Common ground: shared risk factors for type 1 diabetes and celiac disease.

Risk factors for most autoimmune diseases are multifactorial genetic variants modified by environmental risk factors. Type 1 diabetes and celiac disease share high-risk HLA haplotypes, and the prevalence of both diseases has increased in many regions during the past half century. Unknown environmental factors are suspected to have increased the disease penetrance. Celiac disease depends on immune responses to dietary gluten, whereas the environmental risk factors for type 1 diabetes are not yet clear. Here, we consider the shared heritable genetic factors and review evidence of the dietary and microbial exposures, particularly in early life, that might influence the pathogenesis of one or both diseases. A deeper mechanistic understanding of the environmental factors responsible for increased risk of these diseases should provide opportunities to manipulate exposure in children carrying defined risk markers and thus prevent and attenuate disease, as well as to identify new therapeutic strategies for patients.

Cracking the type 1 diabetes code: Genes, microbes, immunity, and the early life environment.

Type 1 diabetes (T1D) results from a complex interplay of genetic predisposition, immunological dysregulation, and environmental triggers, that culminate in the destruction of insulin-secreting pancreatic ß cells. This review provides a comprehensive examination of the multiple factors underpinning T1D pathogenesis, to elucidate key mechanisms and potential therapeutic targets. Beginning with an exploration of genetic risk factors, we dissect the roles of human leukocyte antigen (HLA) haplotypes and non-HLA gene variants associated with T1D susceptibility. Mechanistic insights gleaned from the NOD mouse model provide valuable parallels to the human disease, particularly immunological intricacies underlying ß cell-directed autoimmunity. Immunological drivers of T1D pathogenesis are examined, highlighting the pivotal contributions of both effector and regulatory T cells and the multiple functions of B cells and autoantibodies in ß-cell destruction. Furthermore, the impact of environmental risk factors, notably modulation of host immune development by the intestinal microbiome, is examined. Lastly, the review probes human longitudinal studies, unveiling the dynamic interplay between mucosal immunity, systemic antimicrobial antibody responses, and the trajectories of T1D development. Insights garnered from these interconnected factors pave the way for targeted interventions and the identification of biomarkers to enhance T1D management and prevention strategies.

Acetic Acid Enables Molecular Enumeration of Mycobacterium tuberculosis from Sputum and Eliminates the Need for a Biosafety Level 3 Laboratory.

BACKGROUND: Improved monitoring of Mycobacterium tuberculosis response to treatment is urgently required. We previously developed the molecular bacterial load assay (MBLA), but it is challenging to integrate into the clinical diagnostic laboratory due to a labor-intensive protocol required at biosafety level 3 (BSL-3). A modified assay was needed. METHODS: The rapid enumeration and diagnostic for tuberculosis (READ-TB) assay was developed. Acetic acid was tested and compared to 4 M guanidine thiocyanate to be simultaneously bactericidal and preserve mycobacterial RNA. The extraction was based on silica column technology and incorporated low-cost reagents: 3 M sodium acetate and ethanol for the RNA extraction to replace phenol-chloroform. READ-TB was fully validated and compared directly to the MBLA using sputa collected from individuals with tuberculosis. RESULTS: Acetic acid was bactericidal to M. tuberculosis with no significant loss in 16S rRNA or an unprotected mRNA fragment when sputum was stored in acetic acid at 25°C for 2 weeks or -20°C for 1 year. This novel use of acetic acid allows processing of sputum for READ-TB at biosafety level 2 (BSL-2) on sample receipt. READ-TB is semiautomated and rapid. READ-TB correlated with the MBLA when 85 human sputum samples were directly compared (R2 = 0.74). CONCLUSIONS: READ-TB is an improved version of the MBLA and is available to be adopted by clinical microbiology laboratories as a tool for tuberculosis treatment monitoring. READ-TB will have a particular impact in low- and middle-income countries (LMICs) for laboratories with no BSL-3 laboratory and for clinical trials testing new combinations of anti-tuberculosis drugs.

The effectiveness and safety of proton beam radiation therapy in children and young adults with Central Nervous System (CNS) tumours: a systematic review.

