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Inclusion at academic events is facing increased scrutiny as the communities these events serve raise their expectations for who can practically attend. Active efforts in recent years to bring more diversity to academic events have brought progress and created momentum. However, we must reflect on these efforts and determine which underrepresented groups are being disadvantaged. Inclusion at academic events is important to ensure diversity of discourse and opinion, to help build networks, and to avoid academic siloing. All of these contribute to the development of a robust and resilient academic field. We have developed these Ten Simple Rules both to amplify the voices that have been speaking out and to celebrate the progress of many Equity, Diversity, and Inclusivity practices that continue to drive the organisation of academic events. The Rules aim to raise awareness as well as provide actionable suggestions and tools to support these initiatives further. This aims to support academic organisations such as the Deep Learning Indaba, Neuromatch Academy, the IBRO-Simons Computational Neuroscience Imbizo, Biodiversity Information Standards (TDWG), Arabs in Neuroscience, FAIRPoints, and OLS (formerly Open Life Science). This article is a call to action for organisers to reevaluate the impact and reach of their inclusive practices.
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Congenital myasthenic syndromes (CMS) are a rare group of inherited disorders caused by gene defects associated with the neuromuscular junction and potentially treatable with commonly available medications such as acetylcholinesterase inhibitors and ß2 adrenergic receptor agonists. In this study, we identified and genetically characterized the largest cohort of CMS patients from India to date. Genetic testing of clinically suspected patients evaluated in a South Indian hospital during the period 2014-19 was carried out by standard diagnostic gene panel testing or using a two-step method that included hotspot screening followed by whole-exome sequencing. In total, 156 genetically diagnosed patients (141 families) were characterized and the mutational spectrum and genotype-phenotype correlation described. Overall, 87 males and 69 females were evaluated, with the age of onset ranging from congenital to fourth decade (mean 6.6 ± 9.8 years). The mean age at diagnosis was 19 ± 12.8 (1-56 years), with a mean diagnostic delay of 12.5 ± 9.9 (0-49 years). Disease-causing variants in 17 CMS-associated genes were identified in 132 families (93.6%), while in nine families (6.4%), variants in genes not associated with CMS were found. Overall, postsynaptic defects were most common (62.4%), followed by glycosylation defects (21.3%), synaptic basal lamina genes (4.3%) and presynaptic defects (2.8%). Other genes found to cause neuromuscular junction defects (DES, TEFM) in our cohort accounted for 2.8%. Among the individual CMS genes, the most commonly affected gene was CHRNE (39.4%), followed by DOK7 (14.4%), DPAGT1 (9.8%), GFPT1 (7.6%), MUSK (6.1%), GMPPB (5.3%) and COLQ (4.5%). We identified 22 recurrent variants in this study, out of which eight were found to be geographically specific to the Indian subcontinent. Apart from the known common CHRNE variants p.E443Kfs*64 (11.4%) and DOK7 p.A378Sfs*30 (9.3%), we identified seven novel recurrent variants specific to this cohort, including DPAGT1 p.T380I and DES c.1023+5G>A, for which founder haplotypes are suspected. This study highlights the geographic differences in the frequencies of various causative CMS genes and underlines the increasing significance of glycosylation genes (DPAGT1, GFPT1 and GMPPB) as a cause of neuromuscular junction defects. Myopathy and muscular dystrophy genes such as GMPPB and DES, presenting as gradually progressive limb girdle CMS, expand the phenotypic spectrum. The novel genes MACF1 and TEFM identified in this cohort add to the expanding list of genes with new mechanisms causing neuromuscular junction defects.
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Síndromes Miastênicas Congênitas , Masculino , Feminino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Síndromes Miastênicas Congênitas/diagnóstico , Acetilcolinesterase , Diagnóstico Tardio , Junção Neuromuscular/genética , Testes Genéticos , Mutação/genéticaRESUMO
Human metapneumovirus (HMPV) is a negative-strand RNA virus that frequently causes respiratory tract infections in infants, the elderly, and the immunocompromised. A hallmark of HMPV infection is the formation of membraneless, liquid-like replication and transcription centers in the cytosol termed inclusion bodies (IBs). The HMPV phosphoprotein (P) and nucleoprotein (N) are the minimal viral proteins necessary to form IB-like structures, and both proteins are required for the viral polymerase to synthesize RNA during infection. HMPV P is a homotetramer with regions of intrinsic disorder and has several known and predicted phosphorylation sites of unknown function. In this study, we found that the P C-terminal intrinsically disordered domain (CTD) must be present to facilitate IB formation with HMPV N, while either the N-terminal intrinsically disordered domain or the central oligomerization domain was dispensable. Alanine substitution at a single tyrosine residue within the CTD abrogated IB formation and reduced coimmunoprecipitation with HMPV N. Mutations to C-terminal phosphorylation sites revealed a potential role for phosphorylation in regulating RNA synthesis and P binding partners within IBs. Phosphorylation mutations which reduced RNA synthesis in a reporter assay produced comparable results in a recombinant viral rescue system, measured as an inability to produce infectious viral particles with genomes containing these single P mutations. This work highlights the critical role HMPV P plays in facilitating a key step of the viral life cycle and reveals the potential role for phosphorylation in regulating the function of this significant viral protein. IMPORTANCE Human metapneumovirus (HMPV) infects global populations, with severe respiratory tract infections occurring in infants, the elderly, and the immunocompromised. There are currently no FDA-approved therapeutics available to prevent or treat HMPV infection. Therefore, understanding how HMPV replicates is vital for the identification of novel targets for therapeutic development. During HMPV infection, viral RNA synthesis proteins localize to membraneless structures called inclusion bodies (IBs), which are sites of genome replication and transcription. The HMPV phosphoprotein (P) is necessary for IBs to form and for the virus to synthesize RNA, but it is not known how this protein contributes to IB formation or if it is capable of regulating viral replication. We show that the C-terminal domain of P is the location of a molecular interaction driving IB formation and contains potential phosphorylation sites where amino acid charge regulates the function of the viral polymerase complex.
