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INTRODUCTION: Although some factors associated with asthma symptom deterioration and risk of exacerbation have been identified, these are not yet fully characterised. We conducted a clinical modelling and simulation study to understand baseline factors affecting symptom control, reliever use and exacerbation risk in patients with moderate-severe asthma during follow-up on regularly dosed inhaled corticosteroid (ICS) monotherapy, or ICS/long-acting beta2-agonist (LABA) combination therapy. METHODS: Individual patient data from randomised clinical trials (undertaken between 2001 and 2019) were used to model the time course of symptoms (n = 7593), patterns of reliever medication use (n = 3768) and time-to-first exacerbation (n = 6763), considering patient-specific and extrinsic factors, including treatment. Model validation used standard graphical and statistical criteria. Change in symptom control scores (Asthma Control Questionnaire 5 [ACQ-5]), reduction in reliever use and annualised exacerbation rate were then simulated in patient cohorts with different baseline characteristics and treatment settings. RESULTS: Being a smoker, having higher baseline ACQ-5 and body mass index affected symptom control scores, reliever use and exacerbation risk (p < 0.01). In addition, low forced expiratory volume in 1 s percent predicted, female sex, season and previous exacerbations were found to contribute to a further increase in exacerbation risk (p < 0.01), whereas long asthma history was associated with more frequent reliever use (p < 0.01). These effects were independent from the underlying maintenance therapy. In different scenarios, fluticasone furoate (FF)/vilanterol was associated with greater reductions in reliever use and exacerbation rates compared with FF or fluticasone propionate (FP) alone or budesonide/formoterol, independently from other factors (p < 0.01). CONCLUSIONS: This study provided further insight into the effects of individual baseline characteristics on treatment response and highlighted significant differences in the performance of ICS/LABA combination therapy on symptom control, reliever use and exacerbation risk. These factors should be incorporated into clinical practice as the basis for tailored management of patients with moderate-severe asthma.

In this study we quantified how individual baseline patient characteristics at the start of treatment influence the response to regular maintenance medication. Specifically, using computer modelling and simulations based on data from individual patients enrolled into clinical trials in moderate­severe asthma, we predicted how much reliever inhaler they need, how well they rate their asthma control, and how likely an asthma attack (exacerbation) is to occur within the next 12 months. Simulation scenarios were then implemented to evaluate opportunities to improve and personalise real-life management of patients in clinical practice. Considering symptom control level, reliever use and other patient-specific factors at the start of treatment, we assessed how well maintenance therapy with inhaled corticosteroids/bronchodilators contributes to symptom improvement and/or reduction in the risk of asthma attacks. These scenarios show that current smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. Moreover, this was linked to a higher risk of having an asthma attack and worse symptom control. This pattern appears to compensate in most cases for the effect of the same baseline factors on symptom control. Switching patients who are not responding well to initial treatment with the inhaled corticosteroid, fluticasone propionate, to fluticasone furoate/vilanterol resulted in a significantly greater reduction in reliever inhaler use and risk of asthma attack, compared with those switched to budesonide/formoterol. These findings highlight the importance of tailored choices for optimal management of patients with moderate­severe asthma.

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Objectives: This research summarizes the impact of the major comorbidities impacting hospitalized women with COVID-19 and their relation to death. Methods: Public data from national databases (2020-2022) for hospitalized women, including identification data, hospitalization time, comorbidities, and intensive care unit (ICU) admissions, were analyzed. Women were stratified by age (split at 50 years). Binary regression models determined the correlation between comorbidities and COVID-19 with mortality, expressed as odds ratios. Results: A total of 46,492 women were hospitalized, with 70.1% aged above 50 years. A total of 17,728 fatalities occurred, with 86.5% in the older age group. A total of 5.82% women required intensive care. The common comorbidities were pneumonia, hypertension, diabetes, obesity, and intubation. A total of 56.6% died within the 1st week; in the ICU, 65.7% died by week 2. In the logistic regression, diabetes and chronic kidney disease (CKD) were initially significant, followed by pneumonia and CKD (days 8-14), intubation and, ICU stay (beyond the 15th day). In the ICU, intubation impact worsened over time. Conclusions: Our study highlights the significant impact of comorbidities on COVID-19 mortality in women in the Valley of Mexico. Pneumonia, diabetes, CKD, and intubation were notably prevalent and correlated strongly with death in older women. Timely intubation improves survival, whereas delayed intubation increases mortality risk, particularly, in the ICU. Urgent targeted interventions are required, especially for older hospitalized women.

