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1.
Obstet Gynecol ; 141(5): 995-1003, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-37023461

RESUMO

OBJECTIVE: To evaluate how Texas health care professionals who care for patients experiencing medically complex pregnancies navigate abortion restrictions. METHODS: We conducted qualitative in-depth interviews with health care professionals across Texas who cared for patients with life-limiting fetal diagnoses or who had existing or developed health conditions that adversely affected pregnancy. We conducted the first round of interviews March-June 2021 and the second round of interviews January-May 2022 after the implementation of Texas Senate Bill 8 (SB8), which prohibited most abortions after detection of embryonic cardiac activity. We used inductive and deductive qualitative analysis to identify themes and changes in practice after the implementation of SB8. RESULTS: We conducted a total of 50 interviews: 25 before implementation of SB8 and 25 after the law's implementation. We interviewed 21 maternal-fetal medicine specialists, 19 obstetrician-gynecologists, eight physicians whose primary practice is the provision of abortion care, and two genetic counselors. Participants reported presenting their patients with information about health risks and outcomes of continued pregnancy in each policy period; however, counseling on these options was curtailed after implementation of SB8. Even in cases in which a patient's health and, in some cases, life would be compromised, narrow criteria for abortions at hospitals limited care before implementation of SB8, and criteria often became more stringent after implementation of SB8. Administrative approval processes and referrals for abortion delayed care and endangered patients' health, which worsened after in-state options were eliminated after implementation of SB8. Participants noted that patients with more limited resources who were unable to travel out of state often had to continue pregnancies, further increasing their risk of morbidity. CONCLUSION: Texas health care professionals' abilities to provide evidence-based abortion care to patients with medically complex pregnancies were constrained by institutional policies, and care options narrowed further after implementation of SB8. Abortion restrictions limit shared decision making, compromise patient care, and put pregnant people's health at risk.


Assuntos
Aborto Induzido , Acessibilidade aos Serviços de Saúde , Gravidez , Feminino , Humanos , Texas , Aconselhamento , Hospitais
2.
Soc Work ; 68(2): 103-111, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36795036

RESUMO

In the United States, abortion is safe and common, but highly stigmatized and frequently targeted by legislation that aims to restrict access. Numerous obstacles impede access to abortion care, including logistical barriers like cost and transportation, limited clinic availability, and state-mandated waiting periods. Accurate abortion information can also be hard to access. To overcome these barriers, many people seeking abortion turn to anonymous online forums, including Reddit, for information and support. Examining this community provides a unique perspective on the questions, thoughts, and needs of people considering or undergoing an abortion. The authors web scraped 250 posts from subreddits that contain abortion-related posts, then coded deidentified posts using a combined deductive/inductive approach. The authors identified a subset of these codes in which users were giving/seeking information and advice on Reddit, then engaged in a targeted analysis of the needs expressed in these posts. Three interconnected needs emerged: (1) need for information, (2) need for emotional support, and (3) need for community around the abortion experience. In this study map the authors reflected these needs onto key social work practice areas and competencies; taken alongside support from social work's governing bodies, this research suggests that social workers would be beneficial additions to the abortion care workforce.


Assuntos
Aspirantes a Aborto , Aborto Induzido , Gravidez , Feminino , Humanos , Estados Unidos , Serviço Social , Apoio Social , Pesquisa Qualitativa
3.
Contraception ; 118: 109896, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36240904

RESUMO

OBJECTIVES: Political and public health responses to the COVID-19 pandemic changed provision of abortion care and exacerbated existing barriers. We aimed to explore experiences of individuals seeking abortion care in 2 abortion-restrictive states in the United States where state policies and practice changes disrupted abortion provision during the pandemic. STUDY DESIGN: We conducted 22 semistructured interviews in Texas (n = 10) and Ohio (n = 12) to assess how state executive orders limiting abortion, along with other public health guidance and pandemic-related service delivery changes, affected individuals seeking abortion care. We included individuals 18 years and older who contacted a facility for abortion care between March and November 2020. We coded and analyzed interview transcripts using both inductive and deductive approaches. RESULTS: Participants reported obstacles to obtaining their preferred timing and method of abortion. These obstacles placed greater demands on those seeking abortion and resulted in delays in obtaining care for as long as 11 weeks, as well as some being unable to obtain an abortion at all. CONCLUSIONS: Political and public health responses to the COVID-19 pandemic - exacerbated pre-pandemic barriers and existing restrictions and constrained options for people seeking abortion in Ohio and Texas. Delays were consequential for all participants, regardless of their ultimate ability to obtain an abortion. IMPLICATIONS: During the COVID-19 pandemic, state executive orders and clinic practices exacerbated already constrained access to care. Findings highlight the importance of protecting timely care and the full range of abortion methods. Findings also preview barriers individuals seeking abortion may encounter in states that restrict or ban abortion.


