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In September 2020, the US National Institutes of Health (NIH) allocated $12 million to support engagement with historically marginalized communities hardest hit by COVID-19. The award was designed to mobilize community-engagement in pandemic response, and to support partnerships as part of the NIH Community Engagement Alliance (CEAL) Against COVID-19 Disparities. All aspects of the award were fast-tracked, and NIH utilized a ‘more flexible’ funding mechanism (OTA) to facilitate swift distribution of funds. In this paper, we draw upon an analysis of findings from a 2021 survey conducted with 11 California CEAL sites representing urban and rural settings, private and public universities, and established and new community partners and qualitative analysis of 2020–2022 site-wide meeting minutes. We describe the challenges posed at the federal (e.g. NIH funding), university, and community–university partnership levels as well as opportunities and creative workarounds. Challenges include delays in subcontracts and payments to community partners that undermined trust and reproduced unequal and hierarchical power relationships. We build upon our findings and collective experience to propose a framework for decolonized fiscal relationships between universities and community partners which contains key recommendations for funders, universities, and community partners.

IntroductionMilitary personnel and local civilians at various deployment locations are plagued with serious health conditions. Evidence points to burn pit emissions as the cause of these pathologies; however, similar diseases are also caused by environmental exposures, smoking, genetic predispositions, or other comorbidities. Burn pits, which are large smoldering piles of refuse ignited with jet or diesel fuel, contain human and medical waste as well as paint, plastics, ammunition, and other materials—each of which can be attributed to health concerns in other industrial settings. Here we compare various pathologies attributable to toxic aerosol exposures and discuss distinct pathologies that may be linked to burn pit exposures.ObjectivesWe performed a literature review where we provide information on toxic exposures that may pose relevance to burn pit exposure and furthermore, highlight what is already known about burn pit exposures and what steps need to be taken to diagnose and correlate certain respiratory pathologies to chronic exposure from overseas burn pits.Data sourcesWe conducted searches through PubMed and Google Scholar to determine where gaps in our knowledge of burn pit exposure lie. Thorough review on jet-fuel properties and particulate matter were performed as supporting evidence of potential toxins from burn pit emissions.ResultsTo date, studies on burn pit emissions consist mainly of systematic reviews and discussions to address the problem, with very few acute-exposure studies and little to no chronic-exposure studies. We found that symptoms range from respiratory pathologies to neurological deficits, but treatment has been limited as medical facilities, such as the Veterans Administration (VA), require proof that a condition is service-connected.ConclusionsTo determine the effects of burn pit exposure on humans, chronic exposure to mimicked burn pit emissions is necessary to draw definitive conclusions between phenotypic differences in pathologies linked to exposure. By determining phenotypic differences, conclusions can be made about the pathologic origins, potentially leading to future diagnoses and treatments for veterans and affected civilians.

Known for their distinct antigen-sampling abilities, microfold cells, or M cells, have been well characterized in the gut and other mucosa including the lungs and nasal-associated lymphoid tissue (NALT). More recently, however, they have been identified in tissues where they were not initially suspected to reside, which raises the following question: what external and internal factors dictate differentiation toward this specific role? In this discussion, we will focus on murine studies to determine how these cells are identified (e.g., markers and function) and ask the broader question of factors triggering M-cell localization and patterning. Then, through the consideration of unconventional M cells, which include villous M cells, Type II taste cells, and medullary thymic epithelial M cells (microfold mTECs), we will establish the M cell as not just a player in mucosal immunity but as a versatile niche cell that adapts to its home tissue. To this end, we will consider the lymphoid structure relationship and apical stimuli to better discuss how the differing cellular programming and the physical environment within each tissue yield these cells and their unique organization. Thus, by exploring this constellation of M cells, we hope to better understand the multifaceted nature of this cell in its different anatomical locales.

The Salton Sea is a drying salt lake in an arid region with high aerosol particulate-matter concentrations. This region is plagued by a high incidence of asthma, attributed in part to the aerosols surrounding the Sea. But the connection between the Sea and asthma may be more than simple calculations of dust concentrations. While dusts might contain toxic substances that impact the lungs of residents, the complex dynamics related to the environmental degradation of the Salton Sea may be generating additional toxins relevant to public health, such as microcystins produced by algal blooms. This collection of pollutants may be driving inflammatory responses in the lungs of residents through multiple mechanisms. As such, examination of the full range of potential environmental triggers of lung inflammation promises to yield a better understanding of key mechanisms driving the high incidence of asthma in local residents. Our discussion provides a perspective aiming to re-frame the issue in the context of the historical theory of “miasma” and the linkages between environmental change and health impacts.