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OBJECTIVES: This study aims to provide a current and comprehensive analysis of the incidence of delayed intracerebral hemorrhage (dICH) in head trauma patients on oral anticoagulants and to evaluate various potential risk factors. METHODS: We conducted a systematic review and meta-analysis following PRISMA and MOOSE guidelines. PubMed and CENTRAL were searched for studies on dICH in anticoagulated head trauma patients undergoing repeat CT scans. Studies reporting dICH incidence on repeat CT within 24 hours of an initial negative scan were included. Data on demographics, anticoagulant type, risk factors, and clinical outcomes were extracted and analyzed. RESULTS: From 634 identified articles, 26 studies with 7218 patients were included. The overall incidence of dICH was 2.0%, with 43.8% of these cases requiring hospital admission or changes in clinical management. Only 0.1% required neurosurgical intervention, and 0.1% resulted in death. Meta-analysis of 20 studies revealed pooled dICH incidence per 1000 persons at risk was 27.1 for vitamin K antagonists (VKAs) and 20.5 for direct oral anticoagulants (DOACs). Significant risk factors for dICH included Glasgow Coma Scale (GCS) <15, loss of consciousness, post-traumatic amnesia, and Abbreviated Injury Scale (AIS) head ≥3. CONCLUSIONS: A low incidence of dICH requires neurosurgical intervention, however further studies are required to assess the need for other medical management in these patients. Furthermore, selective imaging for high-risk patients could improve care and resource allocation.

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Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines.

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Electrospun nanocomposite scaffolds with improved bioactive and biological properties were fabricated from a blend of polycaprolactone (PCL) and starch, and then combined with 5 wt% of calcium oxide (CaO) nanoparticles sourced from eggshells. SEM analyses showed scaffolds with fibrillar morphology and a three-dimensional structure. The hydrophilicity of scaffolds was improved with starch and CaO nanoparticles, which was evidenced by enhanced water absorption (3500 %) for 7 days. In addition, PCL/Starch/CaO scaffolds exhibited major degradation, with a mass loss of approximately 60 % compared to PCL/Starch and PCL/CaO. The PCL/Starch/CaO scaffolds decreased in crystallinity as intermolecular interactions between the nanoparticles retarded the mobility of the polymeric chains, leading to a significant increase in Young's modulus (ca. 60 %) and a decrease in tensile strength and elongation at break, compared to neat PCL. SEM-EDS, FT-IR, and XRD analyses indicated that PCL/Starch/CaO scaffolds presented a higher biomineralization capacity due to the ability to form hydroxyapatite (HA) in their surface after 28 days. The PCL/Starch/CaO scaffolds showed attractive biological performance, allowing cell adhesion and viability of M3T3-E1 preosteoblastic cells. In vivo analysis using a subdermal dorsal model in Wistar rats showed superior biocompatibility and improved resorption process compared to a pure PCL matrix. This biological analysis suggested that the PCL/Starch/CaO electrospun mats are suitable scaffolds for guiding the regeneration of bone tissue.

