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BACKGROUND: Patients listed for solid organ transplants (LSOTP) are at high risk for severe COVID-19 outcomes. Despite national guidelines recommending COVID-19 vaccination for LSOTP, vaccine hesitancy and underuse are reported in this population; however, reasons for this finding have not been examined thoroughly. METHODS: This single-center retrospective survey analysis aimed to characterize reasons for COVID-19 vaccine hesitancy among 110 heart, liver, and kidney patients LSOTP who had not received all the recommended vaccine doses at the time of the study. Survey questions also investigated experiences with influenza vaccination. RESULTS: Fifty-four patients (49.1%) responded to the telephone survey. The most common reasons for vaccine hesitancy were perceived lack of research in vaccine development (31%), fear of vaccine-related side effects (22%), and belief that the vaccine was unnecessary (20%). Of the respondents, 35% reported changing their vaccine perception after being listed for a transplant, most commonly attributing this to a perception that the COVID-19 vaccine is not safe for transplant recipients (32%). Gender differences in hesitancy reasons were observed, with males more likely to delay vaccination until after transplantation, although this difference was not significant (P = .07). Despite these findings, 54% of all respondents reported receiving annual influenza vaccines consistently. CONCLUSION: Despite their risk, patients LSOTP show significant hesitancy toward COVID-19 vaccines owing to perceived safety and necessity issues. The results of this study can inform targeted educational efforts to address and rectify misconceptions and concerns about COVID-19 vaccination among patients LSOTP. Future studies focused on larger, more diverse cohorts are needed to expand our understanding of and address vaccination hesitancy among this vulnerable patient population.
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BACKGROUND: Asthma is the most common chronic respiratory illness among children in Australia. While childhood asthma prevalence varies by region, little is known about variations at the small geographic area level. Identifying small geographic area variations in asthma is critical for highlighting hotspots for targeted interventions. This study aimed to investigate small area-level variation, spatial clustering, and sociodemographic risk factors associated with childhood asthma prevalence in Australia. METHODS: Data on self-reported (by parent/carer) asthma prevalence in children aged 0-14 years at statistical area level 2 (SA2, small geographic area) and selected sociodemographic features were extracted from the national Australian Household and Population Census 2021. A spatial cluster analysis was used to detect hotspots (i.e., areas and their neighbours with higher asthma prevalence than the entire study area average) of asthma prevalence. We also used a spatial Bayesian Poisson model to examine the relationship between sociodemographic features and asthma prevalence. All analyses were performed at the SA2 level. RESULTS: Data were analysed from 4,621,716 children aged 0-14 years from 2,321 SA2s across the whole country. Overall, children's asthma prevalence was 6.27%, ranging from 0 to 16.5%, with significant hotspots of asthma prevalence in areas of greater socioeconomic disadvantage. Socioeconomically disadvantaged areas had significantly higher asthma prevalence than advantaged areas (prevalence ratio [PR] = 1.10, 95% credible interval [CrI] 1.06-1.14). Higher asthma prevalence was observed in areas with a higher proportion of Indigenous individuals (PR = 1.13, 95% CrI 1.10-1.17). CONCLUSIONS: We identified significant geographic variation in asthma prevalence and sociodemographic predictors associated with the variation, which may help in designing targeted asthma management strategies and considerations for service enhancement for children in socially deprived areas.
