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INTRODUCTION: Right ventricular dysfunction is associated with mortality in patients with acute respiratory distress syndrome (ARDS) but information in veno-venous extracorporeal membrane oxygenation (ECMO) settings is limited. Study objectives were to examine factors associated with right ventricular (RV) systolic dysfunction (RVSD) and RV dilation in ECMO patients with ARDS, to compare outcomes in those with and without RVSD and RV dilation defined by qualitative and quantitative parameters, and to describe RVSD evolution during ECMO. METHODS: Retrospective observational study of adult ARDS patients supported with ECMO at a tertiary care hospital. RESULTS: Of a total of 62 patients, 56% had RVSD and 61% had RV dilation by qualitative assessment. Male gender, COVID-19, hypercarbia, and pneumothorax were associated with RVSD and RV dilation. In-hospital mortality was significantly higher in patients with RV dilation vs. no dilation (42% vs. 17%, p = .05) but comparisons for patients with and without RVSD (37% vs. 26%, respectively) did not reach statistical significance. Findings were similar when RV size and function were quantified by right to left ventricle end-diastolic area ratio and fractional area change (39% vs. 21% and 36% vs. 20% respectively; p = NS). Of 39 patients with multiple echocardiograms, 9 of 18 with initially normal RV function developed RVSD while RV function normalized in 10 of 21 patients who began ECMO with RVSD. CONCLUSIONS: Study results suggest an association of RV dilation and RVSD with worse outcomes and a dynamic nature of RV function necessitating close monitoring during the ECMO course.
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In a recent preprint, Park, Metzger, and Thornton reanalyze 20 empirical protein sequence-function landscapes using a "reference-free analysis" (RFA) method they recently developed. They argue that these empirical landscapes are simpler and less epistatic than earlier work suggested, and attribute the difference to limitations of the methods used in the original analyses of these landscapes, which they claim are more sensitive to measurement noise, missing data, and other artifacts. Here, we show that these claims are incorrect. Instead, we find that the RFA method introduced by Park et al. is exactly equivalent to the reference-based least-squares methods used in the original analysis of many of these empirical landscapes (and also equivalent to a Hadamard-based approach they implement). Because the reanalyzed and original landscapes are in fact identical, the different conclusions drawn by Park et al. instead reflect different interpretations of the parameters describing the inferred landscapes; we argue that these do not support the conclusion that epistasis plays only a small role in protein sequence-function landscapes.
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Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium-Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1 month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery-Åsberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected < 0.001, Cohen's d = 0.74) and 1 month (Pcorrected < 0.001, d = 2.20) after treatment and in PTSD (Pcorrected < 0.001, d = 2.54), depression (Pcorrected < 0.001, d = 2.80) and anxiety (Pcorrected < 0.001, d = 2.13) at 1 month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. ClinicalTrials.gov registration: NCT04313712 .
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Lesões Encefálicas Traumáticas , Ibogaína , Veteranos , Humanos , Veteranos/psicologia , Magnésio/uso terapêutico , Resultado do Tratamento , Lesões Encefálicas Traumáticas/tratamento farmacológicoRESUMO
INTRODUCTION: Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrinopathy in women, ranging from 5% to 26% depending on diagnostic criteria applied. Common manifestations of PCOS include overweight and obesity, abnormal menstrual cycles, pelvic pain, increased facial and body hair, acne, and infertility. These abnormalities and associated complications have significant military operational and readiness implications. There is a large gap in research regarding active duty servicewomen (ADW) with PCOS. Therefore, the purpose of this study is to describe ADW's experience of living with PCOS and to describe the service-branch-specific differences among these women. MATERIALS AND METHODS: Moderator's guide, audiotapes, transcripts, and field notes. This was a qualitative descriptive study using focus groups and individual interviews. The David Grant Medical Center Institutional Review Board at Travis AFB, CA, USA, approved the study protocol. Women with PCOS were recruited from U.S. Air Force, Army, and Navy locations. Data were analyzed using constant comparative content analysis. RESULTS: Twenty-three servicewomen from 19 occupations across the Army, Navy, Air Force, and Marine Corps participated. Three overarching categories emerged: (1) challenges managing PCOS symptoms, (2) navigating the military health care system, and (3) navigating PCOS as a service member. CONCLUSIONS: Servicewomen may have significant career consequences related to PCOS sequelae, such as overweight, obesity, uncontrolled menstrual cycle, and pain. Managing the myriad of symptoms can distract women while deployed, in austere conditions, or at their home stations. As one of the most common cardiometabolic, reproductive endocrinologic conditions in women, PCOS has not received the attention, awareness, education, or research necessary to sufficiently support ADW with this condition. It is imperative that evidence-based strategies are developed to inform relevant and high-quality care for these warfighters. Future qualitative studies are needed to further describe specific stressors and needs of ADW with PCOS. Future intervention studies are also needed to evaluate effective management options for ADW with PCOS.
