RESUMO
The VPS13 protein family constitutes a novel class of bridge-like lipid transferases. Autosomal recessive inheritance of mutations in VPS13 genes is associated with the development of neurodegenerative diseases in humans. Bioinformatic approaches previously recognized the domain architecture of these proteins. In this study, we model the first ever full-length structures of the four human homologs VPS13A, VPS13B, VPS13C, and VPS13D in association with model membranes, to investigate their lipid transfer ability and potential structural association with membrane leaflets. We analyze the evolutionary conservation and physicochemical properties of these proteins, focusing on conserved C-terminal amphipathic helices that disturb organelle surfaces and that, adjoined, resemble a traditional Venetian gondola. The gondola domains share significant structural homology with lipid droplet surface-binding proteins. We introduce in silico protein-membrane models displaying the mode of association of VPS13A, VPS13B, VPS13C, and VPS13D to donor and target membranes, and present potential models of action for protein-mediated lipid transfer.
Assuntos
Lipídeos , Proteínas de Transporte Vesicular , Humanos , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Membranas/metabolismo , Mutação , Estrutura Secundária de Proteína , Proteínas/genéticaRESUMO
One hurdle in the development of zebrafish models of human disease is the presence of multiple zebrafish orthologs resulting from whole genome duplication in teleosts. Mutations in inositol polyphosphate 5-phosphatase K (INPP5K) lead to a syndrome characterized by variable presentation of intellectual disability, brain abnormalities, cataracts, muscle disease, and short stature. INPP5K is a phosphatase acting at position 5 of phosphoinositides to control their homeostasis and is involved in insulin signaling, cytoskeletal regulation, and protein trafficking. Previously, our group and others have replicated the human phenotypes in zebrafish knockdown models by targeting both INPP5K orthologs inpp5ka and inpp5kb. Here, we show that inpp5ka is the more closely related orthologue to human INPP5K. While both inpp5ka and inpp5kb mRNA expression levels follow a similar trend in the developing head, eyes, and tail, inpp5ka is much more abundantly expressed in these tissues than inpp5kb. In situ hybridization revealed a similar trend, also showing unique localization of inpp5kb in the pineal gland and retina indicating different transcriptional regulation. We also found that inpp5kb has lost its catalytic activity against its preferred substrate, PtdIns(4,5)P2. Since most human mutations are missense changes disrupting phosphatase activity, we propose that loss of inpp5ka alone can be targeted to recapitulate the human presentation. In addition, we show that the function of inpp5kb has diverged from inpp5ka and may play a novel role in the zebrafish.
Assuntos
Regulação da Expressão Gênica , Peixe-Zebra , Animais , Humanos , Inositol , Mutação , Monoéster Fosfórico Hidrolases/genética , Monoéster Fosfórico Hidrolases/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/metabolismoRESUMO
Good quality patient care requires health care providers to respect the humanity and autonomy of their patients. However, this is not achieved in all settings. This study used cross-sectional survey data including open-ended text responses to explore negative experiences with health care providers among women in Appalachia. We used the Heath Stigma & Discrimination Framework (HSDF) to identify how stigma is created and perpetuated through interactions with health care providers. Survey data from 628 women collected through purposive sampling identified that two out of three participants had had a bad encounter with a provider that made them not want to return for care. One in six participants had a negative experience specifically while seeking contraception. Using the domains of the HSDF framework, qualitative answers to open-ended questions illuminated how health care providers, influenced by social and cultural norms related to religiosity, patriarchal views, poverty, poor health infrastructure, and the opioid crisis, created and perpetuated stigma through dehumanising treatment, low-quality care, and health care misogyny. Because stigma is a driver of health inequity, these findings highlight the important and sometimes problematic role that health care providers can play when they create a barrier to future care through poor treatment of patients.