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Asma , Asma/epidemiologia , Humanos , Criança , Pré-Escolar , Adolescente , Lactente , Austrália/epidemiologia , Masculino , Prevalência , Feminino , Análise por Conglomerados , Recém-Nascido , Fatores Socioeconômicos , Análise Espacial , Fatores de Risco , Teorema de Bayes , Fatores SociodemográficosRESUMO
PURPOSE: Radiation-mediated immune suppression limits efficacy and is a barrier in cancer therapy. Radiation induces negative regulators of tumor immunity including regulatory T cells (Treg). Mechanisms underlying Treg infiltration after radiotherapy (RT) are poorly defined. Given that dendritic cells (cDC) maintain Treg we sought to identify and target cDC signaling to block Treg infiltration after radiation. EXPERIMENTAL DESIGN: Transcriptomics and high dimensional flow cytometry revealed changes in murine tumor cDC that not only mediate Treg infiltration after RT, but associate with worse survival in human cancer datasets. Antibodies perturbing a cDC-CCL22-Treg axis were tested in syngeneic murine tumors. A prototype interferon-anti-epidermal growth factor receptor fusion protein (αEGFR-IFNα) was examined to block Treg infiltration and promote a CD8+ T cell response after RT. RESULTS: Radiation expands a population of mature cDC1 enriched in immunoregulatory markers that mediates Treg infiltration via the Treg-recruiting chemokine CCL22. Blocking CCL22 or Treg depletion both enhanced RT efficacy. αEGFR-IFNα blocked cDC1 CCL22 production while simultaneously inducing an antitumor CD8+ T cell response to enhance RT efficacy in multiple EGFR-expressing murine tumor models, including following systemic administration. CONCLUSIONS: We identify a previously unappreciated cDC mechanism mediating Treg tumor infiltration after RT. Our findings suggest blocking the cDC1-CCL22-Treg axis augments RT efficacy. αEGFR-IFNα added to RT provided robust antitumor responses better than systemic free interferon administration, and may overcome clinical limitations to interferon therapy. Our findings highlight the complex behavior of cDC after RT and provide novel therapeutic strategies for overcoming RT-driven immunosuppression to improve RT efficacy.
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Faculty career advisors who guide applicants applying to obstetrics and gynecology residency programs need updated information and resources, given the constant changes and challenges to the residency application process. Initial changes included standardization of the application timeline and interview processes. More recent changes included the utilization of a standardized letter of evaluation, initiation of program signaling, second look visit guidelines, and updated sections in the Electronic Residency Application Service. Challenges in advising include the unmatched applicant and the applicant who is couples matching in the era of program signaling. Additional considerations include applying with the current status of reproductive health law restrictions and preparing for a new residency application platform. The Undergraduate Medical Education Committee of the Association of Professors of Gynecology and Obstetrics provides this updated guide of the prior 2021 resource for advisors to increase confidence in advising students, boost professional fulfillment with advising activities, and aid in satisfaction with advising resources. This guide covers the continuing challenges and future opportunities in the resident application process.
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Clerkship directors must balance the mental wellbeing of their medical students with the demanding schedule that rotations in procedural specialties such as surgery and obstetrics and gynecology require. In this paper, the Undergraduate Medical Education Committee of the Association of Professors of Obstetrics and Gynecology argues the importance of maintaining adequate clinical exposure for learners. Involving students in overnight call provides additional clinical involvement, improved relationships with the clinical team, and a better perspective on specialist lifestyle. Educators should improve the experience for students by promoting resilience and creating a welcoming learning environment. Preparing medical students for the rigorous requirements of these clerkships allows them to thrive in the learning environment while still providing a realistic preview of the clinical experiences and demands of these specialties.
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Estágio Clínico , Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Educação de Graduação em Medicina/métodos , Estudantes de Medicina/psicologia , Feminino , Obstetrícia/educação , Masculino , Cirurgia Geral/educação , Ginecologia/educação , Competência ClínicaAssuntos
Asma , Adolescente , Criança , Pré-Escolar , Humanos , Asma/epidemiologia , Asma/tratamento farmacológico , Austrália/epidemiologiaRESUMO
Vertebrate limbs start to develop as paired protrusions from the lateral plate mesoderm at specific locations of the body with forelimb buds developing anteriorly and hindlimb buds posteriorly. During the initiation process, limb progenitor cells maintain active proliferation to form protrusions and start to express Fgf10, which triggers molecular processes for outgrowth and patterning. Although both processes occur in both types of limbs, forelimbs (Tbx5), and hindlimbs (Isl1) utilize distinct transcriptional systems to trigger their development. Here, we report that Sall1 and Sall4, zinc finger transcription factor genes, regulate hindlimb initiation in mouse embryos. Compared to the 100% frequency loss of hindlimb buds in TCre; Isl1 conditional knockouts, Hoxb6Cre; Isl1 conditional knockout causes a hypomorphic phenotype with only approximately 5% of mutants lacking the hindlimb. Our previous study of SALL4 ChIP-seq showed SALL4 enrichment in an Isl1 enhancer, suggesting that SALL4 acts upstream of Isl1. Removing 1 allele of Sall4 from the hypomorphic Hoxb6Cre; Isl1 mutant background caused loss of hindlimbs, but removing both alleles caused an even higher frequency of loss of hindlimbs, suggesting a genetic interaction between Sall4 and Isl1. Furthermore, TCre-mediated conditional double knockouts of Sall1 and Sall4 displayed a loss of expression of hindlimb progenitor markers (Isl1, Pitx1, Tbx4) and failed to develop hindlimbs, demonstrating functional redundancy between Sall1 and Sall4. Our data provides genetic evidence that Sall1 and Sall4 act as master regulators of hindlimb initiation.