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Infertilidade , Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Sobrepeso/complicações , Infertilidade/complicações , Reprodução , Obesidade/complicações , Obesidade/epidemiologiaRESUMO
INTRODUCTION: The Women in Combat Summit 2021 "Forging the Future: How Women Enhance the Fighting Force" took place during February 9-11, 2021, via a virtual conference platform. The third and final day of the Summit regarded the physical health and well-being of military women and included the topics of urogenital health, nutrition and iron-deficiency anemia, unintended pregnancy and contraception, and traumatic brain injury. MATERIALS AND METHODS: After presentations on the topics earlier, interested conference attendees were invited to participate in focus groups to discuss and review policy recommendations for physical health and well-being in military women. Discussions centered around the topics discussed during the presentations, and suggestions for future Women in Combat Summits were noted. Specifics of the methods of the Summit are presented elsewhere in this supplement. RESULTS: We formulated research and policy recommendations for urogenital health, nutrition and iron-deficiency anemia, contraception and unintended pregnancy, and traumatic brain injury. CONCLUSIONS: In order to continue to develop the future health of military women, health care providers, researchers, and policymakers should consider the recommendations made in this supplement as they continue to build on the state of the science and forge the future.
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Anemia Ferropriva , Lesões Encefálicas Traumáticas , Militares , Gravidez , Humanos , Feminino , Anticoncepção , Gravidez não PlanejadaRESUMO
Racial and ethnic minorities experience high rates of disease morbidity and mortality. Filipinos in Hawai'i have the second-highest coronavirus disease 2019 (COVID-19) cases and deaths. This exploratory study examined barriers to compliance with COVID-19 prevention practices for Filipino immigrants residing in O'ahu and Maui. Cross-sectional data were collected using mixed methods involving surveys and key informant interviews with Filipino community members. Survey responses (n=50) were collected identifying crucial factors to be addressed and preferences for receiving information related to COVID-19. Some Filipino customs and practices were a barrier to complying with COVID-19 prevention practices; nevertheless, cultural sensitivity was stressed for education messaging. In addition, family and community navigators should be equipped with the training and resources to disseminate COVID-19 information within their communities. Attitudinal, cultural, and linguistic barriers to promote health persist for Filipinos in Hawai'i. The COVID-19 pandemic has exacerbated these barriers due to the circulation of misinformation and lack of information among the Filipino communities of O'ahu and Maui regarding COVID-19 and local policies. Culturally appropriate support including providing tailored and linguistically appropriate COVID-19 information is recommended. Equipping or training a household member to help navigate COVID-19 policies as they change aligns with this community's emphasis on familial and social relationships.