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Instalações de Saúde , Estigma Social , Humanos , Feminino , Estudos Transversais , Região dos Apalaches , Acessibilidade aos Serviços de SaúdeRESUMO
Somali refugee youth present with a heightened risk for common mental disorders (CMDs), and yet few studies have discussed factors influencing mental health outcomes after psychosocial interventions. This study aimed to identify key factors that contribute to the improvement of CMD symptoms among Somali youth displaced in urban Kenya. Logistic regression analyses revealed that trauma exposure and emotional coping predict overall symptom improvement, pointing to a differential intervention effect on those with differing levels of religious belief and attitudes toward violence. This study provides insights into how psychosocial factors likely contribute to positive intervention outcomes in Somali refugee youth.
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Transtornos Mentais , Refugiados , Adaptação Psicológica , Adolescente , Humanos , Quênia , Refugiados/psicologia , SomáliaRESUMO
This paper introduces culturally responsive and trauma-informed mental health training modules to build and enhance competences and partnerships among mental health professionals and refugee community leaders, while facilitating intercultural, mutual learning between participants from various cultural and professional backgrounds. Focus group interviews and participant self-reflections with the training participants (N = 54) were analyzed using thematic analysis. Findings revealed an enhanced understanding of culturally unique as well as universal trauma responses and coping in the refugee community, which led to the building and strengthening of a sense of community and an expansion of social networks and support systems. This study highlights the effectiveness of interactive learning and knowledge transference among participants with various cultural and professional backgrounds, showing that face-to-face interactions and mutual learning reportedly facilitated building relationships and trust among participants and especially those between refugee/immigrant community leaders and service providers.
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Emigrantes e Imigrantes , Refugiados , Comparação Transcultural , Grupos Focais , Humanos , Aprendizagem , Refugiados/psicologiaRESUMO
BACKGROUND: Contraceptive access is influenced by policy decisions, which can expand and constrict the contraceptive options available. This study explored the impact of recent US federal policy on contraceptive access. METHODS: Federal policy changes impacting contraceptive access over the past decade were identified in grey literature. These policy changes were organized into a timeline and analyzed according to Levesque et al.'s (2013) five dimensions of healthcare access (approachability, acceptability, availability/accommodation, affordability, and appropriateness), noting the most salient healthcare dimension impacted by the policy change and analyzing whether, according to this framework, the policy created a theoretical increase or decrease in contraceptive access. RESULTS: Of those policy changes coded as increasing (n = 42) and decreasing (n = 28) contraceptive access, most were related to the affordability (increasing n = 13; decreasing n = 12), physical availability (increasing n = 10; decreasing n = 7), and appropriateness (increasing n = 12; decreasing n = 4) of contraceptive care. Policy changes largely followed partisan divides, with contraceptive access increasing in years with a Democratic president and decreasing when a Republican president was in office. Many policy changes were related to the Affordable Care Act (ACA) and Title X of the Public Health Services Act. The implementation of the ACA and subsequent updates to it have increased the affordability of contraception, whereas changes to Title X have decreased the availability and appropriateness of contraceptive care. CONCLUSIONS: This study highlights recent policy changes impacting contraceptive access, organizing them according to the five dimensions of healthcare access. It outlines specific policy barriers to contraceptive access and provides suggestions for policy and practice action that will improve contraceptive access and reproductive autonomy. Opportunities to ensure contraceptive access for all Americans include promoting comprehensive sex education, extending the Community Health Center Fund, increasing contraceptive care options for people with employers who are exempted from the ACA contraceptive mandate, addressing discrimination and building trust in contraceptive care, and amplifying outreach efforts to combat misinformation and confusion created by continuous changes to key family planning policies. Continued research on the role of policy in determining reproductive autonomy is warranted, and practice and policy action is needed to improve contraceptive access.