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Proteínas de Ligação a DNA , Regulação da Expressão Gênica no Desenvolvimento , Membro Posterior , Proteínas com Homeodomínio LIM , Fatores de Transcrição , Animais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Camundongos , Membro Posterior/embriologia , Membro Posterior/metabolismo , Proteínas com Homeodomínio LIM/genética , Proteínas com Homeodomínio LIM/metabolismo , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismo , Botões de Extremidades/metabolismo , Botões de Extremidades/embriologia , Camundongos Knockout , Embrião de Mamíferos/metabolismo , Fator 10 de Crescimento de Fibroblastos/genética , Fator 10 de Crescimento de Fibroblastos/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismoRESUMO
The trunk axial skeleton develops from paraxial mesoderm cells. Our recent study demonstrated that conditional knockout of the stem cell factor Sall4 in mice by TCre caused tail truncation and a disorganized axial skeleton posterior to the lumbar level. Based on this phenotype, we hypothesized that, in addition to the previously reported role of Sall4 in neuromesodermal progenitors, Sall4 is involved in the development of the paraxial mesoderm tissue. Analysis of gene expression and SALL4 binding suggests that Sall4 directly or indirectly regulates genes involved in presomitic mesoderm differentiation, somite formation and somite differentiation. Furthermore, ATAC-seq in TCre; Sall4 mutant posterior trunk mesoderm shows that Sall4 knockout reduces chromatin accessibility. We found that Sall4-dependent open chromatin status drives activation and repression of WNT signaling activators and repressors, respectively, to promote WNT signaling. Moreover, footprinting analysis of ATAC-seq data suggests that Sall4-dependent chromatin accessibility facilitates CTCF binding, which contributes to the repression of neural genes within the mesoderm. This study unveils multiple mechanisms by which Sall4 regulates paraxial mesoderm development by directing activation of mesodermal genes and repression of neural genes.
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Proteínas de Ligação a DNA , Regulação da Expressão Gênica no Desenvolvimento , Mesoderma , Fatores de Transcrição , Animais , Camundongos , Diferenciação Celular , Cromatina/metabolismo , Expressão Gênica , Mesoderma/metabolismo , Somitos/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Clerkship grades in obstetrics and gynecology play an increasingly important role in the competitive application process to residency programs. An analysis of clerkship grading practices has not been queried in the past 2 decades in our specialty. OBJECTIVE: This study aimed to investigate obstetrics and gynecology clerkship directors' practices and perspectives in grading. STUDY DESIGN: A 12-item electronic survey was developed and distributed to clerkship directors with active memberships in the Association of Professors of Gynecology and Obstetrics. RESULTS: A total of 174 of 236 clerkship directors responded to the survey (a response rate of 73.7%). Respondents reported various grading systems with the fewest (20/173 [11.6%]) using a 2-tiered or pass or fail system and the most (72/173 [41.6%]) using a 4-tiered system. Nearly one-third of clerkship directors (57/163 [35.0%]) used a National Board of Medical Examiners subject examination score threshold to achieve the highest grade. Approximately 45 of 151 clerkship directors (30.0%) had grading committees. Exactly half of the clerkship directors (87/174 [50.0%]) reported requiring unconscious bias training for faculty who assess students. In addition, some responded that students from groups underrepresented in medicine (50/173 [28.9%]) and introverted students (105/173 [60.7%]) received lower evaluations. Finally, 65 of 173 clerkship directors (37.6%) agreed that grades should be pass or fail. CONCLUSION: Considerable heterogeneity exists in obstetrics and gynecology clerkship directors' practices and perspectives in grading. Strategies to mitigate inequities and improve the reliability of grading include the elimination of a subject examination score threshold to achieve the highest grade and the implementation of both unconscious bias training and grading committees.
