Individual Responses Research Articles

Influence of Solute Carrier Family 22 Member 1 (SLC22A1) Gene Polymorphism on Metformin Pharmacokinetics and HbA1c Levels: A Systematic Review.

Solute Carrier Family 22 Member 1 (SLC22A1, also known as OCT1) protein has a vital role in the metabolism of metformin, a first-line anti-diabetes medication. Genetic polymorphism in SLC22A1 influences individual response to metformin. This review aims to compile the current knowledge about the effects of SLC22A1 genetic polymorphism on metformin pharmacokinetics and HbA1c levels. We followed the PRISMA 2020 standards to conduct a systematic review. We searched the publications for all appropriate evidence on the effects of SLC22A1 genetic polymorphism on metformin pharmacokinetics and HbA1c from January 2002 to December 2022. Initial database searches identified 7,171 relevant studies. We reviewed 155 titles and abstracts after deleting duplicates. After applying inclusion and exclusion criteria, 23 studies remained. Three studies found that rs12208357, rs34059508, and G465R had a considerable impact (p < 0.05) on metformin pharmacokinetics, resulting in increased metformin plasma (Cmax), a higher active amount of drug in the blood (AUC), and lower volume of distribution (Vd) (p<0.05). SLC22A1 polymorphisms with effects on HbA1c include rs628031 (four of seven studies), rs622342 (four of six studies), rs594709 (one study), rs2297374, and rs1867351 (one of two studies), rs34130495 (one study), and rs11212617 (one study) (p < 0.05).

Synergistic response to climate stressors in coral is associated with genotypic variation in baseline expression.

As environments are rapidly reshaped due to climate change, phenotypic plasticity plays an important role in the ability of organisms to persist and is considered an especially important acclimatization mechanism for long-lived sessile organisms such as reef-building corals. Often, this ability of a single genotype to display multiple phenotypes depending on the environment is modulated by changes in gene expression, which can vary in response to environmental changes via two mechanisms: baseline expression and expression plasticity. We used transcriptome-wide expression profiling of eleven genotypes of common-gardened Acropora cervicornis to explore genotypic variation in the expression response to thermal and acidification stress, both individually and in combination. We show that the combination of these two stressors elicits a synergistic gene expression response, and that both baseline expression and expression plasticity in response to stress show genotypic variation. Additionally, we demonstrate that frontloading of a large module of coexpressed genes is associated with greater retention of algal symbionts under combined stress. These results illustrate that variation in the gene expression response of individuals to climate change stressors can persist even when individuals have shared environmental histories, affecting their performance under future climate change scenarios.

Abstract 104: Profiling peripheral blood to predict response to targeted androgen receptor axis therapy in mice

Abstract Background: Targeting the androgen receptor (AR) signaling axis (ARAT) continues to be the mainstay treatment for advanced-stage prostate cancer. Using second-generation antiandrogens like abiraterone acetate (Abi) and apalutamide (Apa) has contributed to the survival of prostate cancer patients. However, resistance to these therapies remains a problem and most of these patients progress to castration-resistant prostate cancer (CRPC). Myeloid-derived suppressor cells (MDSCs) have been shown to drive CRPC. We previously showed that unfavorable responses to androgen deprivation therapy (ADT) or ADT plus Apa were associated with polymorphonuclear MDSCs (PMN-MDSCs) cells enriched in prostate tumors from conditional Pten/Trp53-double knockout (DKO) mice. Here, we explore the association between pre-treatment immune cell subsets blood and antitumor to ARAT therapy DKO mice. Methods: Twenty-eight-week-old DKO mice were surgically castrated and after four weeks were randomized to treatments with vehicle, Apa or Abi for an additional four weeks (n=20). Individual treatment responses were assessed and classified according to tumor burden as follows: high tumor burden (HTB), ≥20% of median; moderate tumor burden (MTB), -20% to 20% of median; or low tumor burden (LTB), ≤-20% of median. Peripheral blood was collected both before and after treatment and analyzed by multi-color flow cytometry panels for lymphoid and myeloid subsets. Blood samples from healthy wildtype and untreated DKO mice with castration-naïve prostate tumors were collected as reference samples. Subsets of PMN-MDSCs and monocytic-MDCSs (m-MDSCs) were represented as % of total abundance and 5 of parental population. revealed a signature that was correlated with treatment responses. Profiles were constructed and the data was used to train supervised learning models to predict treatment responses. Shapely additive explanations (ShAP) were used to determine feature importance. The model was tested and validated on an independent cohort of 20 DKO mice treated with ADT and ADT plus Abi. Results: Moderate prediction from baseline blood could be identified for tumor burden following ARAT using a Naïve Bayes classifier. Model evaluation, using an independent cohort, yielded favorable performance with area under the curve (AUC) mean, 0.707; HTB, 0.627; MTB, 0.750; and LTB, 0.745. The most important features for prediction were identified. Conclusion: Our study revealed that MDSC subsets present in blood were associated with treatment responses to ARAT. Citation Format: Marco A. De Velasco, Yurie Kura, Kazuko Sakai, Yoshitaka Saito, Takafumi Minami, Kazuhiro Yoshimura, Kazutoshi Fujita, Kazuto Nishio, Hirotsugu Uemura. Profiling peripheral blood to predict response to targeted androgen receptor axis therapy in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 104.

