40 research outputs found
Microbial Diversity in the Eukaryotic SAR Clade: Illuminating the Darkness Between Morphology and Molecular Data
Despite their diversity and ecological importance, many areas of the SARâStramenopila, Alveolata, and Rhizariaâclade are poorly understood as the majority (90%) of SAR species lack molecular data and only 5% of species are from well-sampled families. Here, we review and summarize the state of knowledge about the three major clades of SAR, describing the diversity within each clade and identifying synapomorphies when possible. We also assess the âdark areaâ of SAR: the morphologically described species that are missing molecular data. The majority of molecular data for SAR lineages are characterized from marine samples and vertebrate hosts, highlighting the need for additional research effort in areas such as freshwater and terrestrial habitats and ânon-vertebrateâ hosts. We also describe the paucity of data on the biogeography of SAR species, and point to opportunities to illuminate diversity in this major eukaryotic clade. See also the video abstract above
Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism
Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4â22 (Îe4â22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Îe4â22â/â mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs
Pelvic and breast examination skills curricula in United States medical schools: a survey of obstetrics and gynecology clerkship directors
Background: Learning to perform pelvic and breast examinations produces anxiety for many medical students. Clerkship directors have long sought strategies to help students become comfortable with the sensitive nature of these examinations. Incorporating standardized patients, simulation and gynecologic teaching associates (GTAs) are approaches gaining widespread use. However, there is a paucity of literature guiding optimal approach and timing. Our primary objective was to survey obstetrics and gynecology (Ob/Gyn) clerkship directors regarding timing and methods for teaching and assessment of pelvic and breast examination skills in United States medical school curricula, and to assess clerkship director satisfaction with current educational strategies at their institutions. Methods: Ob/Gyn clerkship directors from all 135 Liaison Committee on Medical Education accredited allopathic United States medical schools were invited to complete an anonymous 15-item web-based questionnaire. Results: The response rate was 70%. Pelvic and breast examinations are most commonly taught during the second and third years of medical school. Pelvic examinations are primarily taught during the Ob/Gyn and Family Medicine (FM) clerkships, while breast examinations are taught during the Ob/Gyn, Surgery and FM clerkships. GTAs teach pelvic and breast examinations at 72 and 65% of schools, respectively. Over 60% of schools use some type of simulation to teach examination skills. Direct observation by Ob/Gyn faculty is used to evaluate pelvic exam skills at 87% of schools and breast exam skills at 80% of schools. Only 40% of Ob/Gyn clerkship directors rated pelvic examination training as excellent, while 18% rated breast examination training as excellent. Conclusions: Pelvic and breast examinations are most commonly taught during the Ob/Gyn clerkship using GTAs, simulation trainers and clinical patients, and are assessed by direct faculty observation during the Ob/Gyn clerkship. While the majority of Ob/Gyn clerkship directors were not highly satisfied with either pelvic or breast examination training programs, they were less likely to describe their breast examination training programs as excellent as compared to pelvic examination trainingâoverall suggesting an opportunity for improvement. The survey results will be useful in identifying future challenges in teaching such skills in a cost-effective manner. Electronic supplementary material The online version of this article (doi:10.1186/s12909-016-0835-6) contains supplementary material, which is available to authorized users
International consensus guidelines for the diagnosis and management of food proteinâinduced enterocolitis syndrome: Executive summaryâWorkgroup Report of the Adverse Reactions to Foods Committee, American Academy of Allergy, Asthma & Immunology
Food protein-induced enterocolitis (FPIES) is a non-IgE cell- mediated food allergy that can be severe and lead to shock. Despite the potential seriousness of reactions, awareness of FPIES is low; high-quality studies providing insight into the pathophysiology, diagnosis, and management are lacking; and clinical outcomes are poorly established. This consensus document is the result of work done by an international workgroup convened through the Adverse Reactions to Foods Committee of the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group. These are the first international evidence-based guidelines to improve the diagnosis and management of patients with FPIES. Research on prevalence, pathophysiology, diagnostic markers, and future treatments is necessary to improve the care of patients with FPIES. These guidelines will be updated periodically as more evidence becomes available
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Characterizing Long COVID in Children and Adolescents
ImportanceMost research to understand postacute sequelae of SARS-CoV-2 infection (PASC), or long COVID, has focused on adults, with less known about this complex condition in children. Research is needed to characterize pediatric PASC to enable studies of underlying mechanisms that will guide future treatment.ObjectiveTo identify the most common prolonged symptoms experienced by children (aged 6 to 17 years) after SARS-CoV-2 infection, how these symptoms differ by age (school-age [6-11 years] vs adolescents [12-17 years]), how they cluster into distinct phenotypes, and what symptoms in combination could be used as an empirically derived index to assist researchers to study the likely presence of PASC.Design, setting, and participantsMulticenter longitudinal observational cohort study with participants recruited from more than 60 US health care and community settings between March 2022 and December 2023, including school-age children and adolescents with and without SARS-CoV-2 infection history.ExposureSARS-CoV-2 infection.Main outcomes and measuresPASC and 89 prolonged symptoms across 9 symptom domains.ResultsA total of 898 school-age children (751 with previous SARS-CoV-2 infection [referred to as infected] and 147 without [referred to as uninfected]; mean age, 8.6 years; 49% female; 11% were Black or African American, 34% were Hispanic, Latino, or Spanish, and 60% were White) and 4469 adolescents (3109 infected and 1360 uninfected; mean age, 14.8 years; 48% female; 13% were Black or African American, 21% were Hispanic, Latino, or Spanish, and 73% were White) were included. Median time between first infection and symptom survey was 506 days for school-age children and 556 days for adolescents. In models adjusted for sex and race and ethnicity, 14 symptoms in both school-age children and adolescents were more common in those with SARS-CoV-2 infection history compared with those without infection history, with 4 additional symptoms in school-age children only and 3 in adolescents only. These symptoms affected almost every organ system. Combinations of symptoms most associated with infection history were identified to form a PASC research index for each age group; these indices correlated with poorer overall health and quality of life. The index emphasizes neurocognitive, pain, and gastrointestinal symptoms in school-age children but change or loss in smell or taste, pain, and fatigue/malaise-related symptoms in adolescents. Clustering analyses identified 4 PASC symptom phenotypes in school-age children and 3 in adolescents.Conclusions and relevanceThis study developed research indices for characterizing PASC in children and adolescents. Symptom patterns were similar but distinguishable between the 2 groups, highlighting the importance of characterizing PASC separately for these age ranges
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe
Fear of movement in children and adolescents undergoing major surgery : a psychometric evaluation of the Tampa Scale for Kinesiophobia
Background
The objective of this study was to evaluate the psychometric properties of the 17-item Tampa Scale for Kinesiophobia (TSK) in youth.