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Metapneumovirus , Infecções por Paramyxoviridae , Idoso , Humanos , Linhagem Celular , Metapneumovirus/fisiologia , Nucleotidiltransferases , Infecções por Paramyxoviridae/virologia , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Infecções Respiratórias , RNA , Proteínas Virais/genética , Proteínas Virais/metabolismo , Compartimentos de Replicação Viral/metabolismo , Replicação Viral , Corpos de Inclusão Viral/metabolismoRESUMO
OBJECTIVE: To describe clinicians' attitudes, knowledge and practice relating to the anti-müllerian hormone (AMH) test. DESIGN: Cross-sectional nationwide survey. SETTING: Australia. POPULATION OR SAMPLE: A total of 362 general practitioners (GPs), gynaecologists and reproductive specialists. METHODS: Clinicians were recruited through relevant professional organisations, with data collected from May 2021 to April 2022. MAIN OUTCOME MEASURES: Clinicians' attitudes, knowledge and practice relating to the AMH test, measured using multiple choice, Likert scales and open-ended items. RESULTS: Fifteen percent of GPs (n = 27) and 40% of gynaecologists and other specialists (n = 73) order at least one AMH test per month. Specialists reported raising the idea of testing most of the time, whereas GPs reported that patient request was more common. Half of clinicians lacked confidence interpreting (n = 182, 51%) and explaining (n = 173, 48%) an AMH result to their patients. Five percent (n = 19) believed the test was moderately/very useful in predicting natural conception/birth and 22% (n = 82) believed the same for predicting premature menopause, despite evidence that the test cannot reliably predict either. Forty percent (n = 144) had previously ordered the test to help with reproductive planning and 21% (n = 75) to provide reassurance about fertility. CONCLUSIONS: Clinicians reported use of AMH testing in clinical circumstances not supported by the evidence. With the proliferation of direct-to-consumer testing, efforts to support clinicians in the judicious use of testing and effectively navigating patient requests are needed.
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Hormônio Antimülleriano , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Hormônio Antimülleriano/sangue , Estudos Transversais , Feminino , Austrália , Adulto , Masculino , Padrões de Prática Médica/estatística & dados numéricos , Atitude do Pessoal de Saúde , Clínicos Gerais , Ginecologia , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
INTRODUCTION AND HYPOTHESIS: There is a paucity of evidence on the healthcare preferences of active female young adults with urinary incontinence (UI). This research is aimed at examining the population's healthcare preferences and priorities and their characteristics and experiences to improve access to and use of services. METHODS: This cross-sectional online survey study used a convenience community sample. Participants resided in Australia, were 18-30 years old, had self-reported engagement in physical activity of any frequency and self-reported urine leakage in the previous 4 weeks and met other eligibility criteria. Data were analysed using descriptive analyses. RESULTS: Thirty-nine participants took part in the study. The majority engaged in recreational exercise (74.2%) and experienced UI of slight to moderate severity (82.9%). Participants preferred to access information and support anonymously online (71.4%) from general practitioners (58.8%), medical specialists (50.0%) or physiotherapists (44.1%). All participants wanted to be involved in the UI management decision-making process. Participants prioritised knowing information over cost (38.2%), changes to daily habits (35.3%) and potential risks or side effects (23.5%) when making decisions about management of UI. CONCLUSION: The results highlight the diversity among active female young adults with UI. They emphasise the need for shared decision making and highlight key information needs, providing the basis for the development of decision-making tools and protocols specific to this population. They demonstrate the need for anonymous online information and support, and draw attention to the presence of UI among young recreational exercisers, highlighting the importance of ensuring that information and support is available within this demographic.