Abstract Background Engineered vaccine proteins incorporating both antigen and adjuvant components are constructed with the aim of combining functions to induce effective protective immunity. Bacterial flagellin is a strong candidate for an engineered vaccine scaffold as it is known to provide adjuvant activity through its TLR5 and inflammasome activation. Moreover, polymerized flagellin filaments can elicit a more robust immunoglobulin response than monomeric flagellin, and the multimeric antigen form can also promote T cell-independent antibody responses. Here, we aim to produce and test a covalently stabilized polymerized flagellar filament, providing additional immune efficacy through stabilization of its polymeric filament structure, as well as stabilization for long-term storage. Results Computational modeling of monomer packing in flagellin filaments helped identify amino acids with proximity to neighboring flagella protofilaments. Paired cysteine substitutions were made at amino acids predicted to form inter-monomer disulfide cross-links, and these substitutions were capable of forming flagella when transfected into a flagellin-negative strain of Salmonella enterica subspecies Typhimurium. Interestingly, each paired substitution stabilized different helical conformational polymorphisms; the stabilized filaments lost the ability to transition between conformations, reducing bacterial motility. More importantly, the paired substitutions enabled extensive disulfide cross links and intra-filament multimer formation, and in one of the three variants, permitted filament stability in high acidic and temperature conditions where wild-type filaments would normally rapidly depolymerize. In addition, with regard to potential adjuvant activity, all crosslinked flagella filaments were able to induce wild-type levels of epithelial NF-κB in a cell reporter system. Finally, bacterial virulence was unimpaired in epithelial adherence and invasion, and the cysteine substitutions also appeared to increase bacterial resistance to oxidizing and reducing conditions. Conclusions We identified amino acid pairs, with cysteine substitutions, were able to form intermolecular disulfide bonds that stabilized the resulting flagellar filaments in detergent, hydrochloric acid, and high temperatures while retaining its immunostimulatory function. Flagellar filaments with disulfide-stabilized protofilaments introduce new possibilities for the application of flagella as a vaccine adjuvant. Specifically, increased stability and heat tolerance permits long-term storage in a range of temperature environments, as well as delivery under a range of clinical conditions.

Respiratory illnesses, such as bronchitis, emphysema, asthma, and COVID-19, substantially remodel lung tissue, deteriorate function, and culminate in a compromised breathing ability. Yet, the structural mechanics of the lung is significantly understudied. Classical pressure-volume air or saline inflation studies of the lung have attempted to characterize the organ’s elasticity and compliance, measuring deviatory responses in diseased states; however, these investigations are exclusively limited to the bulk composite or global response of the entire lung and disregard local expansion and stretch phenomena within the lung lobes, overlooking potentially valuable physiological insights, as particularly related to mechanical ventilation. Here, we present a method to collect the first non-contact, full-field deformation measures of ex vivo porcine and murine lungs and interface with a pressure-volume ventilation system to investigate lung behavior in real time. We share preliminary observations of heterogeneous and anisotropic strain distributions of the parenchymal surface, associative pressure-volume-strain loading dependencies during continuous loading, and consider the influence of inflation rate and maximum volume. This study serves as a crucial basis for future works to comprehensively characterize the regional response of the lung across various species, link local strains to global lung mechanics, examine the effect of breathing frequencies and volumes, investigate deformation gradients and evolutionary behaviors during breathing, and contrast healthy and pathological states. Measurements collected in this framework ultimately aim to inform predictive computational models and enable the effective development of ventilators and early diagnostic strategies.