Assuntos
Aborto Induzido , COVID-19 , Gravidez , Feminino , Estados Unidos , Humanos , Texas , Pandemias , Acessibilidade aos Serviços de Saúde , Ohio
4.
Womens Health Issues ; 33(3): 228-234, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36535886

RESUMO

INTRODUCTION: After the onset of the COVID-19 pandemic, the use of family planning services decreased, but there are limited data on how safety net providers were affected. METHODS: Between November 2020 and March 2021, we conducted in-depth interviews with administrators at health departments, federally qualified health centers, and specialized family planning organizations across Texas about pandemic-related changes in family planning services. We analyzed interview transcripts using an inductive thematic approach. RESULTS: Administrators at the 19 participating organizations described pervasive service disruptions. Some organizations closed for 6-8 weeks at the pandemic's onset owing to safety uncertainties and difficulty interpreting Texas' March 2020 executive order prohibiting "nonessential" medical services; others later suspended services after staff exposures. Health departments and federally qualified health centers commonly decreased family planning services to focus on COVID-19 response, leaving specialized family planning organizations to absorb displaced reproductive health care clients. Some of the advantages of service delivery modifications-including telehealth, curbside and drive-through prescription pickup, and medication by mail-were difficult to realize; barriers included low reimbursement, necessary patient examinations, and clients' confidentiality concerns and lack of technological resources. CONCLUSIONS: Texas' diverse network of family planning organizations illustrated a range of responses to the pandemic, and organizations often focused on their core missions-public health, primary care, or family planning.


Assuntos
COVID-19 , Serviços de Planejamento Familiar , Humanos , Texas/epidemiologia , Pandemias , COVID-19/epidemiologia , Pessoal Administrativo
5.
Support Care Cancer ; 30(12): 10441-10452, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36214878

RESUMO

PURPOSE: The American Society of Clinical Oncology Clinical Practice guidelines recommend that non-physicians such as nurses, social workers, and psychologists should be prepared to discuss fertility and sexual concerns with patients. However, literature showed that the utilization rate of sexual and reproductive care for women with cancer remained low. We conducted a scoping review to describe non-physicians' roles, barriers, and facilitators providing sexual and reproductive health (SRH) care to women of reproductive age with cancer. METHODS: We searched six databases for articles that met the following criteria: (1) English language; (2) original research; (3) non-physician providers; (4) women with cancer under age 50. We categorized barriers and facilitators at the system-, individual-, and clinical encounter-levels from providers' and patients' perspectives. RESULTS: We included 27 studies from 3451 retrieved articles. The majority of studies have a focus on fertility preservation or sexuality (n = 25). At the system level, the main barriers for non-physicians were lack of SRH care guidelines and collaborating experts. Concerns for patients included socioeconomic and geographic constraints in obtaining care. At the encounter level, providers and patients lacked experience discussing SRH. At the individual level, providers' lack of knowledge in SRH treatment options and interprofessional collaboration and patients' lack of awareness about treatment effects hindered SRH discussions. Facilitators include the availability of SRH programs and specialists, and rapport between providers and patients. CONCLUSIONS: Supporting non-physicians to provide SRH services to women with cancer requires investment in clinical guidelines, interprofessional collaboration, and training in patient communication.


Assuntos
Neoplasias , Saúde Sexual , Humanos , Feminino , Pessoa de Meia-Idade , Saúde Reprodutiva , Comportamento Sexual , Fertilidade , Neoplasias/terapia
6.
Front Immunol ; 13: 873560, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693814

