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Frailty is associated with morbidity and premature mortality among elderly HIV-uninfected adults, but the determinants and consequences of frailty in HIV-infected populations remain unclear. We evaluated the correlates of frailty, and the impact of frailty on mortality in a cohort of aging injection drug users (IDUs). Frailty was assessed using standard criteria among HIV-infected and uninfected IDUs in 6-month intervals from 2005 to 2008. Generalized linear mixed-model analyses assessed correlates of frailty. Cox proportional hazards models estimated risk for all-cause mortality. Of 1230 participants at baseline, the median age was 48 years and 29% were HIV-infected; the frailty prevalence was 12.3%. In multivariable analysis of 3,365 frailty measures, HIV-infected IDUs had an increased likelihood of frailty (OR, 1.66; 95% CI, 1.24-2.21) compared to HIV-uninfected IDUs; the association was strongest (OR, 2.37; 95% CI, 1.62-3.48) among HIV-infected IDUs with advanced HIV disease (CD4<350 cells/mm3 and detectable HIV RNA). No significant association was seen with less advanced disease. Sociodemographic factors, comorbidity, depressive symptoms, and prescription drug abuse were also independently associated with frailty. Mortality risk was increased with frailty alone (HR 2.63, 95% CI, 1.23-5.66), HIV infection alone (HR 3.29, 95% CI, 1.85-5.88), and being both HIV-infected and frail (HR, 7.06; 95%CI 3.49-14.3). Frailty was strongly associated with advanced HIV disease, but IDUs with well-controlled HIV had a similar prevalence to HIV-uninfected IDUs. Frailty was independently associated with mortality, with a marked increase in mortality risk for IDUs with both frailty and HIV infection.

[...]despite the availability of influenza vaccines specially formulated for older adults, vaccination coverage varies widely among different countries/regions and older adults continue to suffer disproportionally high morbidity and mortality from seasonal influenza. [...]understanding of and improving influenza immunization for older adults remain a priority in translational aging research. [...]the conventional approach, i.e., measuring pre-vaccination HAI antibody titers using current season vaccine strain antigens, appeared to underestimate residual HAI antibody titers from prior season vaccination and, thus, overestimate interseason waning. [...]interseason waning and prior season post-vaccination HAI antibody titers had significant and independent impact on pre-existing humoral immunity. [...]the review article by Cadar et al.

The aim was to provide an overview of chronic low-grade inflammatory phenotype (CLIP) and evidence for its role in the pathogenesis of frailty and other chronic conditions as well as potential causative factors and interventions. We reviewed evidence from published clinical and laboratory studies and summarized the opinions of experts from published reviews. CLIP is a low-grade, systemic, unresolved, and smoldering chronic inflammatory state clearly indicated by a 2- to 4-fold increase in serum levels of inflammatory mediators, such as interleukin-6 and C-reactive protein. It involves many other cellular and molecular inflammatory mediators. CLIP typically occurs during aging, also known as “inflammaging,” and is an integral part of the spectrum of immunosenescence. Causative factors likely include persistent viral infections, particularly chronic cytomegalovirus infection, cellular senescence, failure to eliminate degraded materials and waste products, dysregulated microbiota and gut permeability, obesity, and others. Substantial evidence supports CLIP as a powerful contributing factor to frailty and many other chronic conditions and adverse health outcomes. Many of the inflammatory mediators and their regulatory mechanisms in CLIP may serve as potential targets for therapeutic intervention. However, development of new interventional strategies for CLIP and its associated chronic conditions should take the complexity of the inflammatory network into consideration. Nonpharmacologic interventions, such as caloric restriction and exercise, may have significant impact on CLIP and its causative factors, leading to substantial health benefits. Metformin and resveratrol have anti-inflammatory property and may serve as a promising therapeutic agent for treatment of CLIP and frailty. CLIP is a chronic inflammatory pathophysiologic process that plays an important role in the pathogenesis of frailty and many other chronic conditions. Improving our understanding of this phenotype may provide opportunities to identify potential targets of effective prevention and therapeutic strategies for frailty and other CLIP-associated conditions.