Bacterial infections associated with implanted medical devices represents a healthcare crisis due to their persistence, antibiotic tolerance, and immune avoidance. Indwelling devices are rapidly coated with host plasma and extracellular matrix proteins which can then be exploited by bacterial pathogens for adherence and subsequent biofilm development. Our understanding of the host-pathogen interface that determines the fate of biofilm-mediated infections is limited to the experimental models employed by laboratories studying these organisms. Current in vivo models of biofilm-mediated infection, while certainly useful, are typically limited to end-point analyses of bacterial burden enumeration, immune cell profiling, and cytokine/chemokine analysis. Thus, with these models, the complex, real-time assessment of biofilm development and innate immune cell activity remains imperceptible. Here, we describe a novel murine biofilm infection model employing time-lapse intravital multiphoton microscopy which permits concurrent and real-time visualization of Staphylococcus aureus biofilm formation and immune cell activity. Using cell tracking, we found that S. aureus biofilms impede neutrophil chemotaxis, redirecting their migration patterns to prevent biofilm invasion. This approach is the first to directly examine device-associated biofilm development and host-pathogen interactions and will serve to both further our understanding of infection development and help reveal the effects of future antibiofilm treatment strategies.

M cells are specialized intestinal epithelial cells that provide the main machinery for sampling luminal microbes for mucosal immune surveillance. M cells are usually found in the epithelium overlying organized mucosal lymphoid tissues, but studies have identified multiple distinct lineages of M cells that are produced under different conditions, including intestinal inflammation. Among these lineages there is a common morphology that helps explain the efficiency of M cells in capturing luminal bacteria and viruses; in addition, M cells recruit novel cellular mechanisms to transport the particles across the mucosal barrier into the lamina propria, a process known as transcytosis. These specializations used by M cells point to a novel engineering of cellular machinery to selectively capture and transport microbial particles of interest. Because of the ability of M cells to effectively violate the mucosal barrier, the circumstances of M cell induction have important consequences. Normal immune surveillance insures that transcytosed bacteria are captured by underlying myeloid/dendritic cells; in contrast, inflammation can induce development of new M cells not accompanied by organized lymphoid tissues, resulting in bacterial transcytosis with the potential to amplify inflammatory disease. In this review, we will discuss our own perspectives on the life history of M cells and also raise a few questions regarding unique aspects of their biology among epithelia.

Continuous exposure to aerosolized fine (particle size ≤2.5 µm) and ultrafine (particle size ≤0.1 µm) particulates can trigger innate inflammatory responses in the lung and brain depending on particle composition. Most studies of manmade toxicants use inhalation exposure routes, whereas most studies of allergens use soluble solutions administered via intranasal or injection routes. Here, we tested whether continuous inhalation exposure to aerosolized Alternaria alternata particulates (a common fungal allergen associated with asthma) would induce innate inflammatory responses in the lung and brain. By designing a new environmental chamber able to control particle size distribution and mass concentration, we continuously exposed adult mice to aerosolized ultrafine Alternaria particulates for 96 hr. Despite induction of innate immune responses in the lung, induction of innate immune responses in whole brain samples was not detected by quantitative polymerase chain reaction or flow cytometry. However, exposure did trigger decreases in Arginase 1, inducible nitric oxide synthase, and tumor necrosis factor alpha mRNA in the brainstem samples containing the central nervous system respiratory circuit (the dorsal respiratory group, ventral respiratory group, and the pre-Bötzinger and Bötzinger complexes). In addition, a significant decrease in the percentage of Toll-like receptor 2-expressing brainstem microglia was detected by flow cytometry. Histologic analysis revealed a significant decrease in Iba1 but not glial fibrillary acidic protein immunoreactivity in both the brainstem and the hippocampus. Together these data indicate that inhalation exposure to a natural fungal allergen under conditions sufficient to induce lung inflammation surprisingly causes reductions in baseline expression of select innate immune molecules (similar to that observed during endotoxin tolerance) in the region of the central nervous system controlling respiration.

Abstract Climate change is currently one of humanity’s greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries.

