Potentially modifiable lifestyle factors may influence cognitive health in later life and offer potential to reduce the risk of cognitive decline and dementia. The concept of cognitive reserve has ...been proposed as a mechanism to explain individual differences in rates of cognitive decline, but its potential role as a mediating pathway has seldom been explored using data from large epidemiological studies. We explored the mediating effect of cognitive reserve on the cross-sectional association between lifestyle factors and cognitive function in later life using data from a population-based cohort of healthy older people.
We analysed data from 2,315 cognitively healthy participants aged 65 y and over in the Cognitive Function and Ageing Study Wales (CFAS-Wales) cohort collected in 2011-2013. Linear regression modelling was used to investigate the overall associations between five lifestyle factors-cognitive and social activity, physical activity, diet, alcohol consumption, and smoking-and cognition, adjusting for demographic factors and chronic conditions. Mediation analysis tested for indirect effects of the lifestyle factors on cognition via cognitive reserve. After controlling for age, gender, and the presence of chronic conditions, cognitive and social activity, physical activity, healthy diet, and light-to-moderate alcohol consumption were positively associated with cognitive function, together accounting for 20% (95% CI 17%-23%) of variance in cognitive test scores. Cognitive reserve was an important mediator of this association, with indirect effects via cognitive reserve contributing 21% (95% CI 15%-27%) of the overall effect on cognition. The main limitations of the study derive from the cross-sectional nature of the data and the challenges of accurately measuring the latent construct of cognitive reserve.
Cross-sectional associations support the view that enhancing cognitive reserve may benefit cognition, and maintenance of cognitive health may be supported by a healthy and active lifestyle, in later life.
Gay and bisexual men (GBM) are a key population affected by human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection. We aimed to measure HCV treatment effectiveness and to ...determine the population impact of treatment scale-up on HCV prevalence and incidence longitudinally among GBM.
The co-EC Study (Enhancing Care and Treatment Among HCV/HIV Coinfected Individuals to Eliminate Hepatitis C Transmission) was an implementation trial providing HCV direct-acting antiviral treatment in Melbourne, Australia, during 2016-2018. Individuals with HCV/HIV coinfection were prospectively enrolled from primary and tertiary care services. HCV viremic prevalence and HCV antibody/viremic incidence were measured using a statewide, linked, surveillance system.
Among 200 participants recruited, 186 initiated treatment during the study period. Sustained virological response in primary care (98% 95% confidence interval {CI}, 93%-100%) was not different to tertiary care (98% 95% CI, 86%-100%). From 2012 to 2019, between 2434 and 3476 GBM with HIV infection attended our primary care sites annually, providing 13 801 person-years of follow-up; 50%-60% received an HCV test annually, and 10%-14% were anti-HCV positive. Among those anti-HCV positive, viremic prevalence declined 83% during the study (54% in 2016 to 9% in 2019). HCV incidence decreased 25% annually from 1.7/100 person-years in 2012 to 0.5/100 person-years in 2019 (incidence rate ratio, 0.75 95% CI, .68-.83; P < .001).
High treatment effectiveness by nonspecialists demonstrates the feasibility of treatment scale-up in this population. Substantial declines in HCV incidence and prevalence among GBM provides proof-of-concept for HCV microelimination.
NCT02786758.
The Open Source Malaria (OSM) consortium is developing compounds that kill the human malaria parasite, Plasmodium falciparum, by targeting PfATP4, an essential ion pump on the parasite surface. The ...structure of PfATP4 has not been determined. Here, we describe a public competition created to develop a predictive model for the identification of PfATP4 inhibitors, thereby reducing project costs associated with the synthesis of inactive compounds. Competition participants could see all entries as they were submitted. In the final round, featuring private sector entrants specializing in machine learning methods, the best-performing models were used to predict novel inhibitors, of which several were synthesized and evaluated against the parasite. Half possessed biological activity, with one featuring a motif that the human chemists familiar with this series would have dismissed as “ill-advised”. Since all data and participant interactions remain in the public domain, this research project “lives” and may be improved by others.
Limited research exists on rest-pause or cluster-set (CS) protocols. Acute effects of a traditional set (TS) and CS protocols of resistance exercise on serum growth hormone (GH), cortisol (C), blood ...lactate (BL), countermovement vertical jump (CMVJ) and standing long jump (SLJ) were compared. Eleven resistance-trained males (22.9 ± 2.6 year; 176.9 ± 10.6 cm; 78.5 ± 1.6 kg; 12.9 ± 3.1% BF) completed one repetition maximum tests for clean pull (CP), back squat (BS) and bench press (BP). Subjects were then randomly assigned to TS or CS protocols for sessions 2 and 3, and performed CP and BS lifts followed by two circuits of three sets of three exercises. GH, C, BL, CMVJ and SLJ were measured pre-exercise (Pre), mid-exercise following completion of CS or TS protocol (Mid), immediately (IP), 15 (15P) and 30 (30P) minutes post-exercise. Repeated measures ANOVAs examined differences in GH, C, BL, CMVJ and SLJ. No differences (p>0.05) existed between protocols for GH and C. GH levels 15P were elevated (p<0.05) above 30P (15.78 + 4.66 vs. 12.10 + 4.66 µg·L(-1)). C levels 30P were elevated (p<0.05) above Pre (716.85 + 102.56 vs. 524.79 + 75.79 nmol·L(-1)). Interaction (p <0.05) existed between protocol and time for BL; mid-BL was lower for CS than TS (7.69 ± 3.73 vs. 12.78 ± 1.90 mmol·L(-1)). Pooled data for CMVJ and SLJ were greater (p <0.05) across the CS protocol. The less metabolically taxing CS protocol resulted in better sustainability of jump measures.