How Colonialism Contributed to the Racialized History of Indigenous People by Unethical Diagnostic Implementations of Categories and Classifications – Overlooking Exceptionalities

ABSTRACT This article looks at how colonialism has contributed to the racialized history of Indigenous people by unethical diagnostic implementations of categories and classifications, while overlooking exceptionalities when assessing Indigenous people. By understanding how settler-colonial assessments and/or diagnostic tests have been developed and utilized on Indigenous peoples, the reader can grasp the severity of any misdiagnoses, which can contribute to mislabeling due to cultural factors that have not been included and are beyond the understanding of the often non-Indigenous evaluator. Having an assessment or diagnoses, though, is a method to obtain accommodations and specialized education. Yet, if the systems that were created do not accurately measure the responses of the Indigenous individual, then an injustice will occur, not only for a possible misdiagnosis, but also for a missed opportunity to offer help if required. The need to understand the total individual beyond a mere assessment can provide insightful information, which is crucial for the examinee and examiner. It can affect the life of the whole person being assessed, if done without the Indigenous information that has been omitted.

Investigation of deep learning model for predicting immune checkpoint inhibitor treatment efficacy on contrast-enhanced computed tomography images of hepatocellular carcinoma

Although the use of immune checkpoint inhibitors (ICIs)-targeted agents for unresectable hepatocellular carcinoma (HCC) is promising, individual response variability exists. Therefore, we developed an artificial intelligence (AI)-based model to predict treatment efficacy using pre-ICIs contrast-enhanced computed tomography (CT) imaging characteristics. We evaluated the efficacy of atezolizumab and bevacizumab in 43 patients at the Nagasaki University Hospital from 2020 to 2022 using the modified Response Evaluation Criteria in Solid Tumors. A total of 197 Progressive Disease (PD), 271 Partial Response (PR), and 342 Stable Disease (SD) contrast CT images of HCC were used for training. We used ResNet-18 as the Convolutional Neural Network (CNN) model and YOLOv5, YOLOv7, YOLOv8 as the You Only Look Once (YOLO) model with precision-recall curves and class activation maps (CAMs) for diagnostic performance evaluation and model interpretation, respectively. The 3D t-distributed Stochastic Neighbor Embedding was used for image feature analysis. The YOLOv7 model demonstrated Precision 53.7%, Recall 100%, F1 score 69.8%, mAP@0.5 99.5% for PD, providing accurate and clinically versatile predictions by identifying decisive points. The ResNet-18 model had Precision 100% and Recall 100% for PD. However, the CAMs sites did not align with the tumors, suggesting the CNN model is not predicting that a given CT slice is PD, PR, or SD, but that it accurately predicts Individual Patient's CT slices. Preparing substantial training data for tumor drug effect prediction models is challenging compared to general tumor diagnosis models; hence, large-scale validation using an efficient YOLO model is warranted.