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Estágio Clínico , Ginecologia , Obstetrícia , Estudantes de Medicina , Humanos , Ginecologia/educação , Reprodutibilidade dos Testes , Avaliação Educacional , Obstetrícia/educaçãoRESUMO
BACKGROUND: Daily IGRT images show day-to-day anatomical variations in patients undergoing fractionated prostate radiotherapy. This is of particular importance in particle beam treatments. PURPOSE: To develop a digital phantom series showing variation in pelvic anatomy for evaluating treatment planning and IGRT procedures in particle radiotherapy. METHODS: A pelvic phantom series was developed from the planning MRI and kVCT (planning CT) images along with six of the daily serial MVCT images taken of a single patient treated with a full bladder on a Tomotherapy unit. The selected patient had clearly visible yet unexceptional internal anatomy variation. Prostate, urethra, bladder, rectum, bowel, bowel gas, bone and soft tissue were contoured and a single Hounsfield Unit was assigned to each region. Treatment plans developed on the kVCT for photon, proton and carbon beams were recalculated on each phantom to demonstrate a clinical application of the series. Proton plans were developed with and without robust optimization. RESULTS: Limited to axial slices with prostate, the bladder volume varied from 6 to 46 cm3, the rectal volume (excluding gas) from 22 to 52 cm3, and rectal gas volume from zero to 18 cm3. The water equivalent path length to the prostate varied by up to 1.5 cm . The variations resulted in larger changes in the RBE-weighted Dose Volume Histograms of the non-robust proton plan and the carbon plan compared to the robust proton plan, the latter similar to the photon plan. The prostate coverage (V100%) decreased by an average of 18% in the carbon plan, 16% in the non-robust proton plan, 1.8% in the robust proton plan, and 4.4% in the photon plan. The volume of rectum receiving 75% of the prescription dose (V75%) increased by an average of 3.7 cm3, 4.7 cm3, 1.9 cm3, and 0.6 cm3 in those four plans, respectively. CONCLUSIONS: The digital pelvic phantom series provides for quantitative investigation of IGRT procedures and new methods for improving accuracy in particle therapy and may be used in cross-institutional comparisons for clinical trial quality assurance.
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Neoplasias da Próstata , Terapia com Prótons , Radioterapia de Intensidade Modulada , Humanos , Masculino , Prótons , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Reto/diagnóstico por imagem , Radioterapia de Intensidade Modulada/métodos , Pelve/diagnóstico por imagem , Fracionamento da Dose de Radiação , Carbono , Dosagem Radioterapêutica , Terapia com Prótons/métodosRESUMO
Academic seminars are an important venue through which investigators in health services research (HSR) and other clinical and translational science disciplines can share their work, gather feedback, and connect with colleagues. However, the format and focus of these seminars shifted abruptly when the coronavirus disease 2019 (COVID-19) pandemic necessitated social distancing and underscored the salience of health equity. Little is known about how contemporary academic seminars are meeting the evolving needs of the HSR community. We surveyed 2021-2022 participants in a virtual HSR seminar series to understand experiences of and priorities for the seminars. We also compared results stratified by self-reported under-represented minority (URM) status. Of 45 respondents (including 26 faculty members, 8 trainees, 9 staff members, and 2 community partners), 38% self-identified as URM. Participants reported high satisfaction with seminar quality, diversity of topics, and audience participation (median ≥4 for all outcomes in Likert-scaled items where 5 = very satisfied). Knowledge acquisition, understanding of research methods, and collaboration were commonly cited as benefits of seminar attendance. Implementation science content and external collaboration were most often endorsed as priorities for future seminars. URM participants were over three times more likely than non-URM participants to cite learning about engaging community stakeholders and historically excluded populations as a benefit of seminar participation. Virtual academic seminars can be an effective modality for knowledge sharing and collaboration worth continuing after COVID-19 restrictions are lifted. Emphasizing equity, diversity, and inclusion (EDI) values in these seminars may hold potential for advancing academic departments' own EDI goals.