RESUMO

Regulatory T cell (Treg) adoptive cell therapy (ACT) represents an emerging strategy for restoring immune tolerance in autoimmune diseases. Tregs are commonly purified using a CD4+CD25+CD127lo/- gating strategy, which yields a mixed population: 1) cells expressing the transcription factors, FOXP3 and Helios, that canonically define lineage stable thymic Tregs and 2) unstable FOXP3+Helios- Tregs. Our prior work identified the autoimmune disease risk-associated locus and costimulatory molecule, CD226, as being highly expressed not only on effector T cells but also, interferon-γ (IFN-γ) producing peripheral Tregs (pTreg). Thus, we sought to determine whether isolating Tregs with a CD4+CD25+CD226- strategy yields a population with increased purity and suppressive capacity relative to CD4+CD25+CD127lo/- cells. After 14d of culture, expanded CD4+CD25+CD226- cells displayed a decreased proportion of pTregs relative to CD4+CD25+CD127lo/- cells, as measured by FOXP3+Helios- expression and the epigenetic signature at the FOXP3 Treg-specific demethylated region (TSDR). Furthermore, CD226- Tregs exhibited decreased production of the effector cytokines, IFN-γ, TNF, and IL-17A, along with increased expression of the immunoregulatory cytokine, TGF-ß1. Lastly, CD226- Tregs demonstrated increased in vitro suppressive capacity as compared to their CD127lo/- counterparts. These data suggest that the exclusion of CD226-expressing cells during Treg sorting yields a population with increased purity, lineage stability, and suppressive capabilities, which may benefit Treg ACT for the treatment of autoimmune diseases.


Assuntos
Doenças Autoimunes , Fatores de Transcrição Forkhead , Terapia Baseada em Transplante de Células e Tecidos , Citocinas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Humanos , Interferon gama , Linfócitos T Reguladores
7.
Nature ; 603(7899): 166-173, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35197630

RESUMO

Combinations of anti-cancer drugs can overcome resistance and provide new treatments1,2. The number of possible drug combinations vastly exceeds what could be tested clinically. Efforts to systematically identify active combinations and the tissues and molecular contexts in which they are most effective could accelerate the development of combination treatments. Here we evaluate the potency and efficacy of 2,025 clinically relevant two-drug combinations, generating a dataset encompassing 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines. We show that synergy between drugs is rare and highly context-dependent, and that combinations of targeted agents are most likely to be synergistic. We incorporate multi-omic molecular features to identify combination biomarkers and specify synergistic drug combinations and their active contexts, including in basal-like breast cancer, and microsatellite-stable or KRAS-mutant colon cancer. Our results show that irinotecan and CHEK1 inhibition have synergistic effects in microsatellite-stable or KRAS-TP53 double-mutant colon cancer cells, leading to apoptosis and suppression of tumour xenograft growth. This study identifies clinically relevant effective drug combinations in distinct molecular subpopulations and is a resource to guide rational efforts to develop combinatorial drug treatments.


Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Pancreáticas , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética
8.
Cell Chem Biol ; 29(2): 191-201.e8, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34348113

RESUMO

We identify the Plasmodium falciparum acetyl-coenzyme A synthetase (PfAcAS) as a druggable target, using genetic and chemical validation. In vitro evolution of resistance with two antiplasmodial drug-like compounds (MMV019721 and MMV084978) selects for mutations in PfAcAS. Metabolic profiling of compound-treated parasites reveals changes in acetyl-CoA levels for both compounds. Genome editing confirms that mutations in PfAcAS are sufficient to confer resistance. Knockdown studies demonstrate that PfAcAS is essential for asexual growth, and partial knockdown induces hypersensitivity to both compounds. In vitro biochemical assays using recombinantly expressed PfAcAS validates that MMV019721 and MMV084978 directly inhibit the enzyme by preventing CoA and acetate binding, respectively. Immunolocalization studies reveal that PfAcAS is primarily localized to the nucleus. Functional studies demonstrate inhibition of histone acetylation in compound-treated wild-type, but not in resistant parasites. Our findings identify and validate PfAcAS as an essential, druggable target involved in the epigenetic regulation of gene expression.