The individual response to antibiotics and diet - insights into gut microbial resilience and host metabolism.

Antibiotic use disrupts microbial composition and activity in humans, but whether this disruption in turn affects host metabolic health is unclear. Cohort studies show associations between antibiotic use and an increased risk of developing obesity and type 2 diabetes mellitus. Here, we review available clinical trials and show the disruptive effect of antibiotic use on the gut microbiome in humans, as well as its impact on bile acid metabolism and microbial metabolites such as short-chain fatty acids. Placebo-controlled human studies do not show a consistent effect of antibiotic use on body weight and insulin sensitivity at a population level, but rather an individual-specific or subgroup-specific response. This response to antibiotic use is affected by the resistance and resilience of the gut microbiome, factors that determine the extent of disruption and the speed of recovery afterwards. Nutritional strategies to improve the composition and functionality of the gut microbiome, as well as its recovery after antibiotic use (for instance, with prebiotics), require a personalized approach to increase their efficacy. Improved insights into key factors that influence the individual-specific response to antibiotics and dietary intervention may lead to better efficacy in reversing or preventing antibiotic-induced microbial dysbiosis as well as strategies for preventing cardiometabolic diseases.

Public Opinion Through Art: Exploring Chinese University Students' Perspectives on COVID-19 Mass Nucleic Acid Testing.

In the context of the global COVID-19 pandemic, this study focuses on Chinese university students, employing graphic elicitation as a qualitative research method to analyze their hand-drawn paintings and related descriptions. Augmented by A/r/tography and metacognitive methods, the research aims to unveil the participants' collective memory, as well as the perspectives and responses of these students to policies related to the pandemic. By specifically examining this particular demographic, the study incorporates Fairclough's ethical theory, applying deontological ethics, consequentialist ethics, and virtue ethics to establish a comprehensive framework for evaluating adjustments to pandemic response policies. This research not only enhances our understanding of how these university students perceive and adapt to COVID-19 policies but also provides valuable insights for decision-makers. The particular methodology, combining graphic elicitation and metacognitive research, contributes to policy assessment and ethical analysis, offering a nuanced perspective on the interplay between individual perceptions, policy responses, and ethical considerations amid the complexities of a public health crisis.

Gradient Hydrogels Spatially Trapped Optical Cell Profiling for Quantitative Blood Cellular Osmotic Analysis.

The quantitative exploration of cellular osmotic responses and a thorough analysis of osmotic pressure-responsive cellular behaviors are poised to offer novel clinical insights into current research. This underscores a paradigm shift in the long-standing approach of colorimetric measurements triggered by red cell lysis. In this study, we engineered a purpose-driven optofluidic platform to facilitate the goal. Specifically, creating photocurable hydrogel traps surmounts a persistent challenge─optical signal interference from fluid disturbances. This achievement ensures a stable spatial phase of cells and the acquisition of optical signals for accurate osmotic response analysis at the single-cell level. Leveraging a multigradient microfluidic system, we constructed gradient osmotic hydrogel traps and developed an imaging recognition algorithm, empowering comprehensive analysis of cellular behaviors. Notably, this system has successfully and precisely analyzed individual and clustered cellular responses within the osmotic dimension. Prospective clinical testing has further substantiated its feasibility and performance in that it demonstrates an accuracy of 92% in discriminating complete hemolysis values (n = 25) and 100% in identifying initial hemolysis values (n = 25). Foreseeably, this strategy should promise to advance osmotic pressure-related cellular response analysis, benefiting further investigation and diagnosis of related blood diseases, blood quality, drug development, etc.