Legislation influences if, when, and how people access contraception. Healthcare access can be conceptualized across five dimensions: approachability, acceptability, availability/accommodation, affordability, and appropriateness. Applying this healthcare access framework can help understand barriers to and facilitators of contraceptive access. In this study, I conducted a systematic Google search to identify recent federal policy changes related to contraceptive access. I organized these policy changes into a timeline and analyzed them according to the healthcare access framework mentioned above. Through this analysis, I have highlighted specific policy barriers to contraceptive access and provided suggestions for policy and practice action that can improve contraceptive access and reproductive autonomy.Findings indicated that Levesque et al.'s (2013) dimensions of healthcare access are relevant to contraceptive care. Many recent US policy changes related to contraceptive access are described in this study, and the analysis showed that these policy changes have fluctuated with election cycles and according to partisan divides. Two key US policies related to contraceptive access, the Affordable Care Act and Title X of the Public Health Services Act, have sustained many changes across the past decade. These policies have increased contraceptive access in the United States by dedicating funding to family planning availability and affordability and increasing insurance coverage for contraceptive care. However, recent changes to these policies threaten contraceptive access and reproductive autonomy. There is a need for continued research regarding the ways that policy influences reproductive autonomy and a need for practice and policy action to improve contraceptive access.
Assuntos
Política de Planejamento Familiar , Patient Protection and Affordable Care Act , Anticoncepção , Acessibilidade aos Serviços de Saúde , Humanos , Formulação de Políticas , Estados UnidosRESUMO
Congenital muscular dystrophies display a wide phenotypic and genetic heterogeneity. The combination of clinical, biochemical, and molecular genetic findings must be considered to obtain the precise diagnosis and provide appropriate genetic counselling. Here we report five individuals from four families presenting with variable clinical features including muscular dystrophy with a reduction in dystroglycan glycosylation, short stature, intellectual disability, and cataracts, overlapping both the dystroglycanopathies and Marinesco-Sjögren syndrome. Whole-exome sequencing revealed homozygous missense and compound heterozygous mutations in INPP5K in the affected members of each family. INPP5K encodes the inositol polyphosphate-5-phosphatase K, also known as SKIP (skeletal muscle and kidney enriched inositol phosphatase), which is highly expressed in the brain and muscle. INPP5K localizes to both the endoplasmic reticulum and to actin ruffles in the cytoplasm. It has been shown to regulate myoblast differentiation and has also been implicated in protein processing through its interaction with the ER chaperone HSPA5/BiP. We show that morpholino-mediated inpp5k loss of function in the zebrafish results in shortened body axis, microphthalmia with disorganized lens, microcephaly, reduced touch-evoked motility, and highly disorganized myofibers. Altogether these data demonstrate that mutations in INPP5K cause a congenital muscular dystrophy syndrome with short stature, cataracts, and intellectual disability.
Assuntos
Distrofia Muscular do Cíngulo dos Membros/genética , Monoéster Fosfórico Hidrolases/genética , Degenerações Espinocerebelares/genética , Adolescente , Adulto , Sequência de Aminoácidos , Animais , Encéfalo/metabolismo , Criança , Modelos Animais de Doenças , Distroglicanas/metabolismo , Retículo Endoplasmático/metabolismo , Chaperona BiP do Retículo Endoplasmático , Feminino , Estudo de Associação Genômica Ampla , Glicosilação , Transtornos do Crescimento/genética , Humanos , Deficiência Intelectual/genética , Masculino , Microcefalia/genética , Músculo Esquelético/metabolismo , Mutação , Linhagem , Adulto Jovem , Peixe-Zebra/genéticaRESUMO
Phosphoinositides are small phospholipids that control diverse cellular downstream signaling events. Their spatial and temporal availability is tightly regulated by a set of specific lipid kinases and phosphatases. Congenital muscular dystrophies are hereditary disorders characterized by hypotonia and weakness from birth with variable eye and central nervous system involvement. In individuals exhibiting congenital muscular dystrophy, early-onset cataracts, and mild intellectual disability but normal cranial magnetic resonance imaging, we identified bi-allelic mutations in INPP5K, encoding inositol polyphosphate-5-phosphatase K. Mutations impaired phosphatase activity toward the phosphoinositide phosphatidylinositol (4,5)-bisphosphate or altered the subcellular localization of INPP5K. Downregulation of INPP5K orthologs in zebrafish embryos disrupted muscle fiber morphology and resulted in abnormal eye development. These data link congenital muscular dystrophies to defective phosphoinositide 5-phosphatase activity that is becoming increasingly recognized for its role in mediating pivotal cellular mechanisms contributing to disease.