BACKGROUND: Central nervous system (CNS) tumours account for around 25% of childhood neoplasms. With multi-modal therapy, 5-year survival is at around 75% in the UK. Conventional photon radiotherapy has made significant contributions to survival, but can be associated with long-term side effects. Proton beam radiotherapy (PBT) reduces the volume of irradiated tissue outside the tumour target volume which may potentially reduce toxicity. Our aim was to assess the effectiveness and safety of PBT and make recommendations for future research for this evolving treatment. METHODS: A systematic review assessing the effects of PBT for treating CNS tumours in children/young adults was undertaken using methods recommended by Cochrane and reported using PRISMA guidelines. Any study design was included where clinical and toxicity outcomes were reported. Searches were to May 2021, with a narrative synthesis employed. RESULTS: Thirty-one case series studies involving 1731 patients from 10 PBT centres were included. Eleven studies involved children with medulloblastoma / primitive neuroectodermal tumours (n = 712), five ependymoma (n = 398), four atypical teratoid/rhabdoid tumour (n = 72), six craniopharyngioma (n = 272), three low-grade gliomas (n = 233), one germ cell tumours (n = 22) and one pineoblastoma (n = 22). Clinical outcomes were the most frequently reported with overall survival values ranging from 100 to 28% depending on the tumour type. Endocrine outcomes were the most frequently reported toxicity outcomes with quality of life the least reported. CONCLUSIONS: This review highlights areas of uncertainty in this research area. A well-defined, well-funded research agenda is needed to best maximise the potential of PBT. SYSTEMATIC REVIEW REGISTRATION: PROSPERO-CRD42016036802.

Exhaled Mycobacterium tuberculosis Predicts Incident Infection in Household Contacts.

BACKGROUND: Halting transmission of Mycobacterium tuberculosis (Mtb) by identifying infectious individuals early is key to eradicating tuberculosis (TB). Here we evaluate face mask sampling as a tool for stratifying the infection risk of individuals with pulmonary TB (PTB) to their household contacts. METHODS: Forty-six sputum-positive PTB patients in The Gambia (August 2016-November 2017) consented to mask sampling prior to commencing treatment. Incident Mtb infection was defined in 181 of their 217 household contacts as QuantiFERON conversion or an increase in interferon-γ of ≥1 IU/mL, 6 months after index diagnosis. Multilevel mixed-effects logistical regression analysis with cluster adjustment by household was used to identify predictors of incident infection. RESULTS: Mtb was detected in 91% of PTB mask samples with high variation in IS6110 copies (5.3 × 102 to 1.2 × 107). A high mask Mtb level (≥20 000 IS6110 copies) was observed in 45% of cases and was independently associated with increased likelihood of incident Mtb infection in contacts (adjusted odds ratio, 3.20 [95% confidence interval, 1.26-8.12]; P = .01), compared with cases having low-positive/negative mask Mtb levels. Mask Mtb level was a better predictor of incident Mtb infection than sputum bacillary load, chest radiographic characteristics, or sleeping proximity. CONCLUSIONS: Mask sampling offers a sensitive and noninvasive tool to support the stratification of individuals who are most infectious in high-TB-burden settings. Our approach can provide better insight into community transmission in complex environments.

Transforming Medical Education to Provide Gender-Affirming Care for Transgender and Gender-Diverse Patients: A Policy Brief.

Transgender and gender-diverse (TGD) patients experience a greater burden of health disparities compared with their heterosexual/cisgender counterparts. Some of the poorer health outcomes observed in these populations are known to be associated with the prevalence of implicit bias, bullying, emotional distress, alcoholism, drug abuse, intimate partner violence, sexually transmitted infections (eg, human immunodeficiency virus and human papilloma virus), and cancer. The TGD populations face unique barriers to receiving both routine and gender-affirming health care (acquiring hormones and gender-affirming surgeries). Additional barriers to implementing affirming care training for TGD patients are lack of expertise among medical education faculty and preceptors both in undergraduate and in graduate medical education programs. Drawing on a systematic review of the literature, we propose a policy brief aimed at raising awareness about gender-affirming care among education planners and policy makers in government and advisory bodies.

SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin.