Bird Community Traits in Recently Burned and Unburned Parts of the Northeastern Pantanal, Brazil: A Preliminary Approach

Although fire is a natural phenomenon in the dynamics of some biomes around the world, it can threaten the biodiversity of certain ecosystems. Climate change and the expansion of anthropogenic activities have drastically increased the occurrence of large-scale burnings worldwide. The 2020 fire events in the Pantanal marked a historically unprecedented record, burning an area of approximately 40,000 km2. However, how fires affect the local wildlife has yet to be evaluated. The aim of this study was to investigate the recovery of the avifauna in the Pantanal of Mato Grosso by comparing data selected from a previous study conducted between 2014 and 2016 with data collected in burned areas nine to twelve months after the fire. We compared diversity and community composition, investigated the influence of species trait foraging guild, foraging strata, and body mass on their response to fire, and complemented it with species’ individual responses. Bird richness and Shannon diversity were lower in burned areas, and the composition significantly varied between burned and unburned areas. The species’ response toward burned and unburned areas was significantly mediated by their traits, with smaller, piscivorous, omnivorous, ground and water, and midstory to canopy species being the most sensitive toward the environmental changes caused by the fire. Thirty-three species showed a negative response toward burned areas, but 46 species showed the opposite response, and 24 species were similarly abundant in unburned and burned areas. The present study is the first evaluation of the response of birds to the extreme fire events in the Pantanal and provides valuable insight into the recovery and resilience of local avifauna.

Hide ‘n seek: individual behavioural responses of cattle excreting different amounts of nematode eggs—potential threshold for pasture contamination assessment

The aim of this study was to investigate how the activity of cattle under natural grazing conditions is related to their individual parasite contribution (IPC). Potentially, the individuals contributing the most to the contamination of the pasture with gastrointestinal nematodes (GIN) could then be identified and selectively treated based on sensor data thresholds. A total of 58 steers of the dairy breeds Swedish Red (SR, n = 19) and Swedish Holstein (SH, n = 39) were used for sensor-based data collection that lasted for a total of 10 weeks from 4 May to 13 July 2022. All steers were inoculated with a priming dose of nematode larvae and weighed in conjunction with the pasture release. The animals were then divided into four experimental groups and treated with ivermectin (IVM PO, Boehringer Ingelheim, 0.5 mg/kg BW) at different intervals to obtain an exposure contrast (Group A was left untreated, Group B/IVM PO-4w was treated after 4 weeks, Group C/IVM PO-8w was treated after 8 weeks, and Group D/IVM PO-4&amp;amp;8w was treated after 4 weeks and then after 8 weeks). The steers were weighed on four further occasions, during which faecal samples were also taken for parasite testing. Activity data were collected using leg-mounted IceQube sensors and body weight data and faecal samples were collected bi-weekly. The new threshold metric (IPC) was proposed for individuals with different faecal egg count (FEC) levels [NO (no contribution) &amp;lt;20 EPG, LO (low contribution) = 20–150 EPG, ME (medium contribution) = 150–250 EPG, and HI (high contribution) ≥250 EPG] The effects of IPC on activity patterns were analysed stepwise using a Generalised Estimating Equations model implemented in Python programming language. Results showed significant effects of different IPC values on motion index and number of steps taken (adjusted p-value of 0.008, 0.018, 0.041, and 0.001 for individuals with NO, LO, ME, and HI IPC values, respectively). There were some breed effects on the average number of steps and minutes spent lying. The results also provide alternative threshold methods aimed at finding more sustainable ways of using anthelmintics and integrating individual data into future parasite control strategies.

Omicron breakthrough infections after triple-dose inactivated COVID-19 vaccination: A comprehensive analysis of antibody and T-cell responses.

This study longitudinally evaluated the immune response in individuals over a year after receiving three doses of an inactivated SARS-CoV-2 vaccine, focusing on reactions to Omicron breakthrough infections. From 63 blood samples of 37 subjects, results showed that the third booster enhanced the antibody response against Alpha, Beta, and Delta VOCs but was less effective against Omicron. Although antibody titres decreased post-vaccination, SARS-CoV-2-specific T-cell responses, both CD4+ and CD8+ , remained stable. Omicron breakthrough infections significantly improved neutralization against various VOCs, including Omicron. However, the boost in antibodies against WT, Alpha, Beta, and Delta variants was more pronounced. Regarding T cells, breakthrough infection predominantly boosted the CD8+ T-cell response, and the intensity of the spike protein-specific T-cell response was roughly comparable between WT and Omicron BA.5.