Assuntos
Catarata/genética , Disfunção Cognitiva/genética , Distrofia Muscular do Cíngulo dos Membros/genética , Anormalidades Musculoesqueléticas/genética , Monoéster Fosfórico Hidrolases/genética , Adolescente , Adulto , Alelos , Animais , Encéfalo/patologia , Criança , Pré-Escolar , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Estudo de Associação Genômica Ampla , Humanos , Lactente , Deficiência Intelectual/genética , Imageamento por Ressonância Magnética , Masculino , Músculo Esquelético/patologia , Mutação , Linhagem , Adulto Jovem , Peixe-Zebra/embriologia , Peixe-Zebra/genéticaRESUMO
Female genital mutilation or circumcision (FGM/C) is a perilous social and cultural practice that affects the physical, mental, and psychological health of affected women. It is widespread around the world, affecting 200 million women and girls. This study aimed to explore the relation of FGM/C to mental and physical conditions in Somali refugees displaced in a low-resource setting, applying the concept of poly-victimization to reveal multifaceted trauma sequelae. Data for this cross-sectional study with 143 female Somali youth living in Eastleigh, Kenya were collected between April and May in 2013. FGM/C was strongly associated with negative physical and mental health outcomes, including post-traumatic stress disorder and depressive, anxiety, and somatic symptoms. Logistic regression analysis revealed that separation from a parent and poly-victimization experiences were significantly associated with FGM/C experience. The results also showed that FGM/C and other traumas did not occur singly but were indicative of cumulative adversities, especially for women who were socially vulnerable and marginalized. The results of this study highlight the practice of FGM/C in the context of other adverse living conditions of refugees and the importance of attending to other co-occurring risk factors that prevail with FGM/C practice in the ecological system of refugee forced migration.
Assuntos
Circuncisão Feminina/psicologia , Vítimas de Crime/psicologia , Saúde Mental/estatística & dados numéricos , Trauma Psicológico/epidemiologia , Refugiados/psicologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Quênia/epidemiologia , Fatores de Risco , Somália/etnologia , Adulto JovemAssuntos
Abortivos , Aborto Induzido , Médicos , Humanos , Feminino , Gravidez , Anticoncepcionais , AnticoncepçãoAssuntos
Abortivos , Aborto Induzido , Médicos , Humanos , Feminino , Gravidez , Anticoncepção , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
Clathrin-mediated endocytosis is a major route for the retrieval of plasma-membrane cargoes, and defects of this process can cause catastrophic human dysfunctions. However, the processes governing how a clathrin-coated profile (ccp) is initiated are still murky. Despite an ever-growing cast of molecules proposed as triggers of ccp nucleation and increasingly sophisticated bioimaging techniques examining clathrin-mediated endocytosis, it is yet unknown if ccp formation is governed by a universal mechanism. A recent paper by Cocucci et al. has tracked single-molecule events to identify that stable accumulation of ccps requires the near-simultaneous arrival of two AP2 adaptors bridged by one clathrin triskelion. This commentary examines the role of AP2 in cargo-mediated endocytosis in the light of recent advances in biophotonics, chemical inhibitors and genetics, examines the claims of other molecules to be the initiators of ccp formation and proposes future directions in research into this topic. Editor's suggested further reading in BioEssays: The evolution of dynamin to regulate clathrin-mediated endocytosis Abstract Clathrin-mediated endocytosis: What works for small, also works for big Abstract.