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COVID-19 , Promoção da Saúde , Humanos , Havaí/epidemiologia , Estudos Transversais , Pandemias , Dados PreliminaresRESUMO
Our immune systems constantly coevolve with the pathogens that challenge them, as pathogens adapt to evade our defense responses, with our immune repertoires shifting in turn. These coevolutionary dynamics take place across a vast and high-dimensional landscape of potential pathogen and immune receptor sequence variants. Mapping the relationship between these genotypes and the phenotypes that determine immune-pathogen interactions is crucial for understanding, predicting, and controlling disease. Here, we review recent developments applying high-throughput methods to create large libraries of immune receptor and pathogen protein sequence variants and measure relevant phenotypes. We describe several approaches that probe different regions of the high-dimensional sequence space and comment on how combinations of these methods may offer novel insight into immune-pathogen coevolution.
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Adaptação Fisiológica , Fenótipo , GenótipoRESUMO
Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n = 53) had shorter hospital LOS compared to those in warfarin (n = 39) and enoxaparin (n = 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively; P < .0001). This single institution retrospective study suggests DOAC initiation <48 h from thrombolysis may result in shorter hospital LOS compared to DOAC initiation ≥48 h (P < .0001). Further larger studies with more robust research methodology are needed to address this important clinical question.
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Inibidores do Fator Xa , Embolia Pulmonar , Humanos , Estudos Retrospectivos , Inibidores do Fator Xa/uso terapêutico , Rivaroxabana/uso terapêutico , Embolia Pulmonar/tratamento farmacológico , Embolia Pulmonar/induzido quimicamente , Anticoagulantes , Administração Oral , Terapia TrombolíticaRESUMO
The Omicron BA.1 variant of SARS-CoV-2 escapes convalescent sera and monoclonal antibodies that are effective against earlier strains of the virus. This immune evasion is largely a consequence of mutations in the BA.1 receptor binding domain (RBD), the major antigenic target of SARS-CoV-2. Previous studies have identified several key RBD mutations leading to escape from most antibodies. However, little is known about how these escape mutations interact with each other and with other mutations in the RBD. Here, we systematically map these interactions by measuring the binding affinity of all possible combinations of these 15 RBD mutations (215=32,768 genotypes) to 4 monoclonal antibodies (LY-CoV016, LY-CoV555, REGN10987, and S309) with distinct epitopes. We find that BA.1 can lose affinity to diverse antibodies by acquiring a few large-effect mutations and can reduce affinity to others through several small-effect mutations. However, our results also reveal alternative pathways to antibody escape that does not include every large-effect mutation. Moreover, epistatic interactions are shown to constrain affinity decline in S309 but only modestly shape the affinity landscapes of other antibodies. Together with previous work on the ACE2 affinity landscape, our results suggest that the escape of each antibody is mediated by distinct groups of mutations, whose deleterious effects on ACE2 affinity are compensated by another distinct group of mutations (most notably Q498R and N501Y).
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COVID-19 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2/genética , Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Soroterapia para COVID-19 , Mutação , SARS-CoV-2/genética , Evolução MolecularRESUMO
Broadly neutralizing antibodies (bnAbs) that neutralize diverse variants of a particular virus are of considerable therapeutic interest. Recent advances have enabled us to isolate and engineer these antibodies as therapeutics, but eliciting them through vaccination remains challenging, in part due to our limited understanding of how antibodies evolve breadth. Here, we analyze the landscape by which an anti-influenza receptor binding site (RBS) bnAb, CH65, evolved broad affinity to diverse H1 influenza strains. We do this by generating an antibody library of all possible evolutionary intermediates between the unmutated common ancestor (UCA) and the affinity-matured CH65 antibody and measure the affinity of each intermediate to three distinct H1 antigens. We find that affinity to each antigen requires a specific set of mutations - distributed across the variable light and heavy chains - that interact non-additively (i.e., epistatically). These sets of mutations form a hierarchical pattern across the antigens, with increasingly divergent antigens requiring additional epistatic mutations beyond those required to bind less divergent antigens. We investigate the underlying biochemical and structural basis for these hierarchical sets of epistatic mutations and find that epistasis between heavy chain mutations and a mutation in the light chain at the VH-VL interface is essential for binding a divergent H1. Collectively, this is the first work to comprehensively characterize epistasis between heavy and light chain mutations and shows that such interactions are both strong and widespread. Together with our previous study analyzing a different class of anti-influenza antibodies, our results implicate epistasis as a general feature of antibody sequence-affinity landscapes that can potentiate and constrain the evolution of breadth.