Assuntos
Acetato-CoA Ligase/antagonistas & inibidores , Antimaláricos/farmacologia , Inibidores Enzimáticos/farmacologia , Malária/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Acetato-CoA Ligase/metabolismo , Antimaláricos/química , Inibidores Enzimáticos/química , Humanos , Malária/metabolismo , Modelos Moleculares , Estrutura Molecular , Testes de Sensibilidade Parasitária , Plasmodium falciparum/enzimologia
9.
Artigo em Inglês | MEDLINE | ID: mdl-34501602

RESUMO

OBJECTIVE: The Hyde Amendment and related policies limit or prohibit Medicaid coverage of abortion services in the United States. Most research on cost-related abortion barriers relies on clinic-based samples, but people who desire abortions may never make it to a healthcare center. To examine a novel, pre-abortion population, we analyzed a unique qualitative dataset of posts from Reddit, a widely used social media platform increasingly leveraged by researchers, to assess financial obstacles among anonymous posters considering abortion. METHODS: In February 2020, we used Python to web-scrape the 250 most recent posts that mentioned abortion, removing all identifying information and usernames. After transferring all posts into NVivo, a qualitative software package, the team identified all datapoints related to cost. Three qualitatively trained evaluators established and applied codes, reaching saturation after 194 posts. The research team used a descriptive qualitative approach, using both inductive and deductive elements, to identify and analyze themes related to financial barriers. RESULTS: We documented multiple cost-related deterrents, including lack of funds for both the procedure and attendant travel costs, inability to afford desired abortion modality (i.e., medication or surgical), and for some, consideration of self-managed abortion options due to cost barriers. CONCLUSIONS: Findings from this study underscore the centrality of cost barriers and third-party payer restrictions to stymying reproductive health access in the United States. Results may contribute to the growing evidence base and building political momentum focused on repealing the Hyde Amendment.


Assuntos
Aspirantes a Aborto , Aborto Induzido , Aborto Legal , Atenção à Saúde , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Medicaid , Gravidez , Estados Unidos
10.
Womens Health Issues ; 31(5): 478-484, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34238669

RESUMO

BACKGROUND: The LGBTQ health disparities literature documents barriers to comprehensive and queer-inclusive care. Queer cisgender women and gender expansive individuals assigned female at birth experience myriad health disparities related to reproductive health, in part owing to the health care system. However, few studies have examined how queer individuals cope with and overcome barriers to queer-competent reproductive health care. This study aims to understand the strategies queer cisgender women and gender expansive individuals use to meet their reproductive health needs. METHODS: Investigators conducted interviews with 22 queer cisgender women and gender expansive individuals assigned female at birth about their experiences seeking reproductive health care services. We used inductive coding and thematic analysis to identify themes related to meeting reproductive health and health care needs. RESULTS: Findings highlight the prevalence of negative and harmful experiences while seeking reproductive health care. In response to these negative experiences, individuals developed active strategies to meet their health needs, including seeking information and community, seeking alternative models of care, and managing identity disclosure. Importantly, these strategies varied in effectiveness, depending on participants' social and economic advantage. CONCLUSIONS: Queer individuals face numerous barriers to queer-competent reproductive health care when seeking reproductive health services. While queer patients are often resilient and creative, developing strategies to get their needs met, the presence of such strategies highlights the need for structural changes in the health system to better serve queer patients.


Assuntos
Saúde Reprodutiva , Minorias Sexuais e de Gênero , Feminino , Identidade de Gênero , Humanos , Recém-Nascido
11.
Infant Ment Health J ; 42(3): 386-399, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955042

RESUMO

Supportive father involvement during pregnancy can positively impact maternal and child outcomes. Father participation in prenatal care is increasing, yet little research exists to understand how mothers and fathers experience father participation in prenatal care and their preferences for father participation. We interviewed expectant first-time mothers (N = 22) and fathers (N = 20) to learn about fathers' participation in prenatal care, perceptions of providers' treatment of fathers, and preferences for father participation. Interviews were coded using principles of grounded theory. Father participation ranged from attendance at visits considered "important" (e.g., ultrasounds) to attendance at every appointment. Experiences of father participation varied, with many describing it as both an important act of support for the mother and part of assuming the role of father. Most participants saw great value in father participation in prenatal care as an opportunity for fathers to learn how to support a healthy pregnancy, bond with their developing baby, and share joy and/or worries with mothers. Participants generally felt that fathers were made to feel welcome and wanted providers to be inclusive of fathers during appointments. Results of this study suggest that father participation presents an opportunity for prenatal care providers to foster fathers' positive involvement in pregnancy, support for mothers, and preparation to parent.