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PD-1 blockade has been approved for head and neck squamous cell carcinoma (HNSCC) patients. However, many HNSCC patients do not respond to this treatment, and other tumor microenvironmental factors may promote resistance to PD-1 blockade. We previously identified increased expression of the inhibitory receptor NKG2A on CD8+ T cells in HNSCC tumors compared with T cells in matching PBMC samples. Mechanisms that promote NKG2A expression and the role of NKG2A on human T cells in the tumor microenvironment, however, are uncertain. In this study, we show that tumor-conditioned media (TCM) of HNSCC cancer cell lines or ascites fluid from colorectal carcinoma patients is sufficient to induce the expression of NKG2A and other inhibitory receptors on activated CD8+ T cells isolated from PBMCs of healthy donors. Boiling or small molecular mass cutoff filtering did not eliminate the effect of TCM, suggesting that a small molecule promotes NKG2A. T cell activation in TCM decreased the basal and maximal mitochondrial respiration to metabolically restrain CD8+ T cells. Functionally, T cell activation in TCM reduced CD8+ T cell cytotoxicity as shown by lower production of cytokines, granzyme B, and perforin. Furthermore, TCM prevented CD8+ T cells from killing cancer cells in response to an anti-CD19/anti-CD3 bispecific T cell engager. Thus, a small secreted molecule from HNSCC cells can induce NKG2A expression and promote T cell dysfunction. Our findings may lead to targets for novel cancer therapies or biomarkers for NKG2A blockade response and provide a model to study T cell dysfunction and impaired metabolism.

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INTRODUCTION: Clinical remission is a relatively new concept in asthma but recent research initiatives suggest it could be an ambitious and achievable therapeutic target for patients with asthma. METHODS: In this modified Delphi study (comprising two online surveys, completed either side of a virtual scientific workshop), the opinions of a panel of respiratory physicians were evaluated to summarize perspective statements on key therapeutic outcomes and criteria for on-treatment clinical remission in patients with moderate asthma. An agreement threshold was pre-defined as agreement by ≥ 75% of participants. RESULTS: Surveys 1 and 2 were completed by 20 and 18 participants, respectively. Most participants (95%) agreed with the concept of clinical remission in moderate asthma and that this should be a desirable treatment goal (90%). Based on a composite measure of 4-6 desirable therapeutic outcomes, current understanding of clinical remission was considered as 12 months with no exacerbations, no oral corticosteroids, no daytime or night-time asthma symptoms (Asthma Control Test score ≥ 20 or Asthma Control Questionnaire score ≤ 0.75), stable lung function, and no treatment-related adverse events. No agreement was reached on the role of relievers in defining therapeutic outcomes or on the wider use of biomarkers and airway hyperresponsiveness for defining asthma remission in clinical practice. CONCLUSIONS: In line with recent consensus statements from the United States and Europe, there was a high level of agreement on the elements of clinical remission among a panel of respiratory physicians from Asia, the Middle East, and South America. Extension of the concept of clinical remission to patients with moderate asthma was considered aligned with the potential of clinical remission as a goal of therapy.

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INTRODUCTION: The relationship between immediate symptom control, reliever medication use and exacerbation risk on treatment response and factors that modify it have not been assessed in an integrated manner. Here we apply simulation scenarios to evaluate the effect of individual baseline characteristics on treatment response in patients with moderate-severe asthma on regular maintenance dosing monotherapy with fluticasone propionate (FP) or combination therapy with fluticasone propionate/salmeterol (FP/SAL) or budesonide/formoterol (BUD/FOR). METHODS: Reduction in reliever medication use (puffs/24 h), change in symptom control scores (ACQ-5), and annualised exacerbation rate over 12 months were simulated in a cohort of patients with different baseline characteristics (e.g. time since diagnosis, asthma control questionnaire (ACQ-5) symptom score, smoking status, body mass index (BMI) and sex) using drug-disease models derived from large phase III/IV clinical studies. RESULTS: Simulation scenarios show that being a smoker, having higher baseline ACQ-5 and BMI, and long asthma history is associated with increased reliever medication use (p < 0.01). This increase correlates with a higher exacerbation risk and higher ACQ-5 scores over the course of treatment, irrespective of the underlying maintenance therapy. Switching non-responders to ICS monotherapy to combination therapy after 3 months resulted in immediate reduction in reliever medication use (i.e. 1.3 vs. 1.0 puffs/24 h for FP/SAL and BUD/FOR, respectively). In addition, switching patients with ACQ-5 > 1.5 at baseline to FP/SAL resulted in 34% less exacerbations than those receiving regular dosing BUD/FOR (p < 0.01). CONCLUSIONS: We have identified baseline characteristics of patients with moderate to severe asthma that are associated with greater reliever medication use, poor symptom control and higher exacerbation risk. Moreover, the effects of different inhaled corticosteroid (ICS)/long-acting beta agonist (LABA) combinations vary significantly when considering long-term treatment performance. These factors should be considered in clinical practice as a basis for personalised management of patients with moderate-severe asthma symptoms.