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Preferência do Paciente , Incontinência Urinária , Humanos , Feminino , Adulto , Estudos Transversais , Incontinência Urinária/terapia , Adulto Jovem , Adolescente , Preferência do Paciente/estatística & dados numéricos , Austrália , Inquéritos e Questionários , Exercício FísicoRESUMO
INTRODUCTION: The role of social support in antiretroviral therapy (ART) uptake and retention among pregnant and postpartum women in Ghana's capital, Accra, has received limited attention in the literature. This cross-sectional study extends existing knowledge by investigating the role of social support in ART adherence and retention among pregnant and postpartum women in Accra. METHODS: We implemented a cross-sectional study in eleven (11) public health facilities. Convenience sampling approach was used to recruit 180 participants, out of which 176 with completed data were included in the study. ART adherence in the three months preceding the survey (termed consistent uptake), and ART retention were the outcomes of interest. Initial analysis included descriptive statistics characterized by frequencies and percentages to describe the study population. In model building, we included all variables that had p-values of 0.2 or lesser in the bivariate analysis to minimize negative confounding. Overall, a two-sided p-value of < 0.05 was considered statistically significant. Data were analyzed using Stata version 14.1 (College Station, TX). RESULTS: In the multivariate model, we realized a lower odds trend between social support score and consistent ART adherence, however, this was insignificant. Similarly, both the univariate and multivariate models showed that social support has no relationship with ART retention. Meanwhile, urban residents had a higher prevalence of ART adherence (adjusted Prevalence ratio (aPR) = 2.04, CI = 1.12-3.73) relative to rural/peri-urban residents. As compared to those below age 30, women aged 30-34 (aPR = 0.58, CI = 0.34-0.98) and above 35 (aPR = 0.48, CI = 0.31-0.72) had lower prevalence of ART adherence Women who knew their partner's HIV status had lower prevalence of ART adherence compared to those who did not know (aPR = 0.62, CI = 0.43-0.91). Also, having a rival or co-wife was significantly associated with ART retention such that higher prevalence of ART adherence among women with rivals relative to those without rivals (aOR = 1.98, CI = 1.16-3.36). CONCLUSION: Our study showed that social support does not play any essential role in ART adherence among the surveyed pregnant and postpartum women. Meanwhile, factors such as having a rival and being under the age of thirty play an instrumental role. The study has signaled the need for ART retention scale-up interventions to have a multi-pronged approach in order to identify the multitude of underlying factors, beyond social support, that enhance/impede efforts to achieve higher uptake and retention rates.
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Fármacos Anti-HIV , Infecções por HIV , Complicações Infecciosas na Gravidez , Gravidez , Feminino , Humanos , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Transversais , Gana/epidemiologia , Adesão à Medicação , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Período Pós-Parto , Inquéritos e Questionários , Apoio Social , Fármacos Anti-HIV/uso terapêuticoRESUMO
Reddit has provided rich data on mental health discourse. The present study uses 40,335 online posts from Reddit communities to investigate how language can contribute to the understanding of PTSD and C-PTSD. The results showed distinct language patterns in the use of first-person pronouns, cognitive processing, and emotion words, suggesting that they are separate disorders with different effects on survivors. Further, while some social media studies have differentiated submissions and comments, few have investigated the language changes between these contexts. Post-hoc results showed a clear distinction between two contexts across several linguistic markers. Discussion and future directions are explored.
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Phenomenon: Pharmacology is a fundamental healthcare discipline, but it can be difficult and counterintuitive for learners to learn. Navigation toward understanding pharmacology can be troublesome, but once the threshold to comprehension is crossed, learners can experience a transformative shift in their ways of thinking and practicing. We conducted an in-depth examination of threshold concepts within pharmacology, aiming to identify and prioritize their learning to improve the medical curriculum and enhance medical treatment and patient safety. Approach: We carried out a consensus generation process using the Nominal Group Technique (NGT) to identify potential threshold concepts in pharmacology. Participant groups of pharmacology experts and medical students considered, identified, reviewed, and ranked potential pharmacology threshold concepts within their own group. Then, using a logical, step-by-step approach, we combined the final ranked data from these multiple NGT sessions. We further analyzed these data using an abductive analysis approach; data were coded, categorized, reorganized, and conceptually mapped after critical evaluation. Conceptual themes were established corresponding to different phases of cognitive schema development. Findings: Six comprehensive conceptual themes were identified: Drug Mechanism of Action; Pharmacotherapeutics; Pharmacokinetics; Drug Receptor Interactions; Drug Terminology and Nomenclature; and Signaling Pathways. These concepts align with many of the key attributes of threshold concepts (e.g., troublesome, integrative and transformative). The cognitive schematic themes generated were (i) acquisition-troublesome; (ii) acquisition-transformative; (iii) automation-troublesome; (iv) automation-transformative. Insights: Transformative learning involves different stages of cognitive schema evolution, including acquisition, elaboration, and automation, and is influenced by both the inherent challenges of the concepts and limitations of human cognition. The high interactivity of these troublesome concepts challenge schema acquisition and automation. Troublesome concepts underpinning procedures or skills, while not easily explained by cognitive rules, can lead to slow, awkward, error-prone performance, creating additional barriers for practice. Integrating concepts into a coherent structure leads to the irreversible assimilation of knowledge and the transferability of both knowledge and skills, influencing learners' epistemological transitions and ontological transformations at theoretical and professional levels. Further work on designing instructional models around assisting and automating schemas around identified troublesome knowledge, while addressing the impact of cognitive load, has the potential to promote transformational learning.