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Anticorpos Neutralizantes , Influenza Humana , Humanos , Sítios de Ligação , Ligação Proteica , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da InfluenzaRESUMO
Objective: Assess discrepancy between estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk and observed 10-year event rates in a rural population participating in cardiovascular health initiative. Methods: The study included a rural sample of individuals participating in the Heart of New Ulm (HONU), a population-based health initiative aimed at reducing ASCVD risk in a rural community. HONU conducted over 100 baseline screening events with 5221 individuals participating in 2009. For this analysis, we included participants who were aged 40-79 years, free of ASCVD at baseline, and had adequate data to calculate 10-year ASCVD risk. Electronic health record data and state death records were used to determine rates of non-fatal myocardial infarction and stroke, and ASCVD death from 2010-2019. ASCVD event rates were compared to estimated 10-year risks calculated using the Pooled Cohort Equations, stratified by sex and clinically relevant risk categories. Results: The sample (n = 2819, mean ± SD age 56.1 ± 9.9 years, 59.6% female) had a low prevalence of tobacco use (8.1% current smokers) and diabetes (6.5%) and a high prevalence of hypertension (44.4%) and hyperlipidemia (56.6%). The median estimated 10-year ASCVD risk for the entire sample was 5.7% (IQR 2.3-13.5%) with an observed 10-year ASCVD event rate of 3.4%. The largest gap between observed and estimated risk was in those at intermediate/high (≥7.5%) ASCVD risk (median 10-year risk 15.8% [IQR 10.4-29.0], observed ASCVD event rate 6.4%). Conclusio: In a sample of rural participants exposed to a multifaceted ASCVD prevention initiative, observed rates of ASCVD were substantially lower compared to estimated ASCVD risk. The potential for significantly lower than predicted ASCVD event rates in certain populations should be included in the clinician-patient risk discussion.
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The Military Women's Health Research Interest Group (MWHRIG) was established in 2010. The purpose of the MWHRIG is to support military clinicians and leaders in determining research priorities, and making evidence-based practice and policy decisions relevant to sex- and gender-appropriate healthcare. This article highlights the history of the MWHRIG, and current activities inclusive of research, mentorship, and collaboration. Future activities for the MWHRIG will focus on continued use of a theoretical framework for military women's health research, inclusivity of gender sexual diversity (GSD), and metrics for future success.
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Militares , Feminino , Humanos , Opinião Pública , Saúde da Mulher , Prática Clínica Baseada em Evidências , Identidade de GêneroRESUMO
Neuropathy is a painful and potentially devastating complication of diabetes mellitus affecting many patients. Neuropathy can lead to foot ulcers, infections, and subsequent amputations. Nerve damage from peripheral neuropathy may lead to Charcot neuropathic osteoarthropathy, commonly known as Charcot foot. Flesh wounds and weakened bones causing microfractures of the foot and ankle may lead to foot malformations. Early recognition and care are essential for the treatment of Charcot foot and prevention of further injury. This article discusses the use of monofilament testing for diabetic neuropathy, increasing awareness of Charcot foot, and introducing a screening algorithm for Charcot foot.