In this study we looked at how different factors affect the response to asthma treatment in people with moderate to severe asthma who are taking regular medication. Specifically, we wanted to quantify how much asthma duration, differences in the degree of symptom control and lung function, as well as smoking habit, body weight, and sex influence how well someone responds to regular maintenance therapy. Using computer simulations based on models obtained from data in a large patient population with moderate­severe asthma, we explored scenarios that reflect real-life management of patients undergoing treatment with inhaled corticosteroids alone or in combination with long-acting beta agonists over a 12-month period. We looked at how much reliever inhaler they use, how well they rate their asthma control, and how often they have asthma attacks. By considering these results together, we evaluated how well the treatments work on ongoing symptoms and/or reduce the risk of future asthma attacks. Our simulations showed that smokers, people with higher asthma symptom scores, who are obese, and have a longer history of asthma tend to use their reliever inhalers more often. This was linked to a higher risk of having asthma attacks and worse symptom control. Switching those patients who do not respond well to their initial treatment with corticosteroid to combination therapy reduced how much reliever inhaler they need. Also, the effects of fluticasone propionate/salmeterol combination therapy were greater than budesonide/formoterol. In conclusion, our study found that certain patient characteristics can predict how well someone responds to asthma treatment.

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Marine heatwaves (MHWs) are episodes of anomalous warming in the ocean that can last from a few days to years. MHWs have different characteristics in terms of intensity, duration and frequency and generate thermal stress in marine ecosystems. In reef ecosystems, they are one of the main causes of the decreased presence and abundance of corals, invertebrates and fish. The deleterious capacity of thermal stress often depends on biotic factors, such as the trophic control of predators on prey. Despite the evidence of thermal stress and biotic factors affecting individual species, the combined effects of both stressors on entire reef ecosystems are much less studied. Here, using a food web modelling approach, we estimated the rate of change in species' biomass due to different MHW characteristics. Specifically, we modelled the mechanistic link between species' consumption rate and seawater temperature (thermal stressor), simulating species' biomass dynamics for different MHW characteristics under different trophic control assumptions (top-down, mixed trophic control and bottom-up). We find that total reef ecosystem biomass declined by 10% ± 5% under MHWs with severe intensity and a top-down control assumption. The bottom-up control assumption moderates the total ecosystem biomass reduction by 5% ± 5%. Irrespective of the MHW characteristics and the trophic control assumption, the most substantial biomass changes occur among top, mesopredators and corals (5% to 20% ± 10%). We show that reef ecosystems where predators exert top-down control on prey are prone to suffer species abundance declines under strong MHW events. We identify food web trophic control as a crucial driver that modulates the impacts of MHWs. Overall, our results provide a unified understanding of the interplay between abiotic stressors and biotic factors in reef ecosystems under extreme thermal events, offering insights into present baselines and future ecological states for reef ecosystems.

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In this paper, we propose a daily living situation where objects in a kitchen can be grasped and stored in specific containers using a virtual robot arm operated by different myoelectric control modes. The main goal of this study is to prove the feasibility of providing virtual environments controlled through surface electromyography that can be used for the future training of people using prosthetics or with upper limb motor impairments. We propose that simple control algorithms can be a more natural and robust way to interact with prostheses and assistive robotics in general than complex multipurpose machine learning approaches. Additionally, we discuss the advantages and disadvantages of adding intelligence to the setup to automatically assist grasping activities. The results show very good performance across all participants who share similar opinions regarding the execution of each of the proposed control modes.