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BACKGROUND: Good Samaritan Laws are a harm reduction policy intended to facilitate a reduction in fatal opioid overdoses by enabling bystanders, first responders, and health care providers to assist individuals experiencing an overdose without facing civil or criminal liability. However, Good Samaritan Laws may not be reaching their full impact in many communities due to a lack of knowledge of protections under these laws, distrust in law enforcement, and fear of legal consequences among potential bystanders. The purpose of this study was to develop a systems-level understanding of the factors influencing bystander responses to opioid overdose in the context of Connecticut's Good Samaritan Laws and identify high-leverage policies for improving opioid-related outcomes and implementation of these laws in Connecticut (CT). METHODS: We conducted six group model building (GMB) workshops that engaged a diverse set of participants with medical and community expertise and lived bystander experience. Through an iterative, stakeholder-engaged process, we developed, refined, and validated a qualitative system dynamics (SD) model in the form of a causal loop diagram (CLD). RESULTS: Our resulting qualitative SD model captures our GMB participants' collective understanding of the dynamics driving bystander behavior and other factors influencing the effectiveness of Good Samaritan Laws in the state of CT. In this model, we identified seven balancing (B) and eight reinforcing (R) feedback loops within four narrative domains: Narrative 1 - Overdose, Calling 911, and First Responder Burnout; Narrative 2 - Naloxone Use, Acceptability, and Linking Patients to Services; Narrative 3 - Drug Arrests, Belief in Good Samaritan Laws, and Community Trust in Police; and Narrative 4 - Bystander Naloxone Use, Community Participation in Harm Reduction, and Cultural Change Towards Carrying Naloxone. CONCLUSIONS: Our qualitative SD model brings a nuanced systems perspective to the literature on bystander behavior in the context of Good Samaritan Laws. Our model, grounded in local knowledge and experience, shows how the hypothesized non-linear interdependencies of the social, structural, and policy determinants of bystander behavior collectively form endogenous feedback loops that can be leveraged to design policies to advance and sustain systems change.
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Redução do Dano , Overdose de Opiáceos , Humanos , Connecticut , Overdose de Opiáceos/prevenção & controle , Antagonistas de Entorpecentes/uso terapêutico , Naloxona/uso terapêutico , Overdose de Drogas/prevenção & controle , Política de Saúde/legislação & jurisprudência , Aplicação da LeiRESUMO
BACKGROUND: Wedge osteotomies are ubiquitous in pediatric orthopaedics and limb deformity surgery; however, there is no universally preferred methodology for these procedures. This study aims to determine the relative accuracy and effectiveness of several measuring and marking methods to guide best practices for wedge-shaped osteotomies in long bones. METHODS: An observational cohort study was completed. Orthopaedic residents (postgraduate years 1 to 5) completed 30-degree wedge osteotomies on a sawbone (Pacific Research Lab) femur utilizing a standard oscillating saw under 3 measuring conditions: (1) no measurement tool, (2) 30-degree triangle, and (3) goniometer, in combination with 2 different marking methods: (1) marking pen or (2) pin placement. Demographic characteristics and osteotomy performance (quality, completion time, and accuracy) were assessed. Quality was ranked as perfect (1), mild step-off (2), or gross surface irregularity (3). Multivariate regressions and analysis of variance were performed comparing demographics, osteotomy performance, and measuring methods. RESULTS: Twenty-four residents were included for analysis; 6 were female (25%). Female sex was independently associated with longer completion time when evaluating all combined scenarios (138 vs. 99 s, P =0.003) without differences in surface quality or angle accuracy. There were no significant associations between measuring technique and accuracy or surface quality, but use of the goniometer and the triangle both were associated with significantly longer completion time compared with no visual aid ( P =0.002 and 0.007). When controlling for measuring technique, use of the pen as a marking technique had significantly shorter completion times ( P <0.001), higher surface quality ( P <0.001), and better accuracy ( P <0.001) than guide pins. CONCLUSIONS: We recommend the use of a marking pen in combination with the surgeon's preferred measuring guide to optimize trainees' performance of closing wedge osteotomies. Future research is necessary to corroborate these findings in a higher fidelity setting, such as a cadaveric study. Further, while male residents complete wedge osteotomies quicker than female residents, quality and accuracy are comparable among trainees. Slower pace should not be conflated with poor performance but rather should inform effective intraoperative teaching for diverse trainees.