Assuntos
Complexo 2 de Proteínas Adaptadoras/metabolismo , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Vesículas Revestidas por Clatrina/metabolismo , Clatrina/metabolismo , Invaginações Revestidas da Membrana Celular/metabolismo , Endocitose , Complexo 2 de Proteínas Adaptadoras/química , Proteínas Adaptadoras de Transporte Vesicular/química , Animais , Clatrina/química , Vesículas Revestidas por Clatrina/química , Invaginações Revestidas da Membrana Celular/química , Proteínas de Ligação a Ácido Graxo , Humanos , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Fosfatidilinositol 4,5-Difosfato/metabolismo , Domínios e Motivos de Interação entre Proteínas , Fatores de Tempo , Peixe-ZebraRESUMO
This study examines the factors influencing physical health status, specifically focusing on the gender differences in risk and promotive factors affecting health outcomes among Somali refugee youth displaced in Nairobi, Kenya (n = 227). A survey was used to assess participants' physical health along with psychosocial factors, somatic symptoms, and demographic characteristics. The study shows that religious belief and somatic symptoms among the total sample were significant predictors in influencing the outcome of physical health. A moderated mediation analysis and logistic regression analyses also revealed gender differences in associated factors as well as health status; female participants reported higher somatic symptoms, associated with a decline in physical health, whereas the protective effect of social support and religious belief promote was found only among male counterparts. Future studies and interventions would be benefited from a gender-specific approach to health promotion and coping mechanisms in this population.
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Sintomas Inexplicáveis , Refugiados , Humanos , Masculino , Feminino , Adolescente , Somália , Quênia , Apoio Social , Religião , Avaliação de Resultados em Cuidados de SaúdeRESUMO
Despite growing concerns over coercion in contraceptive care, few studies have described its frequency and manifestations. Further, there is no established quantitative method of measuring this construct. We begin to fill this gap by detailing nuance in contraceptive coercion experiences and testing a novel measure: the Coercion in Contraceptive Care Checklist. In early 2023, we surveyed reproductive-aged people in the United States who were assigned female at birth about their contraceptive care. We describe the frequency of contraceptive coercion in our sample (N = 1197) and use open-ended descriptions to demonstrate nuances in these experiences. Finally, we debut our checklist and present psychometric testing results. Among people who had ever talked to a healthcare provider about contraception, over one in six participants (18.46%) reported experiencing coercion during their last contraceptive counseling, and over one in three (42.27%) reported it at some point in their lifetime. Being made to use or keep using birth control pills was the most common form of coercion reported by patients (14.62% lifetime frequency). Factor analysis supported the two-factor dimensionality of the Coercion in Contraceptive Care Checklist. Inter-item correlations were statistically significant (p < 0.001), providing evidence of reliability. The checklist was also related to measures of quality in family planning care (downward coercion: t[1194] = 7.54, p < 0.001; upward coercion: t[1194] = 14.76, p < 0.001) and discrimination in healthcare (downward coercion: t[1160] = -14.77, p < 0.001; upward coercion: t[1160] = -18.27, p < 0.001), providing evidence of construct validity. Findings provide critical information about the frequency and manifestations of contraceptive coercion. Psychometric tests reveal evidence of the Coercion in Contraceptive Care Checklist's validity, reliability, and dimensionality while also suggesting avenues for future testing and refinement.