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PURPOSE: To characterize current lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI +) health-related undergraduate medical education (UME) curricular content and associated changes since a 2011 study and to determine the frequency and extent of institutional instruction in 17 LGBTQI + health-related topics, strategies for increasing LGBTQI + health-related content, and faculty development opportunities. METHOD: Deans of medical education (or equivalent) at 214 allopathic or osteopathic medical schools in Canada and the United States were invited to complete a 36-question, Web-based questionnaire between June 2021 and September 2022. The main outcome measured was reported hours of LGBTQI + health-related curricular content. RESULTS: Of 214 schools, 100 (46.7%) responded, of which 85 (85.0%) fully completed the questionnaire. Compared to 5 median hours dedicated to LGBTQI + health-related in a 2011 study, the 2022 median reported time was 11 h (interquartile range [IQR], 6-16 h, p < 0.0001). Two UME institutions (2.4%; 95% CI, 0.0%-5.8%) reported 0 h during the pre-clerkship phase; 21 institutions (24.7%; CI, 15.5%-33.9%) reported 0 h during the clerkship phase; and 1 institution (1.2%; CI, 0%-3.5%) reported 0 h across the curriculum. Median US allopathic clerkship hours were significantly different from US osteopathic clerkship hours (4 h [IQR, 1-6 h] versus 0 h [IQR, 0-0 h]; p = 0.01). Suggested strategies to increase content included more curricular material focusing on LGBTQI + health and health disparities at 55 schools (64.7%; CI, 54.6%-74.9%), more faculty willing and able to teach LGBTQI + -related content at 49 schools (57.7%; CI, 47.1%-68.2%), and more evidence-based research on LGBTQI + health and health disparities at 24 schools (28.2%; CI, 18.7%-37.8%). CONCLUSION: Compared to a 2011 study, the median reported time dedicated to LGBTQI + health-related topics in 2022 increased across US and Canadian UME institutions, but the breadth, efficacy, or quality of instruction continued to vary substantially. Despite the increased hours, this still falls short of the number of hours based on recommended LGBTQI + health competencies from the Association of American Medical Colleges. While most deans of medical education reported their institutions' coverage of LGBTQI + health as 'fair,' 'good,' or 'very good,' there continues to be a call from UME leadership to increase curricular content. This requires dedicated training for faculty and students.

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OBJECTIVE: This systematic review and network meta-analysis aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) in adults aged 75 and over undergoing acute venous thromboembolism (VTE) treatment. METHODS: PubMed, Embase and the CENTRAL were searched up to 25 December 2023. The incidence of VTE recurrence and bleeding events was assessed. Employing a frequentist network meta-analysis approach, interventions not directly compared could be indirectly assessed through the 95% confidence interval (CI), enhancing the interpretability of the search results. The surface under the cumulative ranking curves (SUCRA) was utilized to generate the relative ranking probabilities for each group. RESULTS: Our study, analysing 6 randomised controlled trials with 3665 patients, compares direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in adults aged 75 and over with acute venous thromboembolism. Edoxaban reduces VTE recurrence risk compared with VKAs (risk ratio [RR] .50, 95% CI 0.27 - .95), while apixaban significantly decreases bleeding risk compared with VKAs (RR .23, 95% CI 0.08 - .69), edoxaban (RR .28, 95% CI 0.09 - .86) and rivaroxaban (RR .28, 95% CI 0.09 - .86). Despite low overall evidence quality, apixaban consistently ranks highest for both efficacy and safety. Findings underscore the nuanced efficacy-safety balance in this population, emphasizing cautious interpretation due to evidence limitations. CONCLUSION: Apixaban emerges as a favourable choice for acute VTE treatment in the elderly, displaying reduced bleeding risk compared to other treatments while maintaining comparable efficacy. Future studies should explore diverse anticoagulants efficacy and safety in older populations. Additionally, clinical prediction models tailored to geriatric cohorts are crucial for guiding treatment duration decisions.