Topical anaesthesia for invasive procedures in dermatology and cosmetology

Currently, in dermatology and cosmetology, the range of cosmetic procedures and minor invasive interventions, which use local anesthetics, is expanding. They are used alone or as part of an integrated anesthetic approach. Procedures such as mesotherapy, biorevitalization, contour plastic surgery, removal of skin tumors, and laser procedures require anesthesia in the form of local topical anesthesia. Local anesthetics have long been known and well-studied; they have many advantages, significantly increasing patient comfort during invasive procedures, but they also have some disadvantages, including the risk of toxicity. The purpose of using a local anesthetic is to increase the effectiveness of the procedure, convenience and comfort for the patient, minimize negative emotions associated with pain, and the ability to achieve local anesthesia without anatomical distortion of the tissue (i.e., without the use of infiltration anesthesia). Often, the severity of the pain experienced depends on the individual response of the patient. The characteristics of pain are subjective and can vary depending on the “pain threshold”, type of temperament, and previous negative experience. For some patients, sometimes minimal pain becomes a serious obstacle to performing a particular procedure. Some invasive, painful procedures that are performed on pediatric patients require a particularly careful approach to the choice of anesthesia drug and method of administration. In this article, we analyzed the mechanisms of pain pathogenesis, methods of local anesthesia, focused on the role of local anesthetics in cosmetology and dermatology, examined the features of using a cream for local and external use containing a combination of lidocaine 2.5% and prilocaine 2.5%, its therapeutic effectiveness, clinical recommendations for use in various procedures in dermatology and cosmetology. When choosing a drug for local anesthesia, safety is important for the doctor, when used correctly, a low level of side effects, timely pain relief, effectiveness, ease of use and accessibility.

Associations between immune-inflammatory markers, age, and periodontal status: a cross-sectional study.

Since periodontal disease is associated with many systemic diseases, it is important to evaluate its effects on host responses in elderly individuals. To this end, this study investigated salivary interleukin (IL)-17, IL-18, toll-like receptor (TLR) 2, TLR4, and tumor necrosis factor-alpha (TNF-α) levels in patient groups with different periodontal health statuses and immunologically evaluated the relationship between age and periodontal health status. A total of 60 individuals aged 18-40years (young individuals) and 60 individuals aged 65years or older (elderly individuals) were included in this study. According to periodontal disease status, the patients were divided into periodontally healthy, gingivitis, and periodontitis subgroups. Clinical periodontal parameters, including probing depth (PD), clinical attachment level (CAL), plaque index (PI), and gingival index (GI), were recorded. Saliva samples were collected and analyzed using ELISA to determine the levels of IL-17, IL-18, TLR2, TLR4, and TNF-α. Higher clinical periodontal parameter (PD, CAL, PI, and GI) and inflammatory marker (IL-17, IL-18, TNF-α, TLR2, and TLR4) levels were found in patients with periodontitis than those in periodontally healthy individuals and patients with gingivitis (P < 0.05). Salivary inflammatory marker levels were significantly higher in elderly individuals than those in young individuals in all subgroups (P < 0.05). A positive correlation was found between inflammatory marker levels and clinical periodontal parameters, but there was no correlation between TLR2 and PI or GI. This study suggests a significant increase in host response to periodontal disease as the disease progresses, with the levels of cytokines and TLR expression exhibiting an increasing trend with age. Increased IL-17, IL-18, TLR2, TLR4, and TNF-α levels in elderly individuals in all periodontal health subgroups might suggest the role of these cytokines and TLR pathway in the pathogenesis of periodontal diseases.

Advances in understanding bat infection dynamics across biological scales.

Over the past two decades, research on bat-associated microbes such as viruses, bacteria and fungi has dramatically increased. Here, we synthesize themes from a conference symposium focused on advances in the research of bats and their microbes, including physiological, immunological, ecological and epidemiological research that has improved our understanding of bat infection dynamics at multiple biological scales. We first present metrics for measuring individual bat responses to infection and challenges associated with using these metrics. We next discuss infection dynamics within bat populations of the same species, before introducing complexities that arise in multi-species communities of bats, humans and/or livestock. Finally, we outline critical gaps and opportunities for future interdisciplinary work on topics involving bats and their microbes.