Cancer cells elude anti-tumour immunity through multiple mechanisms, including upregulated expression of ligands for inhibitory immune checkpoint receptors. Phagocytosis by macrophages plays a critical role in cancer control. Therapeutic blockade of signal regulatory protein (SIRP)-α, an inhibitory receptor on macrophages, or of its ligand CD47 expressed on tumour cells, improves tumour cell elimination in vitro and in vivo, suggesting that blockade of the SIRPα-CD47 checkpoint could be useful in treating human cancer. However, the pro-phagocytic receptor(s) responsible for tumour cell phagocytosis is(are) largely unknown. Here we find that macrophages are much more efficient at phagocytosis of haematopoietic tumour cells, compared with non-haematopoietic tumour cells, in response to SIRPα-CD47 blockade. Using a mouse lacking the signalling lymphocytic activation molecule (SLAM) family of homotypic haematopoietic cell-specific receptors, we determined that phagocytosis of haematopoietic tumour cells during SIRPα-CD47 blockade was strictly dependent on SLAM family receptors in vitro and in vivo. In both mouse and human cells, this function required a single SLAM family member, SLAMF7 (also known as CRACC, CS1, CD319), expressed on macrophages and tumour cell targets. In contrast to most SLAM receptor functions, SLAMF7-mediated phagocytosis was independent of signalling lymphocyte activation molecule-associated protein (SAP) adaptors. Instead, it depended on the ability of SLAMF7 to interact with integrin Mac-1 (refs 18, 19, 20) and utilize signals involving immunoreceptor tyrosine-based activation motifs. These findings elucidate the mechanism by which macrophages engulf and destroy haematopoietic tumour cells. They also reveal a novel SAP adaptor-independent function for a SLAM receptor. Lastly, they suggest that patients with tumours expressing SLAMF7 are more likely to respond to SIRPα-CD47 blockade therapy.

Short-term impact of COVID-19 pandemic on low back pain: data from the PAMPA Cohort, Brazil.

BACKGROUND: To evaluate the short-term impact of COVID-19 pandemic on low back pain (LBP) outcomes in southern Brazil. METHODS: Data from the PAMPA Cohort were analyzed. Adults were recruited between June and July 2020 in the Rio Grande do Sul state using online-based strategies. Participants responded a self-reported, online questionnaire on LBP with two timepoints: before (retrospectively) and during COVID-19 pandemic. We assessed LBP experience, LBP-related activity limitation (no/yes), and LBP intensity (0 to 10 [strongest pain]). RESULTS: From a total sample of 2,321 respondents (mean age: 37.6 ± 13.5; 75.4% women), the prevalence of LBP did not change significantly from before (74.7% [95%CI 72.3; 76.9]) to the first months of pandemic (74.2% [95%CI 71.9; 76.3]). However, an increased pain levels (ß: 0.40; 95%CI 0.22; 0.58) and a higher likelihood for activity limitation due to LBP was observed (PR 1.14; 95%CI 1.01; 1.29). Longitudinal analyzes showed that age, gender, BMI, chronic diseases, physical activity, and anxiety and depression symptoms, were associated with LBP in the first pandemic months. CONCLUSION: Although the prevalence of LBP did not change at the first months of COVID-19 pandemic, LBP-induced impairment in daily activities and pain intensity was higher when compared to before the pandemic.

Physical activity during early life and the risk of all-cause mortality in midlife: findings from a birth cohort study.

BACKGROUND: The objective of this study was to examine the association between physical activity during childhood and adolescence and the risk of all-cause mortality in midlife. We analyzed data from a birth cohort (The 1958 National Child Development Survey), including births in England, Wales and Scotland. METHODS: Physical activity was assessed using questionnaires at ages 7, 11 and 16. Death certificates defined all-cause mortality. Cumulative exposure, sensitive and critical periods, and physical activity trajectory from childhood to adolescence were tested using multivariate Cox proportional hazard models. The sweep the death was confirmed was defined as the time event. RESULTS: From age 23 to 55, 8.9% of participants (n = 9398) died. Physical activity in childhood and adolescence affected the risk of all-cause mortality in midlife. In men, physical activity at ages 11 [hazard ratio (HR): 0.77; 95% confidence interval (CI): 0.60-0.98] and 16 (HR: 0.60; 95% CI: 0.46-0.78) was associated with reduced risk of all-cause mortality. In women, physical activity at age 16 (HR: 0.68; 95% CI: 0.48-0.95) was associated with reduced risk of all-cause mortality. Physical activity in adolescence eliminated the risk of all-cause mortality associated with physical inactivity in adulthood in women. CONCLUSIONS: Physical activity during childhood and adolescence was associated with reduced risk of all-cause mortality with different effects by sex.