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Fêmur , Osteotomia , Criança , Humanos , Masculino , Feminino , Fêmur/cirurgia , Osteotomia/métodos , Fixadores Internos , Extremidade InferiorRESUMO
BACKGROUND: One in 4 children with cerebral palsy (CP) will undergo orthopaedic surgery during their childhood. Despite its ubiquity, postoperative pain control has been poorly studied in this patient population. Moreover, poor pain management has been associated with adverse surgical outcomes. Multimodal analgesic injections have been well studied in the adult population, demonstrating safety and efficacy in reducing postoperative pain and narcotic consumption, but this modality has not been studied in pediatric patients undergoing similarly complex procedures. The objective of this study was to evaluate the efficacy of a multimodal surgical site injection for postoperative pain control following operative management of hip dysplasia in patients with CP. METHODS: After obtaining IRB approval, a multicenter, randomized double-blind placebo control trial was completed. Patients below 18 years old with a diagnosis of CP who were scheduled for varus derotation osteotomy (VDRO) of the proximal femur were randomized to receive a surgical-site injection with either a combination of ropivacaine (3 mg/kg), epinephrine (0.5 mg), and ketorolac (0.5 mg/kg) (experimental group) or normal saline (control). All included patients had identical postoperative care, including immobilization, physical therapy, and standardized, multimodal postoperative pain control. Pain scores and narcotic consumption were recorded at regular intervals and compared between groups utilizing two-tailed t test or a nonparametric Mann-Whitney test for quantitative variables and a Fischer exact test for categorical variables. RESULTS: Thirty-four patients were included, evenly divided between study arms. There were no significant differences in demographic variables, gross motor function classification system (GMFCS), comorbidities, preoperative radiographic parameters, or concomitant surgeries between groups. Patients in the experimental group required significantly lower narcotic medications at all postoperative time points from PACU until hospital discharge compared with controls (0.41 ± 0.42 vs. 1.87 ± 2.05 total morphine mEQ/kg, P=0.01). Similarly, patients in the experimental group were found to have significantly lower pain scores throughout their hospital stays compared with controls (1.0 ± 0.6 vs. 2.4 ± 1.1 mean pain score, P<0.001). There were no significant differences in operative time, OR time, blood transfusion requirements or hospital length of stay between groups. There were no adverse medication reactions or injection site complications in either group. CONCLUSIONS: In patients with CP undergoing hip reconstruction, surgical-site injection with a multimodal analgesic combination improves pain control and reduces narcotic consumption in the early postoperative period with no observed adverse effects. SIGNIFICANCE: Local multimodal analgesic injections should be adopted as part of standard multimodal pain control in this patient population for all osseous surgeries. LEVEL OF EVIDENCE: Level I-therapeutic.
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PURPOSE: To apply principles of group model building (GMB), a participatory systems science approach, to identify barriers and opportunities for collective impact around nutrition programming to reduce cancer risk for immigrant communities in an urban environment. METHODS: We convened four in-person workshops applying GMB with nine community partners to generate causal loop diagrams (CLDs)-a visual representation of hypothesized causal relationships between variables and feedback structures within a system. GMB workshops prompted participants to collaboratively identify programmatic goals and challenges related to (1) community gardening, (2) nutrition education, (3) food assistance programs, and (4) community-supported agriculture. Participants then attended a plenary session to integrate findings from all workshops and identify cross-cutting ideas for collective action. RESULTS: Several multilevel barriers to nutrition programming emerged: (1) food policies center the diets and practices of White Americans and inhibit culturally tailored food guidelines and funding for culturally appropriate nutrition education; (2) the lack of culturally tailored nutrition education in communities is a missed opportunity for fostering pride in immigrant food culture and sustainment of traditional food practices; and (3) the limited availability of traditional ethnic produce in food assistance programs serving historically marginalized immigrant communities increases food waste and worsens food insecurity. CONCLUSION: Emergent themes coalesced around the need to embed cultural tailoring into all levels of the food system, while also considering other characteristics of communities being reached (e.g., language needs). These efforts require coordinated actions related to food policy and advocacy, to better institutionalize these practices within the nutrition space.
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Alimentos , Eliminação de Resíduos , Humanos , Estado Nutricional , Dieta , Política NutricionalRESUMO
STUDY QUESTION: What is the anti-Mullerian hormone (AMH) test usage, awareness, and perceived reasons for testing in a representative community sample of women in Australia? SUMMARY ANSWER: : Among women aged 18-55 years, 13% had heard about AMH testing and 7% had had an AMH test, with the top three reasons for testing including due to infertility investigations (51%), considering pregnancy and wanting to understand their chances (19%) or to find out if a medical condition had affected fertility (11%). WHAT IS KNOWN ALREADY: The growing availability of direct-to-consumer AMH testing has raised concerns about overuse, however as most AMH tests are paid for privately by consumers, data on test usage is not publicly available. STUDY DESIGN, SIZE, DURATION: National cross-sectional survey of 1773 women, conducted in January 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: Females aged 18-55 years were recruited from the representative 'Life in Australia' probability-based population panel and completed the survey online or by telephone. Main outcome measures included if and how participants had heard about AMH testing, whether they had ever had an AMH test, main reason for testing and test access. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 2423 women who were invited 1773 responded (73% response rate). Of these, 229 (13%) had heard about AMH testing and 124 (7%) had had an AMH test. Testing rates were highest among those currently aged 35-39 years (14%) and associated with educational attainment. Almost all accessed the test through their general practitioner or fertility specialist. Reasons for testing were: part of an infertility investigation (51%), considering pregnancy and wanting to understand chances of conceiving (19%), finding out if a medical condition had affected fertility (11%), curiosity (9%), considering egg freezing (5%), and considering delaying pregnancy (2%). LIMITATIONS, REASONS FOR CAUTION: Although the sample was large and mostly representative, it was over-represented by people holding a university degree and under-represented by people aged 18-24, however, we used weighted data where possible to account for this. All data were self-reported so there is a risk of recall bias. The number of survey items was also restricted, so the type of counselling women received prior to testing, reasons for declining an AMH test or test timing were not measured. WIDER IMPLICATIONS OF THE FINDINGS: Whilst most women reported having an AMH test for appropriate reasons, about one third had it for reasons not supported by evidence. Public and clinician education about the lack of utility of AMH testing for women not undergoing infertility treatment is needed. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by a National Health and Medical Research Council (NHMRC) Centre for Research Excellence grant (1104136) and Program grant (1113532). T.C. is supported by an NHMRC Emerging Leader Research Fellowship (2009419). B.W.M. reports research funding, consultancy and travel support from Merck. D.L. is the Medical Director of City Fertility NSW and reports consultancy for Organon, Ferring, Besins and Merck. The authors have no other competing interests. TRIAL REGISTRATION NUMBER: N/A.