Centre variation in home dialysis uptake: A survey of kidney centre practice in relation to home dialysis organisation and delivery in England.

Disparities in home dialysis uptake across England suggest inequity and unexplained variation in access. We surveyed staff at all English kidney centres to identify patterns in service organisation/delivery and explore correlations with home therapy uptake, as part of a larger study ('Inter-CEPt'), which aims to identify potentially modifiable factors to address observed variations. Between June and September 2022, staff working at English kidney centres were surveyed and individual responses combined into one centre-level response per question using predetermined data aggregation rules. Descriptive analysis described centre practices and their correlation with home dialysis uptake (proportion of new home dialysis starters) using 2019 UK Renal Registry 12-month home dialysis incidence data. In total, 180 responses were received (50/51 centres, 98.0%). Despite varied organisation of home dialysis services, most components of service delivery and practice had minimal or weak correlations with home dialysis uptake apart from offering assisted peritoneal dialysis and 'promoting flexible decision-making about dialysis modality'. Moderate to strong correlations were identified between home dialysis uptake and centres reporting supportive clinical leadership (correlation 0.32, 95% Confidence Interval (CI): 0.05-0.55), an organisational culture that values trying new initiatives (0.57, 95% CI: 0.34-0.73); support for reflective practice (0.38, 95% CI: 0.11-0.60), facilitating research engagement (0.39, 95% CI: 0.13-0.61) and promoting continuous quality improvement (0.29, 95% CI: 0.01-0.53). Uptake of home dialysis is likely to be driven by organisational culture, leadership and staff attitudes, which provide a supportive clinical environment within which specific components of service organisation and delivery can be effective.

Murals and Graffiti in Ruins: What Does the Art from the Aliko Hotel on Naxos Tell Us?

This manuscript investigates the cultural and educational dimensions of murals and graffiti in the ruins of the Aliko Hotel on Naxos Island. Moving beyond their aesthetic value, these artworks are examined as conduits for complex sociocultural and educational discourses. Employing semiotic analysis, particularly informed by Roland Barthes’ conceptual framework, the study offers a multi-layered interpretation of the significance of street art. A systematic approach guided the empirical data collection, entailing the careful selection and categorisation of 76 photographs, eventually honed down to 21 key images for detailed analysis. This set, comprising 6 murals and 15 graffiti pieces, was subjected to meticulous examination to discern both dominant themes and motifs (‘studium’) and the elements evoking personal connections (‘punktum’), thereby facilitating emotional and intellectual engagement. The methodology of the study is tailored to uncover the collective narratives encapsulated within these visual forms, as well as the individual responses they provoke. It probes how personal interpretations are influenced by the viewers’ beliefs and backgrounds, thereby expanding the semiotic analysis to encompass both shared and individual meanings. This balanced analytical approach deepens the understanding of visual expressions as dynamic interactions between the artwork and its audience. It underscores the transformative role of street art in urban environments and its contribution to public art discourse. The impending demolition of the Hotel Aliko ruins underscores the ephemeral nature of street art. The murals and graffiti, as transient custodians of cultural and social narratives, accentuate the fragile nature of this cultural heritage. This critical moment underscores the importance of documenting and preserving such art forms and the stories they encapsulate, highlighting their significant role in shaping community identity and cultural education.

Exploring the interplay of psychological and biological components of stress response and telomere length in the transition from middle age to late adulthood: A systematic review.

