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Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

In this trial, the safety and efficacy of a recombinant chimpanzee adenovirus 3 vector priming vaccination and a recombinant modified vaccinia Ankara boost was assessed in adults who were at risk for HCV infection because of injection drug use. The vaccine did not cause serious adverse events and did elicit HCV-specific T-cell responses, but it did not prevent chronic HCV infection.

Background Increasing choice among HIV pre-exposure prophylaxis (PrEP) products bears potential to increase uptake, persistence, and coverage amongst those at risk of HIV acquisition. Few studies have evaluated PrEP persistence during real-world delivery of multiple PrEP products from community-based sites to adolescents and young people. Methods The PrEPared to Choose (PtC) study delivers PrEP choice across oral, injectable, and vaginal ring options to adolescents and young people (15–29 years) and their potential male partners in Cape Town, South Africa. This phase 3B clinical trial utilizes a type 2 hybrid implementation design with co-primary clinical and implementation aims that include an analysis of PrEP persistence (defined as sustained use of PrEP product as intended with < 7 vs. < 28 day gap in dosing as scheduled) over the short term (7 months) and long term (18 months), and the identification of implementation strategies that best support PrEP adoption and persistence. PtC is delivered from a mobile clinic and a public health primary care clinic, staffed by trained nurses, HIV counsellors, and peer-navigators. PrEP selection is guided by a co-created PrEP choice counselling intervention, with allowance for product switching at subsequent visits, but no reimbursement for PrEP uptake or return. Discussion PrEPared to Choose will provide an early report of real-world PrEP choice delivery, including all three currently available and approved modalities. The protocol is designed to simulate a real-world environment that provides insight into likely PrEP persistence patterns and practical challenges to PrEP choice implementation in a high HIV burden setting (South Africa) and within high HIV incidence populations (adolescents and young people). The results will be used to inform PrEP choice delivery in South Africa and build a framework into which future, emerging PrEP modalities can be incorporated. Trial approvals and registration This is a phase 3B clinical trial registered with the South African Health Products Regulatory Authority (20230904). Ethical approval was granted by the Human Research Ethics Committee (Faculty of Health Sciences, University of Cape Town, 567/2023). It is registered with the South African National Clinical Trial Registry (DOH-27-012024-5189, 26 January 2024) and ClinicalTrials.gov (NCT06807736, retrospectively registered on 4 February 2025).

Background Adolescents and young people (AYP) are at increased risk of HIV acquisition and onward transmission in South Africa. The benefits of oral pre-exposure prophylaxis (PrEP) are well established, however, epidemic impact depends on access, effective use and scale-up. Methods FastPrEP is an implementation science project that aims to scale up oral and novel PrEP modalities through differentiated service delivery to improve uptake and optimal use of PrEP in key populations. Designed to leverage some of the attributes that make fast-food popular such as efficiency, access, variety (choice) and flexibility, FastPrEP aims to further “demedicalise” the buy-in and access to HIV prevention methods. Attracting young people regardless of HIV serostatus, FastPrEP will deliver PrEP as part of integrated sexual and reproductive health (SRH) packages tailored for key youth populations using mobile clinics ( n  = 4) and local government clinics ( n  = 12) as “hubs” for PrEP initiation. These and other community-based outlets such as youth clubs, courier delivery, schools and other youth frequented venues will serve as “spokes” for PrEP maintenance. FastPrEP aims to scale up PrEP in a dense, HIV-burdened, peri-urban community of approximately one million people in Cape Town. We will adopt the RE-AIM framework to evaluate the FastPrEP intervention among diverse AYP aged 15–29 years (targeting approximately 25 000 AYP) and their sexual partners of any age. We will use a phased approach to build the program and evaluate PrEP uptake and persistence in AYP over time. Discussion The overall objective is to evaluate whether community-wide, differentiated delivery of PrEP with regard to user choice leads to greater PrEP uptake among sexually active youths who would benefit most from comprehensive HIV protection. Secondary objectives include evaluating the differences in demographic, socio-behavioural, and risk behaviours between PrEP users and non-PrEP users to determine the effectiveness of demand creation strategies and evaluate the utility of different PrEP outlets. FastPrEP will evaluate the scale-up of community-delivered, differentiated PrEP to AYP and their sexual partners, aiming to improve understanding of the differentiated delivery of PrEP services and their impact on PrEP persistence in key populations.

