXL axis is highly activated in cells from patients with AML, particularly in stem/progenitor cells. We developed a potent selective AXL inhibitor that has favorable pharmaceutical properties and efficacy against preclinical patient-derived xenotransplantation (PDX) models of AML. Importantly, inhibition of AXL sensitized AML stem/progenitor cells to venetoclax treatment, with strong synergistic effects in vitro and in PDX models. Mechanistically, single-cell RNA-sequencing and functional validation studies uncovered that AXL inhibition, alone or in combination with venetoclax, potentially targets intrinsic metabolic vulnerabilities of AML stem/progenitor cells and shows a distinct transcriptomic profile and inhibits mitochondrial oxidative phosphorylation. Inhibition of AXL or BCL-2 also differentially targets key signaling proteins to synergize in leukemic cell killing.
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