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Hormônio Antimülleriano , Infertilidade , Gravidez , Humanos , Feminino , Estudos Transversais , Fertilidade , ProbabilidadeRESUMO
Live virus vaccine (LVV) purification, employing chromatography, can be challenged by low binding capacities and elution yields. Alternatively, processes relying solely on enzymatic digestion steps and size-based membrane separations can be limited by suboptimal reduction of process related impurities and poorly scalable unit operations. Here, we demonstrate that the combination of flowthrough mode chromatography and an ultrafiltration/diafiltration (UF/DF) unit operation delivers a purification process for two different LVV candidates, V590 and Measles, expressed in adherent Vero cells. For V590, chromatography with mixed mode cation exchange resins returned final product yields of â¼50% and logarithmic reduction values (LRVs) of 1.7->3.4 and 2.5-3.0 for host cell DNA (hcDNA) and host cell proteins (HCPs), respectively. For Measles, chromatography with mixed mode anion exchange resins returned final product yields of â¼50% and LRVs of 1.6 and 2.2 for hcDNA and HCPs, respectively. For both V590 and Measles processing, the employed resins cleared a key HCP, fibronectin, which could foul the UF/DF unit operation, and thusly enabling it to further reduce HCPs and to formulate the final LVV products. This integrated purification process utilizes the complementary action of the two unit operations and its applicability across LVVs supports its consideration for their processing.
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OBJECTIVE: Loss-of-control and overeating are common in adolescents with high body mass index (BMI). Mindfulness may affect negative affect, and both may relate to loss-of-control and overeating. Yet, there is limited understanding of these associations in adolescents' daily lives. METHODS: Forty-five adolescents (77% female; Mage = 14.4 years, SDage = 1.7 years) with high weight (92% with BMI [kg/m2 ] ≥85th percentile for age/sex) provided daily, repeated measurements of mindfulness, negative affect, loss-of-control, and overeating for ~7 days (M = 5.6 days; range = 1-13). Multilevel mixed modeling was conducted to test within-person (intraindividual) and between-person (interindividual) associations for the same-day (concurrent) and next-day (time-ordered/prospective). RESULTS: There were within-person and between-person associations of higher mindfulness with lower negative affect on the same-day and next-day. Greater between-person mindfulness related to lower odds of adolescents' loss-of-control occurrence (same-day) and conversely, more perceived control over eating (same-day and next-day). Greater within-person mindfulness related to less odds of next-day overeating. DISCUSSION: Dynamic relations exist among mindfulness, negative affect, and eating in adolescents at-risk for excess weight gain. Mindfulness may be an important element to consider in loss-of-control and overeating. Future work using momentary-data within an experimental design would help disentangle the intraindividual effects of increasing mindfulness/decreasing negative affect on disordered eating. PUBLIC SIGNIFICANCE: Loss-of-control and overeating are common in teenagers with high weight. Greater mindfulness-present-moment, non-judgmental attention-and less negative emotions may relate to healthier eating, but we do not know how these processes play out in teenagers' daily lives. Addressing this knowledge gap, the current findings showed that greater daily mindfulness, but not negative affect, related to less loss-of-control/overeating, suggesting the importance of mindfulness for eating patterns in teenagers' daily lives.
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Atenção Plena , Humanos , Adolescente , Feminino , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos , Comportamento Alimentar/psicologia , Aumento de Peso , Hiperfagia/psicologia , SobrepesoRESUMO
BACKGROUND: Poor adherence and under-utilization of antiretroviral therapy (ART) services have been major setbacks to achieving 95-95-95 policy goals in Sub-Saharan Africa. Social support and mental health challenges may serve as barriers to accessing and adhering to ART but are under-studied in low-income countries. The purpose of this study was to examine the association of interpersonal support and depression scores with adherence to ART among persons living with HIV (PLWH) in the Volta region of Ghana. METHODS: We conducted a cross-sectional survey among 181 PLWH 18 years or older who receive care at an ART clinic between November 2021 and March 2022. The questionnaire included a 6-item simplified ART adherence scale, the 20-item Center for Epidemiologic Studies Depression Scale (CES-D), and the 12-item Interpersonal Support Evaluation List-12 (ISEL-12). We first used a chi-squared or Fisher's exact test to assess the association between these and additional demographic variables with ART adherence status. We then built a stepwise multivariable logistic regression model to explain ART adherence. RESULTS: ART adherence was 34%. The threshold for depression was met by 23% of participants, but it was not significantly associated with adherence in multivariate analysis(p = 0.25). High social support was reported by 48.1%, and associated with adherence (p = 0.033, aOR = 3.45, 95% CI = 1.09-5.88). Other factors associated with adherence included in the multivariable model included not disclosing HIV status (p = 0.044, aOR = 2.17, 95% CI = 1.03-4.54) and not living in an urban area (p = 0.00037, aOR = 0.24, 95% CI = 0.11-0.52). CONCLUSION: Interpersonal support, rural residence, and not disclosing HIV status were independent predictors of adherence to ART in the study area.