Even though management scholars have offered several views on the process of corporate sustainability, these efforts have focused mainly on the technical aspects of sustainability while omitting the fundamental role played by individual moral competences. Therefore, previous work offers an incomplete and somewhat reductionist view of corporate sustainability. In this article, we develop a holistic framework of corporate sustainability in which both the moral and technical aspects of sustainability are considered. We do so by integrating the ethical, normative perspective of the Catholic social teaching (CST) with the competitive view of the natural resource-based view. This framework highlights the importance of CST principles and ideas in developing executive moral competences such as moral sensitivity and awareness, and moral cognition and motivation. Moral competences, in turn, influence the organizational selection of environmental strategies, giving leaders the intrinsic motivation to promote both a longer-term stance on corporate sustainability efforts and a relentless search for greener business models. Such strategies move the firm closer towards achieving environmental sustainability. Hence, by bridging the individual, normative-ethical with the organizational, implementational levels of corporate sustainability, our framework provides a more realistic, coherent, and complete perspective on the complex process of achieving corporate sustainability.

Patch-clamp recording has enabled single-cell electrical, morphological and genetic studies at unparalleled resolution. Yet it remains a laborious and low-throughput technique, making it largely impractical for large-scale measurements such as cell type and connectivity characterization of neurons in the brain. Specifically, the technique is critically limited by the ubiquitous practice of manually replacing patch-clamp pipettes after each recording. To circumvent this limitation, we developed a simple, fast, and automated method for cleaning glass pipette electrodes that enables their reuse within one minute. By immersing pipette tips into Alconox, a commercially-available detergent, followed by rinsing, we were able to reuse pipettes 10 times with no degradation in signal fidelity, in experimental preparations ranging from human embryonic kidney cells to neurons in culture, slices, and in vivo . Undetectable trace amounts of Alconox remaining in the pipette after cleaning did not affect ion channel pharmacology. We demonstrate the utility of pipette cleaning by developing the first robot to perform sequential patch-clamp recordings in cell culture and in vivo without a human operator.

Extracellular matrix remodelling of the adipose tissue has a pivotal role in the pathophysiology of obesity. Galectin-3 (Gal-3) is increased in obesity and mediates inflammation and fibrosis in the cardiovascular system. However, the effects of Gal-3 on adipose tissue remodelling associated with obesity remain unclear. Male Wistar rats were fed either a high-fat diet (33.5% fat) or a standard diet (3.5% fat) for 6 weeks. Half of the animals of each group were treated with the pharmacological inhibitor of Gal-3, modified citrus pectin (MCP; 100 mg kg −1 per day) in the drinking water. In adipose tissue, obese animals presented an increase in Gal-3 levels that were accompanied by an increase in pericellular collagen. Obese rats exhibited higher adipose tissue inflammation, as well as enhanced differentiation degree of the adipocytes. Treatment with MCP prevented all the above effects. In mature 3T3-L1 adipocytes, Gal-3 (10 −8 m ) treatment increased fibrosis, inflammatory and differentiation markers. In conclusion, Gal-3 emerges as a potential therapeutic target in adipose tissue remodelling associated with obesity and could have an important role in the development of metabolic alterations associated with obesity.

Obesity increases the risk of developing major diseases such as diabetes and cardiovascular disease. Adipose tissue, particularly adipocytes, may play a major role in the development of obesity and its comorbidities. The aim of this study was to characterise, in adipocytes from obese people, the most differentially expressed genes that might be relevant to the development of obesity. We carried out microarray gene profiling of isolated abdominal subcutaneous adipocytes from 20 non-obese (BMI 25+/-3 kg/m2) and 19 obese (BMI 55+/-8 kg/m2) non-diabetic Pima Indians using Affymetrix HG-U95 GeneChip arrays. After data analyses, we measured the transcript levels of selected genes based on their biological functions and chromosomal positions using quantitative real-time PCR. The most differentially expressed genes in adipocytes of obese individuals consisted of 433 upregulated and 244 downregulated genes. Of these, 410 genes could be classified into 20 functional Gene Ontology categories. The analyses indicated that the inflammation/immune response category was over-represented, and that most inflammation-related genes were upregulated in adipocytes of obese subjects. Quantitative real-time PCR confirmed the transcriptional upregulation of representative inflammation-related genes (CCL2 and CCL3) encoding the chemokines monocyte chemoattractant protein-1 and macrophage inflammatory protein 1alpha. The differential expression levels of eight positional candidate genes, including inflammation-related THY1 and C1QTNF5, were also confirmed. These genes are located on chromosome 11q22-q24, a region with linkage to obesity in the Pima Indians. This study provides evidence supporting the active role of mature adipocytes in obesity-related inflammation. It also provides potential candidate genes for susceptibility to obesity.