Care seek behavior for low back pain in southern Brazil during the COVID-19 pandemic: a panel data analysis.

BACKGROUND: During the COVID-19 pandemic, people with low back pain (LBP) might have avoided seeking care for their pain. We aimed to investigate how the COVID-19 pandemic has affected LBP care seeking behavior among adults. METHODS: Data from four assessments of the PAMPA cohort were analyzed. Participants who reported experiencing LBP during wave one both before and during social restrictions (n = 1,753 and n = 1,712, respectively), wave two (n = 2,009), and wave three (n = 2,482) were included. We asked participants about sociodemographic, behavioral, and health factors and outcomes related to LBP. Poisson regression analyses were conducted, and data are presented as prevalence ratios (PR) and respective 95% confidence interval (95%CI). RESULTS: Overall, care seeking behavior decreased by half in the first months of restrictions, from 51.5% to 25.2%. Although there was an increase in care seeking behavior observed in the other two assessments (nearly 10 and 16 months after restrictions), it was insufficient to reach pre-pandemic levels. In the first months of restrictions, a similar scenario was observed for specific care, such as general practitioner and exercise professional care, with proportions of pre-pandemic levels reached after 10 and 16 months. Women were more likely to seek care for LBP 10 and 16 months after restrictions (PR 1.30 95%CI 1.11; 1.52, PR 1.22 95%CI 1.06; 1.39, respectively). Also, those participants who worked, were physically active, and reported pain-related disability and high pain levels were more likely to seek care at all time points assessed. CONCLUSION: Overall, care-seeking behavior for LBP significantly decreased in the first months of restrictions and increased in the following months; however, this behavior remained lower than pre-pandemic levels.

Systematic review and meta-analysis on population attributable fraction for physical inactivity to dementia.

INTRODUCTION: The number of cases of dementia attributable to physical inactivity remains unclear due to heterogeneity in physical inactivity definitions and statistical approaches used. METHODS: Studies that used population-based samples to estimate the population attributable fraction (PAF) of physical inactivity for dementia were included in this review. Weighted PAFs were adjusted for communality among the risk factors (i.e., inactive persons may also share other risk factors) analyzed. Values were reported as percentage (%) of cases of dementia attributable to physical inactivity. RESULTS: We included 22 studies. The overall impact of physical inactivity, defined by any criteria, on dementia ranged from 6.6% (95% CI: 3.6%, 9.6%; weighted) to 16.6% (95% CI: 14.4%, 18.9%; unweighted). Studies using the WHO criterion for physical inactivity estimated a higher unweighted impact (ß = 7.3%; 95% CI: 2.0%, 12.6%) than studies using other criteria. DISCUSSION: Conservatively, one in 15 cases of dementia may be attributable to physical inactivity, defined by any criteria.

Neutrophils Contribute to Severity of Tuberculosis Pathology and Recovery From Lung Damage Pre- and Posttreatment.

BACKGROUND: Despite microbiological cure, about 50% of tuberculosis (TB) patients have poor lung recovery. Neutrophils are associated with lung pathology; however, CD16/CD62L-defined subsets have not been studied in TB. Using flow cytometry, we monitored frequencies, phenotype, and function of neutrophils following stimulation with Mycobacterium tuberculosis (Mtb) whole cell lysate (WCL) and ESAT-6/CFP-10 fusion protein (EC) in relation to lung pathology. METHODS: Fresh blood from 42 adult, human immunodeficiency virus (HIV)-negative TB patients were analyzed pre- and post-therapy, with disease severity determined using chest radiography and bacterial load. Flow cytometry was used to monitor frequencies, phenotype, and function (generation of reactive oxygen species [ROS], together with CD11b, tumor necrosis factor, and interleukin 10 [IL-10] expression) of neutrophils following 2-hour stimulation with Mtb-specific antigens. RESULTS: Total neutrophils decreased by post-treatment compared to baseline (P = .0059); however, CD16brCD62Lbr (segmented) neutrophils increased (P = .0031) and CD16dimCD62Lbr (banded) neutrophils decreased (P = .038). Banded neutrophils were lower in patients with severe lung damage at baseline (P = .035). Following WCL stimulation, ROS from segmented neutrophils was higher in patients with low Mtb loads even after adjusting for sex (P = .038), whereas IL-10-expressing CD16dimCD62Llo cells were higher in patients with mild damage (P = .0397) at baseline. CONCLUSIONS: High ROS generation, low levels of banded neutrophils, and high levels of IL-10-expressing CD16dimCD62Llo neutrophils are associated with reduced lung pathology at diagnosis. Hence, neutrophils are potential early indicators of TB severity and promising targets for TB host-directed therapy.