Overweight individuals often struggle to lose weight. While previous studies established goal setting as an effective strategy for weight loss, little is known about the effects of numeric goal precision. The present research investigated whether and how the precision of weight loss goals—the number of trailing zeros—impacts a goal’s effectiveness. In two preregistered, longitudinal experiments, we contrasted competing predictions as to whether precise (e.g., 2.923 kg) or round (e.g., 3.000 kg) goals are more effective compared to a waiting control condition. In Experiment 1 (N = 121), participants in the two goal conditions lost more weight compared to the control condition—an effect that was mainly driven by precise (rather than round) goals. In Experiment 2 (N = 150), we sought to replicate this effect but found no significant weight loss differences. An individual participant data (IPD) meta-analysis across both experiments revealed that (a) the goal groups jointly lost more weight than the waiting control group and (b) the precise and round goal groups did not differ in weight loss success. An IPD-based multiple mediation analysis showed that healthier eating, but not physical exercise accounted for goal-setting-induced weight loss. We discuss possible explanations for the null findings in Experiment 2 and highlight directions for future research.

Taking the stairs vs. an elevator generate benefits for the individual by increasing overall physical activity, health, and wellbeing. In the present paper, we report two pre-registered field intervention studies that examine how health message interventions can motivate individuals to change their behavior. We empirically contrasted opposing predictions from the literature as to whether numerically round (60.00%) or precise (61.87%) health messages are more effective in causing people to use the stairs over taking the elevator. Both interventions were compared to a control condition (no-health message). Contrary to our hypotheses and extant findings, both intervention studies did not produce a significant positive effect of the interventions relative to the control condition. In recent years such null findings have received increasingly more appreciation, particularly in the light of evident downsides of file-drawered studies. We discuss a number of moderating factors that may determine when and why nudging interventions are (in-) effective (e.g., a priori behavioral prevalence, pre-established habits, ceiling effects, and building infrastructure), as well as limitations and avenues for future research.

The present study aims for a better understanding of how individuals’ behavior in monetary price negotiations differs from their behavior in bartering situations. Two contrasting hypotheses were derived from endowment theory and current negotiation research to examine whether negotiators are more susceptible to anchoring in price negotiations versus in bartering transactions. In addition, past research found that cues of coldness enhance cognitive control and reduce anchoring effects. We attempted to replicate these coldness findings for price anchors in a distributive negotiations scenario and to illuminate the potential interplay of coldness priming with a price versus bartering manipulation. Participants (N = 219) were recruited for a 2 × 2 between-subjects negotiation experiment manipulating (1) monetary focus and (2) temperature priming. Our data show a higher anchoring susceptibility in price negotiations than in bartering transactions. Despite a successful priming manipulation check, coldness priming did not affect participants’ anchoring susceptibility (nor interact with the price/bartering manipulation). Our findings improve our theoretical understanding of how the focus on negotiation resources frames economic transactions as either unidirectional or bidirectional, and how this focus shapes parties’ susceptibility to the anchoring bias and negotiation behavior. Implications for theory and practice are discussed.

Duplication of the gallbladder is a rare congenital anomaly of the biliary system. We herein present a case of a 9-month-old full-term female with a prenatally identified gallbladder duplication cyst managed via laparoscopic excision.