It is thought that mRNA-based vaccine-induced immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wanes quickly, based mostly on short-term studies. Here, we analyzed the ...kinetics and durability of the humoral responses to SARS-CoV-2 infection and vaccination using >8,000 longitudinal samples collected over a 3-year period in New York City. Upon primary immunization, participants with pre-existing immunity mounted higher antibody responses faster and achieved higher steady-state antibody titers than naive individuals. Antibody kinetics were characterized by two phases: an initial rapid decay, followed by a stabilization phase with very slow decay. Booster vaccination equalized the differences in antibody concentration between participants with and without hybrid immunity, but the peak antibody titers decreased with each successive antigen exposure. Breakthrough infections increased antibodies to similar titers as an additional vaccine dose in naive individuals. Our study provides strong evidence that SARS-CoV-2 antibody responses are long lasting, with initial waning followed by stabilization.
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•COVID-19-vaccine-induced immunity wanes but stabilizes at an individual setpoint•Pre-existing immunity results in rapid antibody responses upon vaccination•Boosters equalize antibody titers between individuals with and without hybrid immunity•Antibody kinetics show two phases: an initial rapid decay followed by a steady state
SARS-CoV-2 mRNA-based vaccine-induced immunity is thought to wane quickly based on short-term studies. Using longitudinal data, Srivastava et al. find that participants with hybrid immunity show faster, higher antibody responses after initial vaccination, but boosters evened out differences. Modeling of antibody kinetics revealed an initial rapid decay followed by a stabilization phase, challenging the idea that vaccine immunity fades quickly.
ABSTRACT
Axion-like particles (ALPs) are predicted by several Beyond the Standard Model theories, in particular, string theory. In the presence of an external magnetic field perpendicular to the ...direction of propagation, ALPs can couple to photons. Therefore, if an X-ray source is viewed through a magnetized plasma, such as a luminous quasar in a galaxy cluster, we may expect spectral distortions that are well described by photon–ALP oscillations. We present a 571 ks combined high- and low-energy transmission grating Chandra observation of the powerful radio-quiet quasar H1821+643, hosted by a cool-core cluster at redshift 0.3. The spectrum is well described by a double power-law continuum and broad+narrow iron line emission typical of type-1 active galactic nuclei (AGNs), with remaining spectral features ${\lt}2.5{{\ \rm per\ cent}}$. Using a cell-based approach to describe the turbulent cluster magnetic field, we compare our spectrum with photon–ALP mixing curves for 500 field realizations, assuming that the thermal-to-magnetic pressure ratio β remains constant up to the virial radius. At $99.7{{\ \rm per\ cent}}$ credibility and taking β = 100, we exclude all couplings gaγ > 6.3 × 10−13 GeV−1 for most ALP masses <10−12 eV. Our results are moderately more sensitive to constraining ALPs than the best previous result from Chandra observations of the Perseus cluster, albeit with a less constrained field model. We reflect on the promising future of ALP studies with bright AGNs embedded in rich clusters, especially with the upcoming Athena mission.
Studies of early-life neurotoxicant exposure have not been designed, analyzed, or interpreted in the context of a fully developmental perspective.
The goal of this paper is to describe the key ...principles of a developmental perspective and to use examples from the literature to illustrate the relevance of these principles to early-life neurotoxicant exposures.
Four principles are discussed: 1) the effects of early-life neurotoxicant exposure depend on a child's developmental context; 2) deficits caused by early-life exposure initiate developmental cascades that can lead to pathologies that differ from those observed initially; 3) early-life neurotoxicant exposure has intra-familial and intergenerational impacts; 4) the impacts of early-life neurotoxicant exposure influence a child's ability to respond to future insults. The first principle is supported by considerable evidence, but the other three have received much less attention.
Incorporating a developmental perspective in studies of early-life neurotoxicant exposures requires prospective collection of data on a larger array of covariates than usually considered, using analytical approaches that acknowledge the transactional processes between a child and the environment and the phenomenon of developmental cascades.
Consideration of early-life neurotoxicant exposure within a developmental perspective reveals that many issues remain to be explicated if we are to achieve a deep understanding of the societal health burden associated with early-life neurotoxicant exposures.
•Studies of neurotoxicant exposures have not employed a developmental perspective.•Studies must be designed and analyzed to assess contextual effects on toxicity.•Studies must recognize the phenomenon of developmental cascades.•Studies must acknowledge the transactional nature of early child development.•Health burden will be underestimated if a developmental perspective is not employed.
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