Assuntos
Coerção , Anticoncepção , Humanos , Feminino , Adulto , Estados Unidos , Adulto Jovem , Adolescente , Pessoal de Saúde/psicologia , Psicometria , Inquéritos e Questionários , Pessoa de Meia-Idade , Comportamento Contraceptivo/psicologia , Comportamento Contraceptivo/estatística & dados numéricosRESUMO
Prior research has found that a high level of residential racial segregation, or the degree to which racial/ethnic groups are isolated from one another, is associated with worsened infant health outcomes, particularly among non-Hispanic (NH) Black infant populations. However, because exposure to segregation is non-random, it is unclear whether and to what extent segregation is causally linked to infant health. To overcome this empirical limitation, we leverage exogenous variation in the placement of railroad tracks in the 19th century to predict contemporary segregation, an approach first introduced by Ananat (2011). In alignment with prior literature, we find that residential segregation has statistically significant associations with negative birth outcomes among Black infant populations in the area. Using OLS methods underestimates the negative impacts of segregation on infant health. We fail to detect comparable effects on health outcomes among NH White infant populations. Further, we identify several key mechanisms by which residential segregation could influence health outcomes among Black infant populations, including lower access to prenatal care during the first trimester, higher levels of anti-Black prejudice, greater transportation barriers, and increased food insecurity. Given that poor birth outcomes have adverse effects on adults' health and well-being, the findings suggest that in-utero exposure to residential segregation could have important implications for Black-White inequality over the life course.
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Saúde do Lactente , Segregação Social , Humanos , Feminino , Lactente , Negro ou Afro-Americano/estatística & dados numéricos , Recém-Nascido , Gravidez , Estados Unidos , Masculino , Características de Residência , Adulto , Disparidades nos Níveis de SaúdeRESUMO
Mutations of the inositol 5' phosphatase oculocerebrorenal syndrome of Lowe (OCRL) give rise to the congenital X-linked disorders oculocerebrorenal syndrome of Lowe and Dent disease, two conditions giving rise to abnormal kidney proximal tubule reabsorption, and additional nervous system and ocular defects in the case of Lowe syndrome. Here, we identify two closely related endocytic proteins, Ses1 and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and Rho-GTPase Activating Domain-like) domain of OCRL. The interaction is mediated by a short amino acid motif similar to that used by the rab-5 effector APPL1 (Adaptor Protein containing pleckstrin homology [PH] domain, PTB domain and Leucine zipper motif 1) APPL1 for OCRL binding. Ses binding is mutually exclusive with APPL1 binding, and is disrupted by the same missense mutations in the ASH-RhoGAP-like domain that also disrupt APPL1 binding. Like APPL1, Ses1 and -2 are localized on endosomes but reside on different endosomal subpopulations. These findings define a consensus motif (which we have called a phenylalanine and histidine [F&H] motif) for OCRL binding and are consistent with a scenario in which Lowe syndrome and Dent disease result from perturbations at multiple sites within the endocytic pathway.
Assuntos
Proteínas de Transporte/metabolismo , Endossomos/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Motivos de Aminoácidos , Sequência de Aminoácidos , Sequência Conservada , Endocitose , Humanos , Dados de Sequência Molecular , Mutação de Sentido Incorreto , Síndrome Oculocerebrorrenal/genética , Síndrome Oculocerebrorrenal/metabolismo , Monoéster Fosfórico Hidrolases/genética , Estrutura Terciária de Proteína , Proteínas de Transporte Vesicular/genéticaRESUMO
Reproductive coercion (RC) is a type of intimate partner violence (IPV) characterized by partner interference with contraception or reproductive decision-making. Despite sexual minority people's vulnerability to other forms of IPV, limited research has examined reproductive coercion in this population. Research on behavioral health impacts of reproductive coercion is also lacking, especially for sexual minorities. This study addressed these gaps by examining the occurrence and behavioral health impact of reproductive coercion among emerging adults, including both heterosexual and sexual minority people. In 2020, survey data were collected with emerging adults (aged 18-24 years) at a university in the southeastern United States (N = 387). We conducted bivariate analyses to explore associates of reproductive coercion and logistic regression to identify risk factors. We then conducted linear regression to investigate relationships between reproductive coercion and behavioral health outcomes, in the full sample and in separate models based on sexual attraction. One in 15 sampled students (6.3%) had experienced reproductive coercion. Sexual attraction was a significant risk factor for reproductive coercion, with increased rates among plurisexual (i.e., attracted to people of multiple genders) compared to monosexual students, in both bivariate (χ2(2) = 7.57, p = .023) and regression analyses (B = 1.25, p = .012). Reproductive coercion was associated with worse behavioral health outcomes in bivariate and regression analyses (anxiety: B = 3.77, p = .001; depression: B = 3.26, p = .010; alcohol use: B = 2.32, p < .001). In separate linear regression models based on sexual attraction, RC was significantly associated with behavioral health indicators for participants who were attracted only to men and those attracted to people of multiple genders but not for participants who were attracted only to women. Findings indicated increased RC risk for plurisexual students compared to monosexuals and showed significant associations between RC and behavioral health outcomes, with differential effects based on sexual attraction. These novel findings support the need for continued research on RC, inclusive of nuanced conceptualizations of sexuality.