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Depressão , Infecções por HIV , Humanos , Estudos Transversais , Depressão/epidemiologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Instituições de Assistência Ambulatorial , Antirretrovirais , Apoio SocialRESUMO
BACKGROUND: Whether increased BMI is associated with an increased risk of venous thromboembolism (VTE) is controversial. Despite this, BMI > 40 kg/m 2 remains a common cutoff for lower limb arthroplasty eligibility. Current United Kingdom national guidelines list obesity as a risk factor for VTE, but these are based on evidence that has largely failed to differentiate between potentially minor (distal deep vein thrombosis [DVT]), and more harmful (pulmonary embolism [PE] and proximal DVT) diagnoses. Determining the association between BMI and the risk of clinically important VTE is needed to improve the utility of national risk stratification tools. QUESTIONS/PURPOSES: (1) In patients undergoing lower limb arthroplasty, is BMI 40 kg/m 2 or higher (morbid obesity) associated with an increased risk of PE or proximal DVT within 90 days of surgery, compared with patients with BMI less than 40 kg/m 2 ? (2) What proportion of investigations ordered for PE and proximal DVT were positive in patients with morbid obesity who underwent lower limb arthroplasty compared with those with BMI less than 40 kg/m 2 ? METHODS: Data were collected retrospectively from the Northern Ireland Electronic Care Record, a national database recording patient demographics, diagnoses, encounters, and clinical correspondence. Between January 2016 and December 2020, 10,217 primary joint arthroplasties were performed. Of those, 21% (2184 joints) were excluded; 2183 were in patients with multiple arthroplasties and one had no recorded BMI. All 8033 remaining joints were eligible for inclusion, 52% of which (4184) were THAs, 44% (3494) were TKAs, and 4% (355) were unicompartmental knee arthroplasties; all patients had 90 days of follow-up. The Wells score was used to guide the investigations. Indications for CT pulmonary angiography for suspected PE included pleuritic chest pain, reduced oxygen saturations, dyspnea, or hemoptysis. Indications for ultrasound scans for suspected proximal DVT included leg swelling, pain, warmth, or erythema. Distal DVTs were recorded as negative scans because we do not treat them with modified anticoagulation. The division of categories was set at BMI 40 kg/m 2 , a common clinical cutoff used in surgical eligibility algorithms. Patients were grouped according to WHO BMI categories to assess for the following confounding variables: sex, age, American Society of Anesthesiologists grade, joint replaced, VTE prophylaxis, grade of operative surgeon, and implant cement status. RESULTS: We found no increase in the odds of PE or proximal DVT in any WHO BMI category. When comparing patients with BMI less than 40 kg/m 2 with those with a BMI of 40 kg/m 2 or higher, there was no difference in the odds of PE (0.8% [58 of 7506] versus 0.8% [four of 527]; OR 1.0 [95% CI 0.4 to 2.8]; p > 0.99) or proximal DVT (0.4% [33 of 7506] versus 0.2% [one of 527]; OR 2.3 [95% CI 0.3 to 17.0]; p = 0.72). Of those who received diagnostic imaging, 21% (59 of 276) of CT pulmonary angiograms and 4% (34 of 718) of ultrasounds were positive for patients with BMI less than 40 kg/m 2 compared with 14% (four of 29; OR 1.6 [95% CI 0.6 to 4.5]; p = 0.47) and 2% (one of 57; OR 2.7 [95% CI 0.4 to 18.6]; p = 0.51) for patients with BMI 40 kg/m 2 or higher. There was no difference in the percentage of CT pulmonary angiograms ordered (4% [276 of 7506] versus 5% [29 of 527]; OR 0.7 [95% CI 0.5 to 1.0]; p = 0.07) or ultrasounds ordered (10% [718 of 7506] versus 11% [57 of 527]; OR 0.9 [95% CI 0.7 to 1.2]; p = 0.49) for BMI less than 40 kg/m 2 and BMI 40 kg/m 2 or higher. CONCLUSION: Increased BMI should not preclude individuals from lower limb arthroplasty based on suspected risk of clinically important VTE. National VTE risk stratification tools should be based on evidence assessing clinically relevant VTE (specifically, proximal DVT, PE, or death of thromboembolism) only. LEVEL OF EVIDENCE: Level III, therapeutic study.