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COVID-19 , Ciência Translacional Biomédica , Humanos , Aprendizagem , Retroalimentação , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To examine whether gentrification exposure is associated with future hypertension and diabetes control. METHODS: Linking records from an integrated health care system to census-tract characteristics, we identified adults with hypertension and/or diabetes residing in stably low-SES census tracts in 2014 (n = 69,524). We tested associations of census tract gentrification occurring between 2015 and 2019 with participants' disease control in 2019. Secondary analyses considered the role of residential moves (possible displacement), race and ethnicity, and age. RESULTS: Gentrification exposure was associated with improved odds of hypertension control (aOR: 1.08; 95% CI: 1.00, 1.17), especially among non-Hispanic Whites and adults >65 years. Gentrification was not associated with diabetes control overall, but control improved in the Hispanic subgroup. Disease control was similar regardless of residential moves in the overall sample, but disparate associations emerged in models stratified by race and ethnicity. CONCLUSIONS: Residents of newly gentrifying neighborhoods may experience modestly improved odds of hypertension and/or diabetes control, but associations may differ across population subgroups. POLICY IMPLICATIONS: Gentrification may support-or at least not harm-cardiometabolic health for some residents. City leaders and health systems could partner with impacted communities to ensure that neighborhood development meets the goals and health needs of all residents and does not exacerbate health disparities.
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Diabetes Mellitus , Hipertensão , Adulto , Humanos , Los Angeles/epidemiologia , Segregação Residencial , Estudos Retrospectivos , Diabetes Mellitus/epidemiologia , Hipertensão/epidemiologiaRESUMO
Background: Teaching near-peers yields numerous benefits to residents. Opportunities for near-peer teaching are typically restricted to hospital settings. Little is known about the educational potential of outpatient near-peer teaching. Objective: To describe Primary Care Teaching (PC Teach), a novel outpatient near-peer teaching experience for residents in a large, urban, internal medicine residency program; characterize its feasibility and acceptability; and evaluate changes in residents' self-reported confidence in outpatient teaching and attitudes toward teaching and primary care/outpatient medicine. Methods: In 2020-2021, following a didactic workshop, 43 postgraduate year 3 (PGY-3) residents at continuity clinics assigned to PC Teach completed a series of half-day sessions acting as preceptor to interns under attending supervision. Worksheets facilitated post-session feedback for residents and interns. Eighteen PGY-3s at nonparticipating clinics, who also completed the workshop, served as controls. We assessed process measures for feasibility and acceptability and analyzed resident attitudes using pre-post surveys. Results: Participating residents completed 2 to 8 sessions each. Post-intervention scores for confidence in outpatient teaching and attitudes toward teaching were greater, relative to pre-intervention group means, for intervention residents (median pre-post changes +0.60 [IQR 0.26, 1.26] and +0.46 [-0.04, 0.46], respectively) vs controls (-0.15 [-0.48, 0.85] and -0.36 [-0.86, 0.39]; between-group differences +0.75 [P=.03] and +0.82 [P=.02]). Changes in attitudes toward primary care/outpatient medicine did not differ significantly between intervention and control groups (+0.43 [-0.07, 0.68] and 0.04 [-0.58, 0.42]; between-group difference +0.39 [P=.12]). In multivariable analyses, odds of gains in confidence in outpatient teaching remained significantly larger for intervention residents vs controls. Conclusions: Implementing PC Teach with existing resources was feasible and acceptable, with program flexibility highlighted as a strength. Resident participation was associated with greater confidence in outpatient teaching.
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Internato e Residência , Humanos , Instituições de Assistência Ambulatorial , Hospitais , Capacitação em Serviço , Atenção Primária à SaúdeRESUMO
ABSTRACT: Recognition of the spectrum of gender identities has been a recent phenomenon in the medical profession. Over the past 20 years, medical literature related to gender identity diversity has increased several-fold, yet it more commonly addresses clinical care rather than aspects related to medical education. Medical educators continue to struggle with appropriate language and inclusive approaches when discussing gender-based aspects of medical education. Reproductive health education, including obstetrics and gynecology clerkships, is particularly vulnerable to missteps and anachronisms regarding gender identity.This article aims to provide preclinical and clinical medical educators with strategies to identify and predict situations where missteps related to gender identity inclusivity may occur in their curriculum or learning environment, and to develop approaches to improve gender identity inclusivity within medical education. The authors explore 3 areas that commonly pose challenges for medical educators: inclusive language and terminology, anatomy education, and reproductive genetics and genetic counseling. They hope the tools and strategies provided here will be useful to reproductive health medical educators across specialties to enable the realization of a more inclusive learning environment in reproductive health.
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Educação Médica , Ginecologia , Obstetrícia , Humanos , Masculino , Feminino , Identidade de Gênero , AprendizagemRESUMO
The labor and delivery floor is a unique learning environment that poses challenges to teaching medical students, with a potentially detrimental effect on their evaluations of the obstetrics and gynecology clerkship. This article, from the "To the Point" series prepared by the Association of Professors of Gynecology and Obstetrics Undergraduate Medical Education Committee, offers specific suggestions for improving undergraduate medical education in obstetrics with attention to student preparation, faculty development, nonphysician staff involvement, and patient education. Optimizing the learning environment in labor and delivery would improve student experiences and perceptions of our specialty.