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Artropatia Neurogênica , Pé Diabético , Neuropatias Diabéticas , Humanos , Artropatia Neurogênica/diagnóstico , Artropatia Neurogênica/terapia , Artropatia Neurogênica/etiologia , Pé Diabético/diagnóstico , Pé Diabético/complicações , Neuropatias Diabéticas/complicações , DorRESUMO
The Omicron BA.1 variant emerged in late 2021 and quickly spread across the world. Compared to the earlier SARS-CoV-2 variants, BA.1 has many mutations, some of which are known to enable antibody escape. Many of these antibody-escape mutations individually decrease the spike receptor-binding domain (RBD) affinity for ACE2, but BA.1 still binds ACE2 with high affinity. The fitness and evolution of the BA.1 lineage is therefore driven by the combined effects of numerous mutations. Here, we systematically map the epistatic interactions between the 15 mutations in the RBD of BA.1 relative to the Wuhan Hu-1 strain. Specifically, we measure the ACE2 affinity of all possible combinations of these 15 mutations (215 = 32,768 genotypes), spanning all possible evolutionary intermediates from the ancestral Wuhan Hu-1 strain to BA.1. We find that immune escape mutations in BA.1 individually reduce ACE2 affinity but are compensated by epistatic interactions with other affinity-enhancing mutations, including Q498R and N501Y. Thus, the ability of BA.1 to evade immunity while maintaining ACE2 affinity is contingent on acquiring multiple interacting mutations. Our results implicate compensatory epistasis as a key factor driving substantial evolutionary change for SARS-CoV-2 and are consistent with Omicron BA.1 arising from a chronic infection.
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Enzima de Conversão de Angiotensina 2 , COVID-19 , Humanos , Enzima de Conversão de Angiotensina 2/genética , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/metabolismo , Peptidil Dipeptidase A/metabolismo , Epistasia Genética , COVID-19/genéticaRESUMO
Mental health disorders and substance use disorders are a leading cause of morbidity and mortality worldwide, and one of the most important challenges for public health systems. While evidence-based psychotherapy is generally pursued to address mental health challenges, psychological change is often hampered by non-adherence to treatments, relapses, and practical barriers (e.g., time, cost). In recent decades, Non-invasive brain stimulation (NIBS) techniques have emerged as promising tools to directly target dysfunctional neural circuitry and promote long-lasting plastic changes. While the therapeutic efficacy of NIBS protocols for mental illnesses has been established, neuromodulatory interventions might also be employed to support the processes activated by psychotherapy. Indeed, combining psychotherapy with NIBS might help tailor the treatment to the patient's unique characteristics and therapeutic goal, and would allow more direct control of the neuronal changes induced by therapy. Herein, we overview emerging evidence on the use of NIBS to enhance the psychotherapeutic effect, while highlighting the next steps in advancing clinical and research methods toward personalized intervention approaches.
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Transtornos Relacionados ao Uso de Substâncias , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Magnética Transcraniana/métodos , Estimulação Transcraniana por Corrente Contínua/métodos , Psicoterapia/métodos , Transtornos Relacionados ao Uso de Substâncias/terapia , Encéfalo/fisiologiaRESUMO
OBJECTIVE: This article offers a recommendation on how the Pediatric Assessment Emergence Delirium Scale (PAEDS) could be implemented in the post anesthesia care unit (PACU) to improve the assessment and treatment of pediatric emergence delirium (PED). BACKGROUND: PED is an anticipated complication in the PACU characterized by mental confusion, irritability, disorientation, inconsolable crying, and prolonged postanesthetic recovery time. Although it is a short-lived phenomenon, it increases the risk for traumatic injuries and may lead to a decrease in overall parent satisfaction with their child's surgical experience. METHOD: Implementation of the PAEDS in the PACU has the potential to improve the care and safety of the surgical pediatric patient population and could be a catalyst for PED process improvements. This tool has been used in various studies and has demonstrated the validity and reliability in the assessment of emergence delirium. CONCLUSIONS: Clinical use of the PAEDS is not standard of practice, but considering the adverse effects of PED on patients, parents, and medical staff, a PAEDS protocol could be beneficial to the PACU.