Assuntos
Violência por Parceiro Íntimo , Minorias Sexuais e de Gênero , Adulto , Humanos , Feminino , Masculino , Heterossexualidade , Parceiros Sexuais , Coerção , Prevalência , Saúde ReprodutivaRESUMO
OBJECTIVE: To investigate the frequency and impact of contraceptive coercion in the Appalachian region of the United States. DATA SOURCES AND STUDY SETTING: In fall 2019, we collected primary survey data with participants in the Appalachian region. STUDY DESIGN: We conducted an online survey including patient-centered measures of contraceptive care and behavior. DATA COLLECTION/EXTRACTION METHODS: We used social media advertisements to recruit Appalachians of reproductive age who were assigned female at birth (N = 622). After exploring the frequency of upward coercion (pressure to use contraception) and downward coercion (pressure not to use contraception), we ran chi-square and logistic regression analyses to explore the relationships between contraceptive coercion and preferred contraceptive use. PRINCIPAL FINDINGS: Approximately one in four (23%, n = 143) participants reported that they were not using their preferred contraceptive method. More than one-third of participants (37.0%, n = 230) reported ever experiencing coercion in their contraceptive care, with 15.8% reporting downward coercion and 29.6% reporting upward coercion. Chi-square tests indicated that downward (χ2 (1) = 23.337, p < 0.001) and upward coercion (χ2 (1) = 24.481, p < 0.001) were both associated with a decreased likelihood of using the preferred contraceptive method. These relationships remained significant when controlling for sociodemographic factors in a logistic regression model (downward coercion: Marginal effect = -0.169, p = 0.001; upward coercion: Marginal effect = -0.121, p = 0.002). CONCLUSIONS: This study utilized novel person-centered measures to investigate contraceptive coercion in the Appalachian region. Findings highlight the negative impact of contraceptive coercion on patients' reproductive autonomy. Promoting contraceptive access, in Appalachia and beyond, requires comprehensive and unbiased contraceptive care.
Assuntos
Coerção , Anticoncepcionais , Recém-Nascido , Humanos , Feminino , Estados Unidos , Anticoncepção , Acessibilidade aos Serviços de Saúde , Região dos ApalachesRESUMO
OBJECTIVE: To document physicians' beliefs about abortion safety and the associations between these beliefs and physician support for, referral for, and participation in abortion care. METHODS: In a 2019 survey at the University of Wisconsin School of Medicine and Public Health, we assessed physicians' abortion attitudes, beliefs, and practices (N = 893). We conducted bivariate analyses followed by logistic regression to document relationships between physician beliefs about abortion safety and their support for, referral to, and participation in abortion care. RESULTS: Four-in-five physicians (78%, n = 690) believed that abortion is very or extremely safe. Medical specialty (Obstetrics-Gynecology vs. other; adjusted odds ratio [aOR] = 10.58, 95% CI: 1.41-79.56), educational exposure to abortion (aOR = 1.43, 95% CI: 1.02-2.01), and religiosity (aOR = 0.59, 95% CI: 0.41-0.85) were associated with physicians' beliefs about the safety of abortion. Providers who believed that abortion was very/extremely safe were more likely to support medication (aOR = 2.99, 95% CI: 1.93-4.65) and procedural abortion (aOR = 3.56, 95% CI: 2.31-5.50) and refer patients for abortion care (aOR = 3.14, 95% CI: 1.90-5.01). CONCLUSION: Although abortions are associated with extremely few adverse events, a sizable portion of surveyed physicians had incorrect perceptions of the safety of abortion. These beliefs were associated with decreased support and referrals for abortion care. Educational exposure to abortion is associated with more accurate assessments of abortion safety, underscoring the importance of training in this area. Considering the current abortion policy landscape, it is imperative for physicians to hold accurate knowledge about abortion so they can provide comprehensive counseling and, when indicated, referrals for safe and legal care.