Herein, we present a protocol for culturing patient-derived organoids (PDOs) of cervical cancer that includes workflows for tumor biopsy/resection tissue and cytobrush-sampled cells. We describe steps for PDO culture initiation, including rinsing, gentle dissociation, Lymphoprep separation, and cell assessment, as well as seeding cells from surgical and cytobrush tissue digestion. We then provide guidance on PDO maintenance and passage and techniques for producing conditioned medium. Overall, this protocol serves as a valuable guide for establishing and maintaining cervical cancer PDOs. For complete details on the use and execution of this protocol, please refer to Colbert et al. 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Preschool-aged children have among the highest burden of acute wheeze. We investigated differences in healthcare use, treatment and outcomes for recurrent wheeze/asthma in preschoolers from different ethno-socioeconomic backgrounds., Methods: Retrospective cohort study using data from the Clinical Practice Research Datalink linked to Hospital Episode Statistics in England. We reported number of acute presentations and hospitalisations stratified by index of multiple deprivation (IMD) and ethnicity; and factors associated with treatment non-escalation, and hospitalisation rates using multivariable logistic and Poisson regression models., Results: 194 291 preschool children were included. In children not trialled on asthma preventer medications, children from the most deprived IMD quintile (adjusted OR 1.67; 95% CI 1.53 to 1.83) and South Asian (1.77; 1.64 to 1.91) children were more likely to have high reliever usage and where specialist referral had not occurred, the odds of referral being indicated was higher in the most deprived quintile (1.39; 1.28 to 1.52) and South Asian (1.86; 1.72 to 2.01) children compared with the least deprived quintile and white children, respectively.Hospitalisation rates for wheeze/asthma were significantly higher in children from the most deprived quintile (adjusted IRR 1.20; 95% CI 1.13 to 1.27) compared with the least, and in South Asian (1.57; 1.44 to 1.70) and black (1.32; 1.22 to 1.42) compared with white children., Conclusions: We identified inequalities in wheeze/asthma treatment and morbidity in preschool children from more deprived, and non-white backgrounds. A multifaceted approach to tackle health inequality at both the national and local levels, which includes a more integrated and standardised approach to treatment, is needed to improve health outcomes in children with preschool wheeze/asthma., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare the following: DL and CL receive support from the National Institute for Health and Care Research (NIHR). DL has also received an institutional research grant from the Midlands Asthma and Allergy Research Association (MAARA). HP holds institutional research grants from NIHR and Asthma UK unrelated to this publication and has received personal fees from Teva Pharmaceuticals and Sandoz UK. Additionally, HP has received travel expense payments from the European Respiratory Society (ERS). JKQ has received institutional grants from the Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Asthma+Lung UK, and Astra Zeneca (AZ); and personal fees from GSK, Evidera, Chiesi, AZ, and Insmed. EAG has received institutional grants from Gilead, Circassia, Chiesi, Propellar Health, Helicon Health, Adherium Ltd, and AZ; and personal fees from Circassia and Sanofi. SS and CG had no competing interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chemoradiation (CRT) may modulate the immune milieu as an in-situ vaccine. Rapid dose delivery of brachytherapy has unclear impact on T-cell repertoires. HPV-associated cancers express viral oncoproteins E6/E7, which enable tracking antigen/tumor-specific immunity during CRT., Methods: Thirteen cervical cancer patients on a multi-institutional prospective protocol from 1/2020-1/2023 underwent standard-of-care CRT with pulsed-dose-rate brachytherapy boost (2 fractions). Cervix swabs at various timepoints underwent multiplex DNA deep sequencing of the TCR-β/CDR3 region with immunoSEQ. Separately, HPV-responsive T-cell clones were also expanded ex vivo. Statistical analysis was via Mann-Whitney-U., Results: TCR productive clonality, templates, frequency, or rearrangements increased post-brachytherapy in 8 patients. Seven patients had E6/E7-responsive evolution over CRT with increased productive templates (ranges: 1.2-50.2 fold-increase from baseline), frequency (1.2-1.7), rearrangements (1.2-40.2), and clonality (1.2-15.4). Five patients had HPV-responsive clonal expansion post-brachytherapy, without changes in HPV non-responsive clones. Epitope mapping revealed VDJ rearrangements targeting cervical cancer-associated antigens in 5 patients. The only two patients with disease recurrence lacked response in all metrics. A lack of global TCR remodeling correlated with worse recurrence-free survival, p = 0.04., Conclusion: CRT and brachytherapy alters the cervical cancer microenvironment to facilitate the expansion of specific T-cell populations, which may contribute to treatment efficacy., (Copyright © 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Tumor microbiota can produce active metabolites that affect cancer and immune cell signaling, metabolism, and proliferation. Here, we explore tumor and gut microbiome features that affect chemoradiation response in patients with cervical cancer using a combined approach of deep microbiome sequencing, targeted bacterial culture, and in vitro assays. We identify that an obligate L-lactate-producing lactic acid bacterium found in tumors, Lactobacillus iners, is associated with decreased survival in patients, induces chemotherapy and radiation resistance in cervical cancer cells, and leads to metabolic rewiring, or alterations in multiple metabolic pathways, in tumors. Genomically similar L-lactate-producing lactic acid bacteria commensal to other body sites are also significantly associated with survival in colorectal, lung, head and neck, and skin cancers. Our findings demonstrate that lactic acid bacteria in the tumor microenvironment can alter tumor metabolism and lactate signaling pathways, causing therapeutic resistance. Lactic acid bacteria could be promising therapeutic targets across cancer types., Competing Interests: Declaration of interests L.E.C. reports grants from American Society for Clinical Oncology, Radiology Society of North America, National Institutes of Health, and MD Anderson Cancer Center during the conduct of the study. A.J. reports personal fees from Genentech during the conduct of the study, as well as personal fees from Genentech outside the submitted work. L.L. reports other support from AstraZeneca and Pfizer, and grants from NCI outside the submitted work. J.A.W. reports other support from Micronoma during the conduct of the study, as well as other support from Imedex, Dava Oncology, Illumina, and PeerView outside the submitted work. P.O. reports Faculty grant/research support from Merck Sharp and Dohme Corp, Deinove Pharmaceuticals, Summit Pharmaceuticals, Melinta Pharmaceuticals, and Napo Pharmaceutical, in addition to consultant work with Napo Pharmaceutical, Ferring Pharmaceutical, Summit Pharmaceutical, and SNIPR Biome Company, all outside of the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Complementing recognition of biomedical phenotypes, a primary care approach to asthma care recognizes diversity of disease, health beliefs, and lifestyle at a population and individual level., Areas Covered: We review six aspects of personalized care particularly pertinent to primary care management of asthma: personalizing support for individuals living with asthma; targeting asthma care within populations; managing phenotypes of wheezy pre-school children; personalizing management to the individual; meeting individual preferences for provision of asthma care; optimizing digital approaches to enhance personalized care., Expert Opinion: In a primary care setting, personalized management and supporting individuals to live with asthma extend beyond the contemporary concepts of biological phenotypes and pharmacological 'treatable traits' to encompass evidence-based tailored support for self-management, and delivery of patient-centered care including motivational interviewing. It extends to how we organize clinical practiceand the choices provided in mode of consultation. Diagnostic uncertainty due to recognition of phenotypes of pre-school wheeze remains a challenge for primary care. Digital health can support personalized management, but there are concerns about increasing inequities. This broad approach reflects the traditionally holistic ethos of primary care ('knowing their patients and understanding their communities'), but the core concepts resonate with all healthcare.