Methods
Participants were 264 children and adolescents (58.7% female, Mage = 14.1 years, SDage = 2.51) scheduled for major surgery who were assessed before surgery, while in hospital postoperatively, and at 6 and 12 months after surgery. Exploratory factor analyses (EFA) were conducted to determine the factor structure of pre-operative TSK scores. Reliability, and convergent, discriminant, and predictive validity were examined.
Results
EFA on the 17-item TSK revealed a two-factor model distinguishing the 13 positively scored items from the 4 reverse scored items, but the fit was poor. A second EFA was conducted on the 13 positively scored items (TSK-13) revealing a three-factor model: Fear of injury, bodily vulnerability, and activity avoidance. The TSK-13 showed adequate internal consistency (Ω = 0.82) and weak convergent validity. The TSK-13 was not correlated with postoperative, in-hospital physical activity (actigraphy; r (179) = â0.10, p = 0.18) and showed adequate discriminant validity, that is correlations less than 0.70, with measures of depression (r (225) = 0.41, p < 0.001) and general anxiety (r (224)=0.35, p < 0.001). Predictive validity for pain-related disability at 12 months (r (70) = 0.34, p < 0.001) was adequate.
Conclusions
The original TSK-17 does not appear to be a meaningful measure of kinesiophobia in youth after surgery possibly because of the syntactic structure of the reverse scored items. In contrast, a modified TSK-13, comprised of only the positively scored items, revealed a 3-factor structure that is reliable and demonstrates adequate convergent, discriminant, and predictive validity.
Significance
Kinesiophobia is an important construct to evaluate in the transition from acute to chronic pain among children and adolescents. The 17 item Tampa Scale for Kinesiophobia (TSK) does not show adequate validity or reliability in youth undergoing major surgery, however, the psychometric properties of a 13-item modified scale (TSK-13) are promising
Differential Risk Factor Profiles in the Prediction of General and Pain-Specific Functional Limitations 12 Months after Major Pediatric Surgery
Pediatric chronic post-surgical pain is a surgical complication associated with various levels of functional limitation. Two commonly used measures of functional limitations in youth are the Functional Disability Inventory (FDI) and the PROMIS Pediatric Pain Interference Scale (PPIS), where the former is general, and the latter, pain specific. The aim of the present study was to prospectively compare pre-surgical youth and parent risk factors for youth functional limitations, assessed by the FDI and PPIS, 12 months after major pediatric surgery. Risk factors for the FDI and PPIS were compared in 79 dyads consisting of youth (58% female, M = 14.56 years; SD = 2.31) undergoing major surgery and one of their parents. The FDI and PPIS were highly correlated prior to surgery (r = 0.698, p < 0.001) and even more so 12 months after surgery (r = 0.807, p < 0.001). Parent pre-surgical anxiety sensitivity and youth pre-surgical functional disability significantly predicted 12-month FDI (F(6,56) = 4.443, p = 0.001, Adjusted R2 = 0.25), whereas parent pre-surgical anxiety sensitivity, trait anxiety, pain anxiety, as well as youth pain-related anxiety and worry significantly predicted 12-month PPIS (F(6,45) = 4.104, p = 0.002, Adjusted R2 = 0.27). Risk factors for 12-month general and pain-specific functional limitations differ by dyad member and type. Functional limitations in youth after surgery are predicted by youth and parent factors, however the risk factors differ between the FDI and the PPIS
sj-pdf-1-jcb-10.1177_0271678X221142533 - Supplemental material for Putative neurochemical and cell type contributions to hemodynamic activity in the rodent caudate putamen
Supplemental material, sj-pdf-1-jcb-10.1177_0271678X221142533 for Putative neurochemical and cell type contributions to hemodynamic activity in the rodent caudate putamen by Brittany M Katz, Lindsay R Walton, Kaiulani M Houston, Domenic H Cerri and Yen-Yu Ian Shih in Journal of Cerebral Blood Flow & Metabolism</p