Diagnostic Accuracy of the Cepheid 3-gene Host Response Fingerstick Blood Test in a Prospective, Multi-site Study: Interim Results.

BACKGROUND: The development of a fast and accurate, non-sputum-based point-of-care triage test for tuberculosis (TB) would have a major impact on combating the TB burden worldwide. A new fingerstick blood test has been developed by Cepheid (the Xpert MTB Host Response [MTB-HR] prototype), which generates a "TB score" based on messenger RNA (mRNA) expression of 3 genes. Here we describe the first prospective findings of the MTB-HR prototype. METHODS: Fingerstick blood from adults presenting with symptoms compatible with TB in South Africa, The Gambia, Uganda, and Vietnam was analyzed using the Cepheid GeneXpert MTB-HR prototype. Accuracy of the Xpert MTB-HR cartridge was determined in relation to GeneXpert Ultra results and a composite microbiological score (GeneXpert Ultra and liquid culture) with patients classified as having TB or other respiratory diseases (ORD). RESULTS: When data from all sites (n = 75 TB, 120 ORD) were analyzed, the TB score discriminated between TB and ORD with an area under the curve (AUC) of 0.94 (95% confidence interval [CI], .91-.97), sensitivity of 87% (95% CI, 77-93%) and specificity of 94% (88-97%). When sensitivity was set at 90% for a triage test, specificity was 86% (95% CI, 75-97%). These results were not influenced by human immunodeficiency virus (HIV) status or geographical location. When evaluated against a composite microbiological score (n = 80 TB, 111 ORD), the TB score was able to discriminate between TB and ORD with an AUC of 0.88 (95% CI, .83-.94), 80% sensitivity (95% CI, 76-85%) and 94% specificity (95% CI, 91-96%). CONCLUSIONS: Our interim data indicate the Cepheid MTB-HR cartridge reaches the minimal target product profile for a point of care triage test for TB using fingerstick blood, regardless of geographic area or HIV infection status.

MuLV-related endogenous retroviral elements and Flt3 participate in aberrant end-joining events that promote B-cell leukemogenesis.

During V(D)J recombination of immunoglobulin genes, p53 and nonhomologous end-joining (NHEJ) suppress aberrant rejoining of DNA double-strand breaks induced by recombinase-activating genes (Rags)-1/2, thus maintaining genomic stability and limiting malignant transformation during B-cell development. However, Rag deficiency does not prevent B-cell leukemogenesis in p53/NHEJ mutant mice, revealing that p53 and NHEJ also suppress Rag-independent mechanisms of B-cell leukemogenesis. Using several cytogenomic approaches, we identified a novel class of activating mutations in Fms-like tyrosine kinase 3 (Flt3), a receptor tyrosine kinase important for normal hematopoiesis in Rag/p53/NHEJ triple-mutant (TM) B-cell leukemias. These mutant Flt3 alleles were created by complex genomic rearrangements with Moloney leukemia virus (MuLV)-related endogenous retroviral (ERV) elements, generating ERV-Flt3 fusion genes encoding an N-terminally truncated mutant form of Flt3 (trFlt3) that was transcribed from ERV long terminal repeats. trFlt3 protein lacked most of the Flt3 extracellular domain and induced ligand-independent STAT5 phosphorylation and proliferation of hematopoietic progenitor cells. Furthermore, expression of trFlt3 in p53/NHEJ mutant hematopoietic progenitor cells promoted development of clinically aggressive B-cell leukemia. Thus, repetitive MuLV-related ERV sequences can participate in aberrant end-joining events that promote development of aggressive B-cell leukemia.