Common diagnoses associated with right upper quadrant and epigastric pain include cholecystitis, peptic ulcer disease (PUD), biliary colic, gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). Multiseptate gallbladder is a rare congenital anomaly that can cause symptoms of biliary colic, however it may present with atypical symptoms, which can prolong definitive diagnosis and treatment. We present a case of multiseptate gallbladder in a 21-year-old female who initially presented with GERD and IBS. After multiple failed treatment regimens for IBS, she ultimately was found to have multiseptate gallbladder and was successfully treated with cholecystectomy., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2022.)

Background: We sought to determine the association between appendicular adiposity and hypertension, with the purpose of better understanding the role of body fat distribution on blood pressure (BP)., Methods: We included 7411 adults aged 20 to 59 who were not taking antihypertensives and without cardiovascular disease from the 2011 to 2018 National Health and Nutrition Examination Surveys. Leg & arm adiposity, determined via dual-energy X-ray absorptiometry scans, was defined as percent of total body fat present in legs/arms (leg/total%, arm/total%). Measures were categorized into sex-specific tertiles. We estimated change in BP and odds ratios (ORs) of hypertension (BP ≥ 130/80) and hypertension subtypes using multivariable, survey design-adjusted linear & logistic regression, respectively., Results: Of the participants, 49% were female, the average (standard deviation) age was 37.4 (0.3) years, and 24% had hypertension. Those in the highest tertile (T3) of leg/total% had 30% decreased adjusted ORs (aOR) of hypertension compared to the lowest tertile (T1; aOR, 0.70; 95% confidence interval [95% CI], 0.55-0.89). This association was not significant for arm/total% (0.89, 0.68-1.17). T3 of leg/total% was associated with 49% lower, 41% lower, and unchanged relative odds of isolated diastolic hypertension (IDH), systolic-diastolic hypertension (SDH), and isolated systolic hypertension (ISH) compared to T1 (IDH: 0.51, 0.37-0.70; SDH: 0.59, 0.43-0.80; ISH: 1.06, 0.70-1.59). For every 10% increase in leg/total%, diastolic BP decreased by an adjusted mean 3.5 mmHg (95% CI, - 4.8 to - 2.2) in males and 1.8 mmHg (95% CI, - 2.8 to - 0.8) in females (P < 0.001 for both)., Conclusions: A greater proportional distribution of fat around the legs is inversely, independently associated with hypertension, and more specifically, diastolic hypertension (IDH and SDH)., (© 2021. The Author(s).)