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BACKGROUND: Accurate and efficient diagnosis, as well as a consistent and effective treatment of acute hematogenous osteomyelitis, are paramount to ensure successful clinical outcomes. Noninvasive measures of isolating the causative pathogen from blood cultures have low sensitivity, with published rates often <50%. The use of interventional radiology (IR)-guided percutaneous biopsy has gained traction as a nonsurgical means of obtaining tissue cultures with a reported increased sensitivity of >90%. This study aims to determine the utility of IR-guided biopsy in the management of pediatric patients with acute hematogenous pediatric osteomyelitis (OM). METHODS: An IRB-approved retrospective review was completed of children younger than 18 years admitted to a single institution for treatment of magnetic resonance imaging or culture/biopsy-proven acute hematogenous OM. Patients were excluded for the diagnosis of chronic recurrent multifocal OM, incomplete documentation, treatment initiation at an outside institution, open surgical debridement, and concomitant septic arthritis. Patients who underwent IR-guided biopsy were compared with those treated empirically without biopsy. RESULTS: Fifty patients were included for analysis. Fifteen (30%) had IR-guided biopsies; 35 (70%) were treated empirically. The average age at diagnosis was 11.8 years old (SD: 4.9). Of the 15 patients who underwent IR-guided biopsy, a pathogen was identified in 12 cases (80%); 14 of these patients had concomitant blood cultures with only 1 (7%) positive result ( P <0.01). Of the 11 patients with positive IR-guided biopsy results in the setting of negative blood cultures, 9 (82%) had alterations in their antibiotic regimen as a result of the biopsy. The average time from blood sample collection to definitive antibiotic initiation was nearly double that of time from IR-guided biopsy collection to definitive antibiotic initiation (70.8 vs. 36 h; P <0.01). CONCLUSION: IR-guided biopsy increased pathogen identification by 47% over blood cultures alone and decreased the time to definitive antibiotics. As such, IR-guided biopsy is an effective and safe diagnostic tool for pathogen identification and appropriate antibiotic selection. Orthopaedic surgeons are encouraged to incorporate IR-guided biopsy early in the treatment pathway for patients with acute OM without an indication for open surgical intervention. LEVEL OF EVIDENCE: Level III; retrospective comparative study.
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Osteomielite , Radiologia Intervencionista , Humanos , Criança , Estudos Retrospectivos , Biópsia , Osteomielite/diagnóstico , Osteomielite/tratamento farmacológico , Antibacterianos/uso terapêutico , Doença AgudaRESUMO
BACKGROUND: Postoperative urinary retention (POUR) is a common surgical complication of major joint arthroplasty and is associated with increased lengths of stay and urinary tract infections. Studies have found that certain anticholinergic medications and reduced mobility are associated with POUR. This study assessed the effect of anticholinergic burden and later postoperative ambulation on POUR. METHODS: In this retrospective cohort study, we included subjects who had undergone elective primary or revision hip or knee arthroplasty (total hip arthroplasty [THA] or total knee arthroplasty [TKA]) between March 2015 and December 2017 in a single health system. Anticholinergic burden was measured using the Anticholinergic Drug Scale (ADS). We performed bivariate and multivariable logistic regression with POUR as the dependent variable. Of the 1,397 study subjects, 622 (45%) underwent THA and 775 (55%) underwent TKA. Their mean age was 65 years (range, 21 to 98), and 841 (60%) were women. POUR developed in 183 (13%) subjects. RESULTS: In multivariable analyses, ADS was associated with POUR after THA (P < .05), but not TKA (P = .08), while later ambulation was not associated with POUR after either procedure (P > .3 for both). CONCLUSION: Anticholinergic burden after THA was independently associated with POUR. Strategies to reduce anticholinergic burden may help reduce POUR after THA.
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Artroplastia de Quadril , Artroplastia do Joelho , Retenção Urinária , Humanos , Feminino , Idoso , Masculino , Retenção Urinária/induzido quimicamente , Retenção Urinária/epidemiologia , Estudos Retrospectivos , Cateterismo Urinário/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Extremidade InferiorRESUMO
Adolescent disordered eating and obesity are interrelated and adversely relate to mental and metabolic health. Parental feeding practices have been associated with adolescent disordered eating and obesity. Yet, observable interactions related to food parenting have not been well characterized. To address this gap, N = 30 adolescents (M ± SD 14 ± 2 year) at risk for adult obesity due to above-average body mass index (BMI ≥70th percentile) or parental obesity (BMI ≥30 kg/m2 ) participated in a video-recorded parent-adolescent task to discuss a food/eating-related disagreement. Interactions were coded for individual/dyadic affect/content using the Interactional Dimensions Coding System. We examined associations of interaction qualities with parent-reported food practices, adolescent disordered eating behaviors/attitudes, and insulin resistance. Reported parenting practices were correlated with multiple interaction qualities (p-values <0.05), with the most consistent correspondence between parent-reported pressure to eat (e.g., pressure to eat more healthy foods) and negative aspects of parent-adolescent interactions. Also, after accounting for adolescent age, sex, and BMI-standard score, parent-adolescent interaction qualities were associated with adolescents' disordered eating and insulin resistance. Specifically, greater adolescent problem-solving related to less adolescent global disordered eating, shape, and weight concern (p-values <0.05); adolescent autonomy related to less weight concern (p = 0.03). Better parent communication skills were associated with less adolescent eating concern (p = 0.04), and observed dyadic mutuality related to adolescents' lower insulin resistance (p = 0.03). Parent-adolescent interaction qualities during food/eating-related disagreements show associations with parent-reported food practices and adolescent disordered eating. This method may offer a tool for measuring the qualities of parent-adolescent food/eating-related interactions. A nuanced understanding of conversations about food/eating may inform family-based intervention in youth at-risk for adult obesity.