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INTRODUCTION/BACKGROUND: Mild asthma treatment recommendations include intermittent inhaled corticosteroid (ICS)/formoterol dosing or regular ICS dosing with short-acting ß2-agonist reliever. Due to the heterogeneity of asthma, identification of traits associated with improved outcomes to specific treatments would be clinically beneficial. AIMS/OBJECTIVES: To assess the impact of patient traits on treatment outcomes of regular ICS dosing compared with intermittent ICS/formoterol dosing, a systematic literature review (SLR) and network meta-analysis (NMA) was conducted. Searches identified randomised controlled trials (RCTs) of patients with asthma aged ≥12 years, containing ≥1 regular ICS dosing or intermittent ICS/formoterol dosing treatment arm, reporting traits and outcomes of interest. RESULTS: The SLR identified 11 RCTs of mild asthma, of 14,516 patients. A total of 11 traits and 11 outcomes of interest were identified. Of these, a feasibility assessment indicated possible assessment of three traits (age, baseline lung function, smoking history) and two outcomes (exacerbation rate, change in lung function). The NMA found no significant association of any trait with any outcome with regular ICS dosing relative to intermittent ICS/formoterol dosing. Inconsistent reporting of traits and outcomes between RCTs limited analysis. CONCLUSIONS: This is the first systematic analysis of associations between patient traits and differential treatment outcomes in mild asthma. Although the traits analysed were not found to significantly interact with relative treatment response, inconsistent reporting from the RCTs prevented assessment of some of the most clinically relevant traits and outcomes, such as adherence. More consistent reporting of respiratory RCTs would provide more comparable data and aid future analyses.

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The purpose was to compare two non-laboratory based running retraining programs on lower limb and trunk kinematics in recreational runners. Seventy recreational runners (30 ± 7.3 years old, 40% female) were randomised to a barefoot running group (BAR), a group wearing a digital metronome with their basal cadence increased by 10% (CAD), and a control group (CON). BAR and CAD groups included intervals from 15 to 40 min over 10 weeks and 3 days/week. 3D sagittal kinematics of the ankle, knee, hip, pelvis, and trunk were measured before and after the retraining program, at comfortable and high speeds. A 3 × 2 mixed ANOVA revealed that BAR and CAD groups increased knee and hip flexion at footstrike, increased peak hip flexion during stance and flight phase, decreased peak hip extension during flight phase, and increased anterior pelvic tilt at both speeds after retraining. In addition, BAR increased ankle plantar flexion at footstrike and increased anterior trunk tilt. Both retraining programs demonstrated significant moderate to large effect size changes in parameters that could reduce the mechanical risks of injury associated with excessive knee stress, which is of interest to coaches, runners and those prescribing rehabilitation and injury prevention programs.

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This study investigated the effects of match location, quality of opposition (classified into: strong [1st to 4th position]; intermediate [5th to 15th position]; weak [16th to 20th position]), and match outcome on the match running performance of starters and non-starters from a top elite Brazilian soccer team. Absolute measures were calculated using total distance, high-speed (19.8-25.2 km·h-1), sprinting (≥ 25.2 km·h-1), total distance high-acceleration (> 2m·s2), and deceleration (< -2m·s2) were recorded by GPS units from a sample of young soccer players (N = 25) in a total of 17 matches. Relative measures were calculated by dividing absolute measures by the total duration of the matches. Non-starters covered greater total distance (p = 0.02), sprinting (p = 0.02), high-acceleration and deceleration (p = 0.04), sprinting distance relative per minute played (p = 0.005), and high-acceleration and deceleration relative per minute played (p < 0.001) when the team plays at home, strong opponents, and wins the matches. Starters covered greater total distance in high-speed running (p = 0.04), high-acceleration and deceleration (p = 0.03), and high-speed running relative per minute played (p = 0.04) when the team plays strong opponents and wins the matches. These findings highlight the impact of contextual factors during matches on the locomotor performance of young soccer players.