Objective: To identify risk factors for asthma attacks and poor asthma control in children aged 5-16 years., Methods: Prospective observational cohort study of 460 children with asthma or suspected asthma from 10 UK general practices.Gender, age, ethnicity, body mass index, practice deprivation decile, spirometry and fraction of exhaled nitric oxide (FeNO) were recorded at baseline. Asthma control scores, asthma medication ratio (AMR) and the number of asthma attacks were recorded at baseline and at 6 months.The above independent variables were included in binary multiple logistic regression analyses for the dependent variables of: (1) poor symptom control and (2) asthma attacks during follow-up., Results: Poor symptom control at baseline predicted poor symptom control at 6 months (OR 4.4, p=0.001), while an increase in deprivation decile (less deprived) was negatively associated with poor symptom control at 6 months (OR 0.79, p=0.003). Higher FeNO levels (OR 1.02, p<0.001) and a recent history of asthma attacks (OR 2.03, p=0.02) predicted asthma attacks during follow-up. Asian ethnicity was associated with a lower OR for a future attack (OR 0.32, p=0.02).A decrease in AMR was also associated with an increased OR for future asthma attacks (OR 2.99, p=0.003) when included as an independent variable., Conclusions: We identified risk factors for poor symptom control and asthma attacks in children. Routine assessment of these factors should form part of the asthma review to identify children at an increased risk of adverse asthma-related events., Competing Interests: Competing interests: EAG: consultancy work for Boehringer Ingelheim in November 2016 and Anaxsys in July 2018 with money paid to the institution (University of Leicester), investigator led research grant from Circassia and Gilead. Research collaboration with Medimmune. Travel grants from Vertex., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The National Institute for Health and Care Excellence recommends the use of spirometry and measuring the fraction of exhaled nitric oxide (FeNO) as part of the diagnostic work-up for children with suspected asthma, and spirometry for asthma monitoring, across all care settings. However, the feasibility and acceptability of these tests within primary care are not known., Aim: To investigate the feasibility, acceptability, training, and capacity requirements of performing spirometry and FeNO testing in children managed for asthma in UK primary care., Design and Setting: Prospective observational study involving 10 general practices in the East Midlands, UK, and 612 children between 2016 and 2017., Method: Training and support to perform spirometry and FeNO in children aged 5 to 16 years were provided to participating practices. Children on the practice's asthma registers, and those with suspected asthma, were invited for a routine asthma review. Time for general practice staff to achieve competencies in performing and/or interpreting both tests, time to perform the tests, number of children able to perform the tests, and feedback on acceptability were recorded., Results: A total of 27 general practice staff were trained in a mean time of 10.3 (standard deviation 2.7) hours. Usable spirometry and FeNO results were obtained in 575 (94%) and 472 (77%) children respectively. Spirometry is achievable in the majority of children aged ≥5 years, and FeNO in children aged ≥7 years. All of the staff and 97% of families surveyed provided positive feedback for the tests., Conclusion: After training, general practice staff obtained quality spirometry and FeNO data from most children tested. Testing was acceptable to staff and families. The majority of general practice staff reported that spirometry helped them to manage children's asthma better., (© British Journal of General Practice 2020.)

The purpose of this cross-sectional, secondary analysis was to determine the association between BMI & lipids and hypertension subtype in U.S. and Indian adults. Obese BMI was significantly associated with isolated diastolic hypertension (IDH) compared to low/normal BMI (relative risk ratio [95% CI]; U.S.: 4.33 [2.88,6.52]; India: 2.51 [2.41,2.60]). Furthermore, BMI was more strongly associated with IDH than other hypertension subtypes in U.S. and non-obese Indian adults. In obese Indian adults, we observed higher odds of isolated systolic hypertension until the 6th decade, and systo-diastolic hypertension thereafter. Triglyceride levels were associated with IDH in U.S. adults (1.94 [1.43,2.63])., Competing Interests: Conflicts of interest The authors declare that they have no competing interests., (Copyright © 2020 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)