Frailty is a common and important geriatric syndrome characterized by age-associated declines in physiologic reserve and function across multiorgan systems, leading to increased vulnerability for adverse health outcomes. Two major frailty models have been described in the literature. The frailty phenotype defines frailty as a distinct clinical syndrome meeting three or more of five phenotypic criteria: weakness, slowness, low level of physical activity, self-reported exhaustion, and unintentional weight loss. The frailty index defines frailty as cumulative deficits identified in a comprehensive geriatric assessment. Significant progress has recently been made in understanding the pathogenesis of frailty. Chronic inflammation is likely a key pathophysiologic process that contributes to the frailty syndrome directly and indirectly through other intermediate physiologic systems, such as the musculoskeletal, endocrine, and hematologic systems. The complex multifactorial etiologies of frailty also include obesity and specific diseases. Major clinical applications include risk assessment and stratification. This can be applied to the elderly population in the community and in a variety of care settings. Frailty may also be useful for risk assessment in surgical patients and those with cardiovascular diseases, cancer, or human immunodeficiency virus infection, as well as for assessment of vaccine effectiveness in older adults. Currently, exercise and comprehensive geriatric interdisciplinary assessment and treatment are key interventions for frailty. As understanding of the biologic basis and complexity of frailty further improves, more effective and targeted interventional strategies and innovative geriatric-care models will likely be developed.

Sitagliptin is an emerging oral hypoglycemic agent that inhibits the development of a wide variety of tumors. Current researches indicate that the abnormal activation of Yes‐associated protein (YAP) promotes the proliferation and poor prognosis of multiple tumors. However, the ability of sitagliptin to regulate YAP and its effects on gastric cancer (GC) cells remain unclear. Here, we first showed that sitagliptin inhibited the proliferation of GC cells, and this inhibition was regulated by Hippo pathway. Sitagliptin phosphorylated YAP in a large tumor suppressor homolog‐dependent manner, thereby inhibiting YAP nuclear translocation, and promoted YAP cytoplasm retention. This inhibition can be blocked by adenosine 5′‐monophosphate‐activated protein kinase (AMPK). Moreover, sitagliptin could reduce the expression of tumor‐testis antigen Melanoma‐associated antigen‐A3 through YAP. In conclusion, sitagliptin may have a potential inhibitory effect on GC by AMPK/YAP/melanoma‐associated antigen‐A3 pathway. Sitagliptin inhibits the proliferation and clonality of gastric cancer cells, which was accompanied by increased levels of adenosine 5′‐monophosphate‐activated protein kinase phosphorylation and Yes‐associated protein (YAP) phosphorylation expression and decreased YAP nuclear localization. In addition, sitagliptin reduces melanoma‐associated antigen‐A3 expression via the YAP pathway, which may improve the prognosis of gastric cancer.