Assuntos
Aborto Induzido , Médicos , Gravidez , Feminino , Humanos , Atitude do Pessoal de Saúde , Inquéritos e Questionários , Encaminhamento e ConsultaRESUMO
Acidification of the cellular lysosome is an important factor in infection of mammalian cells by SARS-CoV-2. Therefore, raising the pH of the lysosome would theoretically be beneficial in prevention or treatment of SARS-CoV-2 infection. Sodium bicarbonate, carbicarb, and THAM are buffers that can be used clinically to provide base to patients. To examine whether these bases could raise lysosomal pH and therefore be a primary or adjunctive treatment of SARS-CoV-2 infection, we measured lysosomal and intracellular pH of mammalian cells after exposure to each of these bases. Mammalian HEK293 cells expressing RpH-LAMP1-3xFLAG, a ratiometric sensor of lysosomal luminal pH, were first exposed to Hepes which was then switched to sodium bicarbonate, carbicarb, or THAM and lysosomal pH measured. In bicarbonate buffer the mean lysosomal pH was 4.3 ± 0.1 (n = 20); p = NS versus Hepes (n = 20). The mean lysosomal pH in bicarbonate/carbonate was 4.3 ± 0.1 (n = 21) versus Hepes (n = 21), p = NS. In THAM buffer the mean lysosomal pH was 4.7 ± 0.07 (n = 20) versus Hepes (4.6 ± 0.1, n = 20), p = NS. In addition, there was no statistical difference between pHi in bicarbonate, carbicarb or THAM solutions. Using the membrane permeable base NH4Cl (5 mM), lysosomal pH increased significantly to 5.9 ± 0.1 (n = 21) compared to Hepes (4.5 ± 0.07, n = 21); p < 0.0001. Similarly, exposure to 1 mM hydroxychloroquine significantly increased the lysosomal pH to (5.9 ± 0.06, n = 20) versus Hepes (4.3 ± 0.1, n = 20), p < 0.0001. Separately steady-state pHi was measured in HEK293 cells bathed in various buffers. In bicarbonate pHi was 7.29 ± 0.02 (n = 12) versus Hepes (7.45 ± 0.03, [n = 12]), p < 0.001. In cells bathed in carbicarb pHi was 7.27 ± 0.02 (n = 5) versus Hepes (7.43 ± 0.04, [n = 5]), p < 0.01. Cells bathed in THAM had a pHi of 7.25 ± 0.03 (n = 12) versus Hepes (7.44 ± 0.03 [n = 12]), p < 0.001. In addition, there was no statistical difference in pHi in bicarbonate, carbicarb or THAM solutions. The results of these studies indicate that none of the buffers designed to provide base to patients alters lysosomal pH at the concentrations used in this study and therefore would be predicted to be of no value in the treatment of SARS-CoV-2 infection. If the goal is to raise lysosomal pH to decrease the infectivity of SARS-CoV-2, utilizing lysosomal permeable buffers at the appropriate dose that is non-toxic appears to be a useful approach to explore.