BCG Vaccine Protection Against Mycobacterium tuberculosis Infection by Level of Exposure in The Gambia.

In Indonesia, BCG vaccine protection against Mycobacterium tuberculosis infection decreased with increasing exposure to the pathogen. We aimed to validate these findings in Africa. Poisson regression was used to estimate BCG protection, stratified by pathogen exposure using an exposure score, against enzyme-linked immunospot assay conversion at 3 months in 220 Gambian case contacts. Although the interaction between BCG and exposure was not significant (P = .13), BCG protection was strongest in the lowest-exposure tertile (relative risk, 0.35 [95% confidence interval, .15-.82; P = .02] vs 0.50 [.30-.83; P = .008] and 0.71 (.45-1.13; P = .1] for the middle and highest-exposure tertiles, respectively. These results are consistent with those from Indonesia.

Reliability of a smartphone application to measure physical activity.

The aim of this study was to evaluate how accurate is a smartphone app to measure a physical activity parameter (steps). Physical Education undergraduate students (n = 46), both male and female, were recruited. A tally counter, a validated device (Xiaomi Mi Band 2®) and My Active Life app were used to perform the steps count. Each participant took three low-intensity treadmill walks (5 km h-1), with a number of target steps (500-, 1000- and 1500-steps walk). Visual agreement analyses was performed through Bland-Altman plots. There was no significant interaction between steps walks and device during treadmill walking test (F(2,84) = 3.854; p = 0.07). Differences in steps measured by Mi Band were not different from 0 in 500-steps walk (p = 0.243) and 1000-steps walk (p = 0.350), and in My Active Life in 500-steps walk (p = 0.177) and 1500-steps walk (p = 0.221). Bland-Altman analyses indicated an acceptable agreement between My active Life app and Mi Band devices for 1000-steps walk (-359.01; 310.43) and 1500-steps walk (-572.97; 377.11). In conclusion, My Active Life app showed accuracy in measuring total steps, in longer walking activities (e.g. higher than 1000 steps), and can be used on a daily basis and in research setting.

Association between physical activity and subjective memory decline triggered by the COVID-19 pandemic: Findings from the PAMPA cohort.

Implementation of social distancing reduced the incidence of coronavirus disease (COVID-19) cases. Nevertheless, this strategy has other undesirable effects such as physical inactivity and psychological distress, which are associated with cognitive impairment. We aimed to examine whether physical activity during social distancing restrictions could reduce the risk of subjective memory decline in adults. Participants (n=2321) completed the baseline assessment of PAMPA cohort (Prospective Study About Mental and Physical Health), a ambispective cohort study conducted in southern Brazil. An online-based, self-administered questionnaire assessed physical activity and self-rated memory in two different periods: before and during social distancing. Data collection was executed from June 22nd to July 23rd 2020. Adjusted Poisson regression models were performed and values reported in prevalence ratio (PR) with 95% confidence interval (CI). Participants presented with a mean age of 38.2 (95%CI: 37.5, 38.9) years. Most were women (76.6%), had at least a university degree (66.7%), and were overweight or obese (53.3%). Subjective memory decline was reported by 30.0% (95%CI: 27.7%, 32.4%) of respondents. Most individuals with subjective memory decline reported being physically inactive during the pandemic of COVID-19. Participants were less likely to experience subjective memory decline if they either became (PR: 0.56; 95%CI: 0.36, 0.89) or remained (PR: 0.68; 95%CI: 0.49, 0.93) physically active compared to inactive respondents. Physical activity participation during social distancing reduced the likelihood of subjective memory decline in adults. Physical activity should be highlighted as a potential alternative to reduce the burden of the COVID-19 pandemic on cognitive function and mental health.

Multimorbidity and leisure-time physical activity over the life course: a population-based birth cohort study.