Although several studies have identified risk factors for high blood pressure (BP), data from Afro-Caribbean populations are limited. Additionally, less is known about how putative risk factors operate in young adults and how social factors influence the risk of high BP. In this study, we estimated the relative risk for elevated BP or hypertension (EBP/HTN), defined as BP ≥ 120/80 mmHg, among young adults with putative cardiovascular disease (CVD) risk factors in Jamaica and evaluated whether relative risks differed by sex. Data from 898 young adults, 18-20 years old, were analysed. BP was measured with a mercury sphygmomanometer after participants had been seated for 5 min. Anthropometric measurements were obtained, and glucose, lipids and insulin measured from a fasting venous blood sample. Data on socioeconomic status (SES) were obtained via questionnaire. CVD risk factor status was defined using standard cut-points or the upper quintile of the distribution where the numbers meeting standard cut-points were small. Relative risks were estimated using odds ratios (OR) from logistic regression models. Prevalence of EBP/HTN was 30% among males and 13% among females (  < 0.001 for sex difference). There was evidence for sex interaction in the relationship between EBP/HTN and some of risk factors (obesity and household possessions), therefore we report sex-specific analyses. In multivariable logistic regression models, factors independently associated with EBP/HTN among men were obesity (OR 8.48, 95% CI [2.64-27.2],  < 0.001), and high glucose (OR 2.01, CI [1.20-3.37],  = 0.008), while high HOMA-IR did not achieve statistical significance (OR 2.08, CI [0.94-4.58],  = 0.069). In similar models for women, high triglycerides (OR 1.98, CI [1.03-3.81],  = 0.040) and high HOMA-IR (OR 2.07, CI [1.03-4.12],  = 0.039) were positively associated with EBP/HTN. Lower SES was also associated with higher odds for EBP/HTN (OR 4.63, CI [1.31-16.4],  = 0.017, for moderate vs. high household possessions; OR 2.61, CI [0.70-9.77],  = 0.154 for low vs. high household possessions). Alcohol consumption was associated with lower odds of EBP/HTN among females only; OR 0.41 (CI [0.18-0.90],  = 0.026) for drinking <1 time per week vs. never drinkers, and OR 0.28 (CI [0.11-0.76],  = 0.012) for drinking ≥3 times per week vs. never drinkers. Physical activity was inversely associated with EBP/HTN in both males and females. Factors associated with EBP/HTN among Jamaican young adults include obesity, high glucose, high triglycerides and high HOMA-IR, with some significant differences by sex. Among women lower SES was positively associated with EBP/HTN, while moderate alcohol consumption was associated lower odds of EBP/HTN.

The Aedes aegypti mosquito transmits both dengue (DENV) and Zika (ZIKV) viruses. Individuals in endemic areas are at risk for infection with both viruses as well as repeated DENV infection. In the presence of anti-DENV antibodies, outcomes of secondary DENV infection range from mild to life-threatening. Further, the role of cross-reactive antibodies on the course of ZIKV infection remains unclear.We assessed the ability of cross-reactive DENV monoclonal antibodies or polyclonal immunoglobulin isolated after DENV vaccination to upregulate type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) in response to both heterotypic DENV- and ZIKV- infected cells. We found a range in the ability of antibodies to increase pDC IFN production and a positive correlation between IFN production and the ability of an antibody to bind to the infected cell surface. Engagement of Fc receptors on the pDC and Fab binding of an epitope on infected cells was required to mediate increased IFN production by providing specificity to and promoting pDC sensing of DENV or ZIKV. This represents a mechanism independent of neutralization by which pre-existing cross-reactive DENV antibodies could protect a subset of individuals from severe outcomes during secondary heterotypic DENV or ZIKV infection.