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Delírio do Despertar , Humanos , Criança , Delírio do Despertar/epidemiologia , Período de Recuperação da Anestesia , Melhoria de Qualidade , Reprodutibilidade dos Testes , Anestesia Geral/métodos , Estudos ProspectivosRESUMO
Neuropsychiatric disorders including generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ) have been considered distinct categories of diseases despite their overlapping characteristics and symptomatology. We aimed to provide an in-depth review elucidating the role of glutamate/Glx and white matter (WM) abnormalities in these disorders from a transdiagnostic perspective. The PubMed online database was searched for studies published between 2010 and 2021. After careful screening, 401 studies were included. The findings point to decreased levels of glutamate in the Anterior Cingulate Cortex in both SZ and BD, whereas Glx is elevated in the Hippocampus in SZ and MDD. With regard to WM abnormalities, the Corpus Callosum and superior Longitudinal Fascicle were the most consistently identified brain regions showing decreased fractional anisotropy (FA) across all the reviewed disorders, except GAD. Additionally, the Uncinate Fasciculus displayed decreased FA in all disorders, except OCD. Decreased FA was also found in the inferior Longitudinal Fasciculus, inferior Fronto-Occipital Fasciculus, Thalamic Radiation, and Corona Radiata in SZ, BD, and MDD. Decreased FA in the Fornix and Corticospinal Tract were found in BD and SZ patients. The Cingulum and Anterior Limb of Internal Capsule exhibited decreased FA in MDD and SZ patients. The results suggest a gradual increase in severity from GAD to SZ defined by the number of brain regions with WM abnormality which may be partially caused by abnormal glutamate levels. WM damage could thus be considered a potential marker of some of the main neuropsychiatric disorders.
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Transtorno Bipolar , Transtorno Depressivo Maior , Substância Branca , Anisotropia , Transtorno Bipolar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Transtorno Depressivo Maior/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Ácido Glutâmico , Humanos , Substância Branca/diagnóstico por imagemRESUMO
The sequence space accessible to evolving proteins can be enhanced by cellular chaperones that assist biophysically defective clients in navigating complex folding landscapes. It is also possible, at least in theory, for proteostasis mechanisms that promote strict quality control to greatly constrain accessible protein sequence space. Unfortunately, most efforts to understand how proteostasis mechanisms influence evolution rely on artificial inhibition or genetic knockdown of specific chaperones. The few experiments that perturb quality control pathways also generally modulate the levels of only individual quality control factors. Here, we use chemical genetic strategies to tune proteostasis networks via natural stress response pathways that regulate the levels of entire suites of chaperones and quality control mechanisms. Specifically, we upregulate the unfolded protein response (UPR) to test the hypothesis that the host endoplasmic reticulum (ER) proteostasis network shapes the sequence space accessible to human immunodeficiency virus-1 (HIV-1) envelope (Env) protein. Elucidating factors that enhance or constrain Env sequence space is critical because Env evolves extremely rapidly, yielding HIV strains with antibody- and drug-escape mutations. We find that UPR-mediated upregulation of ER proteostasis factors, particularly those controlled by the IRE1-XBP1s UPR arm, globally reduces Env mutational tolerance. Conserved, functionally important Env regions exhibit the largest decreases in mutational tolerance upon XBP1s induction. Our data indicate that this phenomenon likely reflects strict quality control endowed by XBP1s-mediated remodeling of the ER proteostasis environment. Intriguingly, and in contrast, specific regions of Env, including regions targeted by broadly neutralizing antibodies, display enhanced mutational tolerance when XBP1s is induced, hinting at a role for host proteostasis network hijacking in potentiating antibody escape. These observations reveal a key function for proteostasis networks in decreasing instead of expanding the sequence space accessible to client proteins, while also demonstrating that the host ER proteostasis network profoundly shapes the mutational tolerance of Env in ways that could have important consequences for HIV adaptation.