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INTRODUCTION: The relationship between brain lesions and stroke outcomes is crucial for advancing patient prognosis and developing effective therapies. Stroke is a leading cause of disability worldwide, and it is important to understand the neurological basis of its varied symptomatology. Lesion-symptom mapping (LSM) methods provide a means to identify brain areas that are strongly associated with specific symptoms. However, inner variations in LSM methods can yield different results. To address this, our study aimed to characterize the lesion-symptom mapping variability using three different LSM methods. Specifically, we sought to determine a lesion symptom core across LSM approaches enhancing the robustness of the analysis and removing potential spatial bias. MATERIAL & METHODS: A cohort consisting of 35 patients with either right- or left-sided middle cerebral artery strokes were enrolled and evaluated using the NIHSS at 24 h post-stroke. Anatomical T1w MRI scans were also obtained 24 h post-stroke. Lesion masks were segmented manually and three distinctive LSM methods were implemented: ROI correlation-based, univariate, and multivariate approaches. RESULTS: The results of the LSM analyses showed substantial spatial differences in the extension of each of the three lesion maps. However, upon overlaying all three lesion-symptom maps, a consistent lesion core emerged, corresponding to the territory associated with elevated NIHSS scores. This finding not only enhances the spatial accuracy of the lesion map but also underscores its clinical relevance. CONCLUSION: This study underscores the significance of exploring complementary LSM approaches to investigate the association between brain lesions and stroke outcomes. By utilizing multiple methods, we can increase the robustness of our results, effectively addressing and neutralizing potential spatial bias introduced by each individual method. Such an approach holds promise for enhancing our understanding of stroke pathophysiology and optimizing patient care strategies.

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BACKGROUND: Low rates of COVID-19 vaccination remain a substantial public health challenge. Despite early successes, vaccinations of Alaskans trail the US average, drawing attention to the need for better-designed and targeted vaccine confidence interventions. Our objective was to assess levels of community trust and theory-driven predictors of vaccination status to inform the design of future programs. METHODS: We conducted a cross-sectional, telephone-based survey of 940 Alaskan adults between May and June 2022. Data were collected on vaccination status (including initial vaccination and receipt of booster shots), trust in local community members, demographic characteristics, and thematic questions designed using the Capability, Opportunity, Motivation - Behavior (COM-B) model to examine possible predictors (barriers/facilitators) of vaccination status. FINDINGS: Among those who are not fully vaccinated and boosted, we observe significantly lower trust placed in many immediate community members, especially health workers (e.g., doctors, nurses, specialty care physicians, health administrators). Firefighters and emergency medical technicians enjoy the most community trust, followed by medical professionals. Among those who received only a primary vaccine series, we find that perceptions of whether close friends are vaccinated, a sense of professional responsibility, and age were the strongest predictors vaccination status. Among the unvaccinated, we find significant predictive power from the same variables, as well as perceptions of whether family members are vaccinated, perceived risks from non-vaccination and whether vaccination is a healthy choice. CONCLUSIONS: These findings will help inform the design and targeting of future vaccine promotion interventions to adult populations in Alaska. Interventions that leverage reflective motivation and social opportunity domains of the COM-B framework may be most effective. Local community members including firefighters and emergency medical technicians, as well as medical professionals may be perceived as the most trustworthy and influential messengers among those who are not fully vaccinated and boosted.

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We sought to assess the effects of repeated cold-water immersions (CWI) on respiratory, metabolic, and sympathoadrenal responses to graded exercise in hypoxia. Sixteen (2 female) participants (age: 21.2 ± 1.3 years; body fat: 12.3 ± 7.7%; body surface area 1.87 ± 0.16 m2, VO2peak: 48.7 ± 7.9 mL/kg/min) underwent 6 CWI in 12.0 ± 1.2 °C. Each CWI was 5 min, twice daily, separated by ≥4 h, for three consecutive days, during which metabolic data were collected. The day before and after the repeated CWI intervention, participants ran in normobaric hypoxia (FIO2 = 0.135) for 4 min at 25%, 40%, 60%, and 75% of their sea level peak oxygen consumption (VO2peak). CWI had no effect on VO2 (p > 0.05), but reduced the VE (CWI #1: 27.1 ± 17.8 versus CWI #6: 19.9 ± 12.1 L/min) (p < 0.01), VT (CWI #1: 1.3 ± 0.4 vs CWI #6: 1.1 ± 0.4 L) (p < 0.01), and VE:VO2 (CWI #1: 53.5 ± 24.1 vs CWI #6: 41.6 ± 20.5) (p < 0.01) during subsequent CWI. Further, post exercise plasma epinephrine was lower after CWI compared to before (103.3 ± 43.1; 73.4 ± 34.6 pg/mL) (p = 0.03), with no change in pre-exercising values (75.4 ± 30.7; 72.5 ± 25.9 pg/mL). While these changes were noteworthy, it is important to acknowledge there were no changes in pulmonary (VE, VT, and VE:VO2) or metabolic (VO2, SmO2, and SpO2) variables across multiple hypoxic exercise workloads following repeated CWI. CWI habituated participants to cold water, but this did not lead to adaptations during exercise in normobaric hypoxia.