Tongxinluo capsule (TXLC) is a commonly used Chinese medicine for unstable angina pectoris (UA). This article aimed to clarify the safety and efficacy of TXLC as an adjunctive treatment for UA. Two reviewers searched 7 databases from inception to August 2021, and performed literature screening and information extraction independently. The meta-analysis was implemented after evaluating the methodological quality of each randomized controlled trial (RCT) by the Cochrane Risk of Bias tool. Sensitivity analyses were conducted for testing the stability of the results, and the Begg and Egger tests were performed for any potential publication bias. After eligibility assessment, 42 RCTs with a total of 5,421 participants were included. Evidence showed that TXLC reduced the rate of cardiovascular events [RR = 0.29, 95% CI (0.19, 0.45), p < 0.00001, I 2 = 0%] {including cardiovascular mortality [RR = 0.16, 95% CI (0.03, 0.88), p = 0.03, I 2 = 20%], the incidence of acute myocardial infarction [RR = 0.27, 95% CI (0.13, 0.57), p = 0.0006, I 2 = 0%] and the occurrence of revascularization [RR = 0.28, 95% CI (0.15,0.54), p = 0.0001, I 2 = 0%]}, all-cause mortality [RR = 0.25, 95% CI (0.06, 0.99), p = 0.05, I 2 = 19%], recurrence of angina [RR = 0.25, 95% CI (0.11, 0.61), p = 0.002, I 2 = 0%], the number of ST-segment depression [MD = −0.45, 95% CI (−0.69, −0.20), p = 0.0005, I 2 = 0%], the summation of ST-segment depression [MD = −0.70, 95% CI (−1.08, −0.32), p = 0.0003, I 2 = 70%] and the hypersensitive C-reactive protein level [MD = −2.86, 95% CI (−3.73, −1.99), p < 0.00001, I 2 = 86%], increased the nitric oxide level [MD = 11.67, 95% CI (8.33, 15.02), p < 0.00001, I 2 = 33%], improved the electrocardiogram change [RR = 1.23, 95% CI (1.16, 1.30), p < 0.00001, I 2 = 0%] and the clinical efficacy in UA [RR = 1.26, 95% CI (1.21, 1.32), p < 0.00001, I 2 = 24%], and relieved the symptoms of angina pectoris {including chest pain or tightness [RR = 1.13, 95% CI (0.97, 1.32), p = 0.12, I 2 = 30%], palpitations [RR = 1.47, 95% CI (1.18, 1.84), p = 0.0007, I 2 = 0%], shortness of breath [RR = 1.53, 95% CI (1.24, 1.88), p < 0.0001, I 2 = 0%], and asthenia [RR = 1.69, 95% CI (0.83, 3.43), p = 0.15, I 2 = 90%]}. The most common adverse effect was gastrointestinal symptoms which could be relieved and eliminated through dose reduction, medication time adjustment and symptomatic remedy. Collectively, TXLC was effective and considerably safe for UA. However, due to the unavoidable risk of bias, these results must be interpreted with caution and further verified by large-scale and high-quality RCTs. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/ , identifier CRD42021232771.

Background Older adults are more vulnerable to seasonal influenza than younger adults. The immune responses of older persons to the influenza vaccine are usually poorer than those of young individuals, which is hypothesized due to immunosenescence. We conducted a study to evaluate the immunogenicity and safety of a quadrivalent inactivated influenza vaccine (IIV4) in a total of 167 young (< 65 years, n  = 79) and older (≥ 65 years, n  = 88) adults from October 2021 to March 2022 in Tianjin, China. A single dose was administered to all participants. Blood samples were collected and strain-specific hemagglutination inhibition (HAI) antibody titers were measured before and 21 to 28 days after vaccination. Safety information was also collected for 28 days and 6 months after vaccination. Differences in immunogenicity and safety were compared between young and old age groups, and multivariate logistic regression was used to estimate the effect of age and other factors on HAI antibody responses. Results Overall, geometric mean titers (GMTs) against all four vaccine strains in older adults were lower than those in the young, whereas the seroconversion rates (SCRs) were similar. Multivariate logistic regression analysis showed that age, influenza vaccination history, and pre-vaccination HAI titers were independent factors affecting SCRs and seroprotection rates (SCRs). Older age had significant negative impact on SCRs against H1N1 (OR, 0.971; 95% CI: 0.944–0.999; P  = 0.042) and B/Victoria (OR, 0.964; 95% CI: 0.937–0.992; P  = 0.011). In addition, there was a significant negative correlation between chronological age (years) and post-vaccination HAI titers against H1N1 (rho = -0.2298, P  < 0.0001), B/Victoria (rho = -0.2235, P  = 0.0037), and B/Yamagata (rho = -0.3689, P  < 0.0001). All adverse events were mild (grade 1 or grade 2) that occurred within 28 days after vaccination, and no serious adverse event was observed. Conclusions IIV4 is immunogenic and well-tolerated in young and older adults living in Tianjin, China. Our findings also indicate that age is an independent factor associated with poorer humoral immune responses to IIV4.