Ageing and chronic stress have been linked to reduced telomere length (TL) in mixed-age groups. Whether stress response components are linked to TL during the midlife-to-late adulthood transition remains unclear. Our study aimed to synthesise evidence on the relationship between psychological and biological components of stress response on TL in middle-aged and older adults. We conducted a systematic review of studies obtained from six databases (PubMed, CINAHL, EMBASE, PsycINFO, Web of Science, and Scopus) and evaluated by two independent reviewers. Original research measuring psychological and biological components of stress response and TL in human individuals were included. From an initial pool of 614 studies, 15 were included (n=9446 participants). Synthesis of evidence showed that higher psychological components of the stress response (i.e., global perceived stress or within a specific life domain and cognitive appraisal to social-evaluative stressors) were linked to shorter TL, specifically in women or under major life stressors. For the biological stress response, cortisol, dehydroepiandrosterone sulphate and IGF-1/cortisol imbalance, IL-6, MCP-1, blood pressure, and heart rate presented a significant association with TL, but this relationship depended on major life stressors and the stress context (manipulated vs. non-manipulated conditions). This comprehensive review showed that psychological and biological components of the stress response are linked to shorter TL, but mainly in women or those under a major life stressor and stress-induced conditions. The interaction between stressor attributes and psychological and biological reactions in the transition from middle to late adulthood still needs to be fully understood, and examining it is a critical step to expanding our understanding of stress's impact on ageing trajectories.

The Role of Glutathione in the Management of Cell-Mediated Immune Responses in Individuals with HIV.

Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses.

How do sports injury epidemiological outcomes vary depending on athletes' response rates to a weekly online questionnaire? An analysis of 39-week follow-up from 391 athletics (track and field) athletes.

To explore how sports injury epidemiological outcomes (i.e., prevalence, average prevalence, incidence, burden, and time to first injury) vary depending on the response rates to a weekly online self-reported questionnaire for athletes. Weekly information on athletics injuries and exposure from 391 athletics (track and field) athletes was prospectively collected over 39 weeks (control group of the PREVATHLE randomized controlled trial) using an online self-reported questionnaire. The data were used to calculate sports injury epidemiological outcomes (i.e., prevalence, average prevalence, incidence, burden, and time to first injury) for sub-groups with different minimum individual athletes' response rates (i.e., from at least 100%, at least 97%, at least 95%, … to at least 0% response rate). We then calculated the relative variation between each sub-group and the sub-group with a 100% response rate as a reference. A substantial variation was considered when the relative variation was greater than one SD or 95% CI of the respective epidemiological outcome calculated in the sub-group with a 100% response rate. Of 15 249 expected weekly questionnaires, 7209 were completed and returned, resulting in an overall response rate of 47.3%. The individual athletes' response rates ranged from 0% (n = 51) to 100% (n = 100). The prevalence, average weekly prevalence, and time to first injury only varied substantially for the sub-groups below a 5%, 10% and 18% minimum individual response rate, respectively. The incidence and injury burden showed substantial variations for all sub-groups with a response rate below 100%. Epidemiological outcomes varied depending on the minimum individual athletes' response rate, with injury prevalence, average weekly prevalence, and time to first injury varying less than injury incidence and injury burden. This highlights the need to take into account the individual response rate when calculating epidemiological outcomes, and determining the optimal study-specific cut-offs of the minimum individual response rate needed.

Shedding light on weight loss: A narrative review of medications for treating obesity.

Obesity and overweight are the major risk factors for numerous chronic diseases, including cardiovascular diseases such as heart disease and stroke, which are the leading causes of death worldwide. The prevalence of obesity has dramatically risen in both developed and developing countries, making it a significant public health concern and a global crisis. Despite lifestyle modifications being the first-line treatment, the high risk of relapse has led to a growing interest in non-invasive pharmacotherapeutic interventions to achieve and maintain weight loss and reverse the growth of the obesity epidemic. Cardiovascular diseases and cancer account for the highest mortality rates among other comorbidities associated with obesity and overweight. Excess and abnormally deposited adipose tissue secretes various inflammatory mediators, leading to cardiovascular diseases and cancers. Weight loss of 5-10% significantly reduces cardiometabolic risk. Medications currently approved in the USA for long-term management of obesity are orlistat, naltrexone, bupropion, phentermine/topiramate, and Glucagon Like Peptide-1 (GLP-1) agonists such as liraglutide and semaglutide. The benefit-to-risk of medications, comorbidities, and individual responses should guide the treatment decisions. The article provides a comprehensive overview and discussion of several weight loss medications used previously and currently, including their efficacy, mechanisms of action, and side effects.