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Rationale & Objective: Despite guidelines calling to improve physical activity in older adults, and evidence suggesting that prekidney transplant physical function is highly associated with posttransplant outcomes, only a small percentage of older patients treated with dialysis are engaged in structured exercise. We sought to elucidate barriers and facilitators of exercise among older adults treated with dialysis awaiting transplant and their care partners. Study Design: Individual, in-depth, cognitive interviews were conducted separately for patients and care partners through secure web-conferencing. Setting & Participants: Twenty-three patients (≥50 years of age, treated with dialysis from the University of San Francisco kidney transplantation clinic, with a short physical performance battery of ≤10) and their care partners. Analytical Approach: All audio interviews were transcribed verbatim. Three investigators independently coded data and performed qualitative thematic content. The interview guide was updated iteratively based on the Capability Opportunity Motivation Behavior model. Results: Patients' median age was 60 years (57 ± 63.5) and care partners' median ages was 57 years (49.5 ± 65.5). Thirty-nine percent of patients and 78% of care partners were female, 39% of patients and 30% of care partners self-identified as African American, and 47% of dyads were spouse or partner relationships. Major themes for barriers to pretransplant exercise included lack of understanding of an appropriate regimen, physical impairments, dialysis schedules, and safety concerns. Major facilitators included having individualized or structured exercise programs, increasing social support for patients and care partners, and motivation to regain independence or functionality or to promote successful transplantation. Limitations: Participants geographically limited to Northern California. Conclusions: Although patients and care partners report numerous barriers to pretransplant exercise and activity, they also reported many facilitators. An individualized, structured, home-based exercise program could circumvent many of the reported barriers and allow older patients to improve pretransplant physical function.

Although exercise can improve the fitness of older adults treated with dialysis for kidney transplantation and reduce posttransplant complications, many such individuals do not exercise. We sought to elicit perspectives on barriers and facilitators to prekidney transplant exercises from older adults treated with dialysis and their care partners. We found that although patients and care partners had unique perspectives, they shared many barriers (such as physical and/or cognitive impairment, difficulty scheduling around dialysis, lack of guidance on exercise, and reduced exercise motivation related to dialysis) and several facilitators (such as desire to regain functionality and participate in life and motivation for successful transplantation). A shared interest among patients and care partners in joint participation in structured and home-based exercise may represent a tool to overcome barriers to pretransplant exercise.

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Respiratory syncytial virus (RSV) is a significant global health concern and major cause of hospitalization, particularly among infants and older adults. The clinical impact of RSV is well characterized in infants; however, in many countries, the burden and risk of RSV in older populations are overlooked. In Latin America, there are limited data on RSV epidemiology and disease management in older adults. Therefore, the impact of RSV in this region needs to be addressed. Here, current insights on RSV infections in older populations in Latin America, including those with underlying health conditions, are discussed. We also outline the key challenges limiting our understanding of the burden of RSV in Latin America in a worldwide context and propose an expert consensus to improve our understanding of the burden of RSV in the region. By so doing, we aim to ultimately improve disease management and outcomes of those at risk and to alleviate the impact on healthcare systems.A graphical plain language summary is available with this article.