MMAAP Foundation is a 501(c) (3) non-profit organization. 2020 MMAAP FOUNDATION FELLOWSHIP AND RESEARCH PROJECT AWARDS Applications invited MMAAP Foundation invites the submission of applications for Irma and Paul Milstein Program for Senior Health Fellowship and Research Project Awards. A letter from the applicant stating: research goals and plan for future collaboration with the US sponsor/partner institution clinical and translational impact of the project description of how this project will yield measurable results over a 2-year time period acknowledgment of the requirement to submit periodic progress reports every 6 months and an expenditure report at the end of the grant period acknowledgment of the requirement to list Irma and Paul Milstein Program for Senior Health, MMAAP Foundation support in all presentations and publications acknowledgment to keep MMAAP Foundation informed of current/future presentations and/or publications. Note: Human and/or animal use must be approved by the Institutional Review Board or equivalent and documented before funding begins.

Background Women/females report more adverse events (AE) following immunization than men/males for many vaccines, including the influenza and COVID-19 vaccines. This discrepancy is often dismissed as a reporting bias, yet the relative contributions of biological sex and gender are poorly understood. We investigated the roles of sex and gender in the rate of AE following administration of the high-dose seasonal influenza vaccine to older adults (≥ 75 years) using an AE questionnaire administered 5–8 days post-vaccination. Participant sex (male or female) was determined by self-report and a gender score questionnaire was used to assign participants to one of four gender categories (feminine, masculine, androgynous, or undifferentiated). Sex steroid hormones and inflammatory cytokines were measured in plasma samples collected prior to vaccination to generate hypotheses as to the biological mechanism underpinning the AE reported. Results A total of 423 vaccines were administered to 173 participants over four influenza seasons (2019-22) and gender data were available for 339 of these vaccinations (2020-22). At least one AE was reported following 105 vaccinations (25%), by 23 males and 82 females. The majority of AE occurred at the site of injection, were mild, and transient. The odds of experiencing an AE were 3-fold greater in females than males and decreased with age to a greater extent in females than males. The effects of gender, however, were not statistically significant, supporting a central role of biological sex in the occurrence of AE. In males, estradiol was significantly associated with IL-6 and with the probability of experiencing an AE. Both associations were absent in females, suggesting a sex-specific effect of estradiol on the occurrence of AE that supports the finding of a biological sex difference. Conclusions These data support a larger role for biological sex than for gender in the occurrence of AE following influenza vaccination in older adults and provide an initial investigation of hormonal mechanisms that may mediate this sex difference. This study highlights the complexities of measuring gender and the importance of assessing AE separately for males and females to better understand how vaccination strategies can be tailored to different subsets of the population.

Seasonal influenza infection is responsible for 3‐5 million severe illness cases and 290 000‐650 000 respiratory deaths annually worldwide. 2,3 According to the Centers for Disease Control and Prevention (CDC), influenza affects 5%‐20% of the population each year in the United States. 4 It is estimated that influenza causes 226 000 excess hospitalizations, 25 000‐69 000 deaths, and US $87 billion excess health‐care cost with over 600 000 life‐years lost annually. 5,6 Among all infectious diseases, influenza is foremost in its age‐related increase in serious complications, leading to hospitalization, catastrophic disability, and death in older adults. 7,8 Moreover, influenza frequently causes exacerbation of many chronic conditions that are common in older adults, including cardiovascular diseases, 9,10 further indirectly impacting senior health and mortality. [...]over 90% of influenza‐related mortality occurs in persons aged over 65 years. 11 In the United States, influenza and its secondary pneumonia are the fourth leading cause of death in this population. 12 Therefore, prevention and treatment of influenza in older adults have become a major public health priority. The annual vaccination is overall efficacious, with estimated risk reduction of 50%‐70% for influenza infection in young adults and less robust risk reduction in older adults. 13,14 This reduced efficacy in older adults is thought to be due to immunosenescence and common health conditions, such as frailty. 15 In recent years, a new generation of influenza vaccines, including high‐dose (HD) and adjuvanted ones, have been approved by the US Food and Drug Administration (FDA) for older adults in the United States and elsewhere, in addition to the standard dose trivalent inactivated influenza vaccine (IIV3). There is an urgent need to establish a comprehensive, nationwide influenza surveillance mechanism or network to monitor and report influenza epidemic activity with laboratory diagnosis of influenza infection and confirmation of specific virus strain for each influenza season across China.