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Infecções por HIV , Proteostase , Retículo Endoplasmático/metabolismo , Estresse do Retículo Endoplasmático/genética , Infecções por HIV/metabolismo , Humanos , Chaperonas Moleculares/metabolismo , Resposta a Proteínas não DobradasRESUMO
INTRODUCTION: The cesarean birth rate of 24.7% in the Military Health System (MHS) is lower than the national rate of 31.7%. However, the MHS rate remains higher than the 15-19% threshold associated with optimal maternal and neonatal outcomes. For active duty servicewomen, increased morbidity associated with cesarean birth is likely to affect the ability to meet the demands of assigned missions. Several decision-points occur during pregnancy and after the onset of labor that can affect the likelihood of cesarean birth including choice of provider, choice of hospital, timing of admission, and type of fetal monitoring. Evidence suggests the overuse of labor interventions may be associated with cesarean birth. Shared decision-making (SDM) is a strategy that can be used to carefully consider the risks, benefits, and alternatives of each labor intervention and is shown to be associated with positive patient outcomes. Most existing evidence explores SDM as an interaction that occurs between women and their providers. Few studies have explored the role of stakeholders such as spouses, family members, friends, labor and delivery nurses, and doulas. Furthermore, little is known about the process of SDM during labor and childbirth in the hospital setting, particularly for active duty women in the U.S. military. The purpose of this study was to propose a framework that explains the process of SDM during labor and childbirth in the hospital setting for active duty women in the U.S. military. MATERIALS AND METHODS: A qualitatively driven mixed-methods approach was conducted to propose a framework that explains the process of SDM during labor and childbirth in the hospital setting for active duty women in the U.S. military. Servicewomen were recruited from September 2019 to April 2020. Semi-structured interviews were analyzed using a constructivist grounded theory approach. Participants also completed the SDM Questionnaire (SDM-Q-9). RESULTS: Interviews were conducted with 14 participants. The sample included servicewomen from the Air Force (n = 7), Army (n = 4), and Navy (n = 3). Two participants were enlisted and the remainder were officers. Ten births occurred at military treatment facilities (MTFs) and four births took place at civilian facilities. The mean score on the SDM Questionnaire was 86.7 (±11.6), indicating a high level of SDM. Various stakeholders (e.g., providers, labor and delivery nurses, doulas, spouses, family members, and friends) were involved in SDM at different points during labor and birth. The four stages of SDM included gathering information, identifying preferences, discussing options, and making decisions. Events that most often involved SDM were deciding when to travel to the hospital, deciding when to be admitted, and selecting a strategy for pain management. Military factors involved in SDM included sources of information, selecting and working with civilian providers, and delaying labor interventions to allow time for an active duty spouse to travel to the hospital. CONCLUSIONS: SDM during labor and birth in the hospital setting is a multi-stage process that involves a variety of stakeholders, including the woman, members of her social and support network, and healthcare professionals. Future research is needed to explore perspectives of other stakeholders involved in SDM.
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Cesárea , Parto , Tomada de Decisões , Família , Feminino , Humanos , Recém-Nascido , Gravidez , RiscoRESUMO
OBJECTIVE: To examine the extent to which racial disparities exist in the perinatal outcomes of beneficiaries of the Military Health System (MHS). DATA SOURCES: We searched the PubMed, CINAHL, and Embase databases. STUDY SELECTION: We selected articles published in English in peer-reviewed journals in which the authors examined race in relation to perinatal outcomes among beneficiaries of the MHS. Date of publication was unrestricted through March 2021. DATA EXTRACTION: Twenty-six articles met the inclusion criteria. We extracted data about study design, purpose, sample, setting, and results. We also assigned quality appraisal ratings to each article. DATA SYNTHESIS: In most of the included articles, researchers observed differences in perinatal outcomes between Black and White women. Compared to White women, Black women had greater rates of cesarean birth, preterm birth, low birth weight, and small for gestational age neonates. White women had greater rates of postpartum depression than Black women. CONCLUSION: Racial disparities in very low birth weight newborns and preterm birth may be smaller in the MHS than in the general population of the United States. The overall rates of preterm birth, cesarean birth, and neonatal mortality were lower for beneficiaries of the MHS than in the general population of the United States.