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Estágio Clínico , Educação de Graduação em Medicina , Ginecologia , Obstetrícia , Estudantes de Medicina , Humanos , Obstetrícia/educaçãoRESUMO
INTRODUCTION: Criteria-led discharges (CLDs) and inpatient care pathways (ICPs) aim to standardise care and improve efficiency by allowing patients to be discharged on fulfilment of discharge criteria. This narrative systematic review aims to summarise the evidence for use of CLDs and discharge criteria in ICPs for paediatric inpatients with asthma, and summarise the evidence for each discharge criterion used. METHODS: Database search using keywords was performed using Medline, Embase and PubMed for studies published until 9 June 2022. Inclusion criteria included: paediatric patients <18 years old, admitted to hospital with asthma or wheeze and use of CLD, nurse-led discharge or ICP. Reviewers screened studies, extracted data and assessed study quality using the Quality Assessment with Diverse Studies tool. Results were tabulated. Meta-analysis was not performed due to heterogeneity of study designs and outcomes. RESULTS: Database search identified 2478 studies. 17 studies met the inclusion criteria. Common discharge criteria include bronchodilator frequency, oxygen saturation and respiratory assessment. Discharge criteria definitions varied between studies. Most definitions were associated with improvements in length of stay (LOS) without increasing re-presentation or readmission. CONCLUSION: CLDs and ICPs in the care of paediatric inpatients with asthma are associated with improvements in LOS without increasing re-presentations or readmissions. Discharge criteria lack consensus and evidence base. Common criteria include bronchodilator frequency, oxygen saturations and respiratory assessment. This study was limited by a paucity of high-quality studies and exclusion of studies not published in English. Further research is necessary to identify optimal definitions for each discharge criterion.
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Asma , Alta do Paciente , Criança , Humanos , Adolescente , Pacientes Internados , Broncodilatadores/uso terapêutico , Asma/tratamento farmacológico , HospitalizaçãoRESUMO
Recent studies illustrate the importance of regulation of cellular metabolism, especially glycolysis and pathways branching from glycolysis, during vertebrate embryo development. For example, glycolysis generates cellular energy ATP. Glucose carbons are also directed to the pentose phosphate pathway, which is needed to sustain anabolic processes in the rapidly growing embryos. However, our understanding of the exact status of glycolytic metabolism as well as genes that regulate glycolytic metabolism are still incomplete. Sall4 is a zinc finger transcription factor that is highly expressed in undifferentiated cells in developing mouse embryos, such as blastocysts and the post-implantation epiblast. TCre; Sall4 conditional knockout mouse embryos exhibit various defects in the posterior part of the body, including hindlimbs. Using transcriptomics approaches, we found that many genes encoding glycolytic enzymes are upregulated in the posterior trunk, including the hindlimb-forming region, of Sall4 conditional knockout mouse embryos. In situ hybridization and qRT-PCR also confirmed upregulation of expression of several glycolytic genes in hindlimb buds. A fraction of those genes are bound by SALL4 at the promoters, gene bodies or distantly-located regions, suggesting that Sall4 directly regulates expression of several glycolytic enzyme genes in hindlimb buds. To further gain insight into the metabolic status associated with the observed changes at the transcriptional level, we performed a comprehensive analysis of metabolite levels in limb buds in wild type and Sall4 conditional knockout embryos by high-resolution mass spectrometry. We found that the levels of metabolic intermediates of glycolysis are lower, but glycolytic end-products pyruvate and lactate did not exhibit differences in Sall4 conditional knockout hindlimb buds. The increased expression of glycolytic genes would have caused accelerated glycolytic flow, resulting in low levels of intermediates. This condition may have prevented intermediates from being re-directed to other pathways, such as the pentose phosphate pathway. Indeed, the change in glycolytic metabolite levels is associated with reduced levels of ATP and metabolites of the pentose phosphate pathway. To further test whether glycolysis regulates limb patterning downstream of Sall4, we conditionally inactivated Hk2, which encodes a rate-limiting enzyme gene in glycolysis and is regulated by Sall4. The TCre; Hk2 conditional knockout hindlimb exhibited a short femur, and a lack of tibia and anterior digits in hindlimbs, which are defects similarly found in the TCre; Sall4 conditional knockout. The similarity of skeletal defects in Sall4 mutants and Hk2 mutants suggests that regulation of glycolysis plays a role in hindlimb patterning. These data suggest that Sall4 restricts glycolysis in limb buds and contributes to patterning and regulation of glucose carbon flow during development of limb buds.