BACKGROUND: We aimed to test which life course model best described the association between leisure-time physical activity (LTPA) and multimorbidity at age 55. We analyzed data from birth to age 55 using the database from the 1958 National Child Development Survey. METHODS: Multimorbidity was considered as the presence of more than one chronic condition. LTPA was measured through questionnaires from 1965 (age 7) to 2013 (age 55), which were applied in eight different occasions. We compared the fit of a series of nested adjusted logistic regression models (representing either the critical, accumulation or sensitive period models) with a fully saturated model. Data were reported as odds ratio (OR) and 95% confidence interval (CI). RESULTS: From an eligible sample of 15,613 cohort members, 9137 were interviewed in the latest sweep (58.5%). Men were more physically active than women at ages 11, 16, and 23 (p < 0.001). LTPA every day in the week was more frequent in women than men in ages 33, 42, and 50 (p < 0.001). The prevalence of multimorbidity at age 55 was 33.0% (n = 2778). The sensitive analysis revealed that LTPA during adolescence (OR: 0.83; 95% CI: 0.70, 0.98) and mid adult life (age 50 and 55; OR: 0.82; 95%CI: 0.69, 0.98) have a stronger effect on the risk for multimorbidity at age 55 considering all other life stages in the model. Also, adolescence showed a critical independent effect on the risk for multimorbidity (OR: 0.82; 95%CI: 0.70, 0.97). No difference was found between those models. CONCLUSIONS: These data support the notion of a protective physical activity "legacy" at early ages of childhood against multimorbidity at older ages. We highlight the need for LTPA promotion through intervention tailored especially on schooling and older ages in order to reduce the burden of multimorbidity.

A COMPARISON OF A SINGLE-DART VERSUS STAGED TWO-DART ANESTHESIA INDUCTION PROTOCOL IN PRZEWALSKI'S HORSES (EQUUS FERUS PRZEWALSKII).

Przewalski's horses (Equus ferus przewalskii) are an endangered equid species. Anesthesia administered by remote delivery is often needed to provide medical care. Behavioral and physiologic parameters were prospectively compared in 14 horses (8 females and 6 males, 3-18 yr) after a single-dart or staged two-dart anesthesia induction protocol with intramuscular medetomidine (0.06 mg/kg), butorphanol (0.05 mg/kg), thiafentanil (0.02 mg/kg), and ketamine (1 mg/kg). Seven horses were randomly assigned to receive all drugs in a single dart, and the other seven to receive medetomidine and butorphanol 10 min prior to thiafentanil and ketamine in a second dart. Induction and recovery quality were scored on a scale from 1 to 5 (worst to best), and video recordings were assessed for frequency of specific behaviors. Need for supplemental propofol was recorded. Median induction score was significantly better (P = 0.01) after two darts (4/5) compared to a single dart (3/5). Degree of muscle fasciculation (undesirable) during induction was significantly lower (P= 0.006) with the two-dart protocol. During the transition to recumbency, 71% versus 14% of horses transitioned headfirst (undesirable) after a single dart versus two darts, respectively (P= 0.07). Supplemental propofol administration was necessary in 43% of horses after two darts and in 100% of horses after a single dart (P= 0.10) to facilitate intubation and reach a working depth of anesthesia. Physiologic and recovery parameters were not significantly different between groups. Improved induction quality was observed clinically using a staged two-dart versus a single-dart protocol and should be considered when anesthetizing captive Przewalski's horses using this drug combination.

How has COVID-19 social distancing impacted physical activity patterns? Data from the PAMPA cohort, Brazil.

OBJECTIVE: This study aimed to evaluate how social distancing measures affected physical activity (PA) patterns in adults from Rio Grande do Sul, Brazil. METHODS: Participants were recruited from social and local media campaigns, contacts with private and public universities, as well as research personal contacts across the state. PA was assessed before (retrospectively) and during social distancing. Frequency (days per week) and time (minutes per day) were asked to those participants who practiced PA. Two PA variables were built to each time-frame (before and during social distancing): 1) any PA (yes/no question), and 2) sufficient PA (based on the 150 min/week cut-off point). RESULTS: Overall, 2321 participants answered the questionnaire. Any and sufficient PA decreased from before to during social distancing (22.3% and 17.0%, respectively). A linear increase of activity during social distancing was observed in participants who practiced up to 400 min or less of PA per week before social distancing. Regarding associated factors, female, overweight/obese and diagnosed chronic disease participants were less likely to practice any or sufficient PA during social distancing when compared to the period before. CONCLUSION: PA practice (both any and sufficient) decreased in Southern Brazil in the first months of social distancing. Women, overweight/obese and chronic diseased participants showed a higher decrease in PA compared to other groups. Finally, those participants who practiced PA before social distancing were more likely to continue practicing during COVID-19 pandemic.