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Regulação da Expressão Gênica no Desenvolvimento , Botões de Extremidades , Animais , Camundongos , Trifosfato de Adenosina/metabolismo , Glucose/metabolismo , Glicólise/genética , Botões de Extremidades/metabolismo , Camundongos KnockoutRESUMO
OBJECTIVES: To (1) describe the dispensing of asthma preventers at hospital discharge and estimate its effect on hospital readmissions, and (2) estimate the effect of community asthma preventer dispensing on readmissions for the subgroup of children who were not prescribed an asthma preventer at discharge. DESIGN: Multisite cohort study with linked administrative data. PARTICIPANTS: Children aged 3-18 years admitted with asthma to a tertiary paediatric, mixed paediatric and adult, or regional hospital between 2017 and 2018. MAIN OUTCOME MEASURE: Hospital readmission for asthma within 12 months. RESULTS: Of the 767 participants, 201 (26.2%) were newly prescribed or requested to continue with asthma preventers. Of these, only 91 (45.3%) dispensed their discharge prescription within 3 days or had an active prescription. There was no evidence for a protective effect of discharge asthma preventer dispensing on asthma hospital readmissions within 12 months (OR 1.17, 95% CI 0.69 to 1.97, p=0.57). Of the 566 children who were not prescribed asthma preventers at discharge, 269 (47.5%) had one or more prescriptions dispensed in the community within 12 months. Participants who were in the protected period (asthma preventer dispensed) had reduced risk of an asthma hospital readmission (HR 0.61, 95% CI 0.36 to 1.02, p=0.06), including preschool children (HR 0.48, 95% CI 0.25, 0.93, p=0.03) on subgroup analysis. CONCLUSIONS: There was a low rate for prescribing and dispensing of hospital discharge asthma preventers and no protective effect was found for its impact on readmissions. A protective effect on readmissions was found for community asthma preventer dispensing.
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Asma , Readmissão do Paciente , Adulto , Pré-Escolar , Criança , Humanos , Estudos de Coortes , Asma/tratamento farmacológico , Asma/epidemiologia , Asma/prevenção & controle , Hospitalização , Alta do PacienteRESUMO
BACKGROUND: US housing policy places a high priority on homeownership, providing large homeowner subsidies that are justified in part by homeownership's purported health benefits. However, studies conducted before, during, and immediately after the 2007-2010 foreclosure crisis found that while homeownership is associated with better health-related outcomes for White households, that association is weaker or non-existent for African-American and Latinx households. It is not known whether those associations persist in the period since the foreclosure crisis changed the US homeownership landscape. OBJECTIVE: To examine the relationship between homeownership and health and whether that relationship differs by race/ethnicity in the period since the foreclosure crisis. DESIGN: We conducted a cross-sectional analysis of 8 waves (2011-2018) of the California Health Interview Survey (n = 143,854, response rate 42.3 to 47.5%). PARTICIPANTS: We included all US citizen respondents ages 18 and older. MAIN MEASURES: The primary predictor variable was housing tenure (homeownership or renting). The primary outcomes were self-rated health, psychological distress, number of health conditions, and delays in receiving necessary medical care and/or medications. KEY RESULTS: Compared to renting, homeownership is associated with lower rates of reporting fair or poor health (OR = 0.86, P < 0.001), fewer health conditions (incidence rate ratio = 0.95, P = 0.03), and fewer delays in receiving medical care (OR = 0.81, P < 0.001) and medication (OR = 0.78, P < 0.001) for the overall study population. Overall, race/ethnicity was not a significant moderator of these associations in the post-crisis period. CONCLUSIONS: Homeownership has the potential to provide significant health-related benefits to minoritized communities, but this potential may be threatened by practices of racial exclusion and predatory inclusion. Further study is needed to elucidate health-promoting mechanisms within homeownership as well as potential harms of specific homeownership-promoting policies to develop healthier, more equitable housing policy.