El apoyo participativo del papá durante el embarazo puede tener un impacto positivo en el resultado materno y del niño. La participación del papá en el cuidado prenatal está aumentando, sin embargo, existe poca investigación para comprender cómo las mamás y los papás experimentan la participación del papá en el cuidado prenatal, y sus preferencias en cuanto a la participación del papá. Entrevistamos a madres primerizas embarazadas (N = 22) y papás (N = 20) para conocer acerca de la participación de los papás en el cuidado prenatal, las percepciones que acerca de los papás tenían quienes ofrecen el tratamiento, así como las preferencias en cuanto a la participación del papá. Se codificaron las entrevistas usando principios de teoría fundamentada. La participación del papá osciló desde el asistir a visitas consideradas "importantes" (v.g. el ultrasonido) hasta el asistir a cada cita. Las experiencias de la participación del papá variaron, y muchos las describieron como un acto importante de apoyo para la mamá y parte de asumir el papel de papá. La mayoría de los participantes vio un gran valor en la participación del papá en el cuidado prenatal, así como una oportunidad para los papás de aprender cómo prestar apoyo a un embarazo sano, establecer una relación con su bebé en desarrollo y compartir las alegrías y/o las preocupaciones con las mamás. Los participantes generalmente sintieron que a los papás se les hizo sentir bienvenidos y querían que quienes prestaban el cuidado incluyeran a los papás durante la cita. Los resultados de este estudio sugieren que la participación del papá presenta una oportunidad para quienes prestan el cuidado prenatal de fomentar una participación positiva en el embarazo, el apoyo a las mamás y la preparación para ser padre.


La participation d'appui du père durant la grossesse peut affecter de manière positive les résultats maternels et l'enfant. La participation du père au soin prénatal augmente et cependant il existe peu de recherches permettant de comprendre comment les mères et les pères font l'expérience de la participation du père au soin prénatal et leurs préférences pour la participation du père. Nous avons interviewé des mères attendant leur premier enfant (N = 22) et des pères (N = 20) afin de découvrir la participation des pères au soin prénatal, les perceptions de manière dont les prestataires traitent les pères, et les préférences pour ce qui concerne la participation des pères. Les entretiens ont été codés en utilisant les principes de théorie ancrée. La participation du père est allée de la présence aux visites considérées comme étant "importantes" (comme par exemple les ultrasons) à la présence à chaque rendez-vous. Les expériences de la participation des pères ont varié, la plupart des participants la décrivant comme étant à la fois un acte de soutien important pour la mère et une partie du fait d'assumer le rôle de père. La plupart des participants ont ressenti une grande valeur en la participation du père dans le soin prénatal, en la considérant comme une chance pour les pères d'apprendre comment soutenir une grossesse saine, de se lier avec leur bébé se développant et de partager la joie et/ou les inquiétudes avec les mères. Les participants ont généralement ressenti que les pères étaient bien accueillis et souhaitaient que les prestataires incluent les pères durant les rendez-vous. Les résultats de cette étude suggèrent que la participation du père présente une opportunité pour les prestataires de soin prénatal de cultiver une participation positive des pères à la grossesse, au soin des mères et à la préparation au parentage.


Assuntos
Pai , Mães , Ansiedade , Criança , Feminino , Humanos , Masculino , Gravidez , Cuidado Pré-Natal
13.
ACS Infect Dis ; 7(4): 811-825, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33715347

RESUMO

In malaria, chemical genetics is a powerful method for assigning function to uncharacterized genes. MMV085203 and GNF-Pf-3600 are two structurally related napthoquinone phenotypic screening hits that kill both blood- and sexual-stage P. falciparum parasites in the low nanomolar to low micromolar range. In order to understand their mechanism of action, parasites from two different genetic backgrounds were exposed to sublethal concentrations of MMV085203 and GNF-Pf-3600 until resistance emerged. Whole genome sequencing revealed all 17 resistant clones acquired nonsynonymous mutations in the gene encoding the orphan apicomplexan transporter PF3D7_0312500 (pfmfr3) predicted to encode a member of the major facilitator superfamily (MFS). Disruption of pfmfr3 and testing against a panel of antimalarial compounds showed decreased sensitivity to MMV085203 and GNF-Pf-3600 as well as other compounds that have a mitochondrial mechanism of action. In contrast, mutations in pfmfr3 provided no protection against compounds that act in the food vacuole or the cytosol. A dihydroorotate dehydrogenase rescue assay using transgenic parasite lines, however, indicated a different mechanism of action for both MMV085203 and GNF-Pf-3600 than the direct inhibition of cytochrome bc1. Green fluorescent protein (GFP) tagging of PfMFR3 revealed that it localizes to the parasite mitochondrion. Our data are consistent with PfMFR3 playing roles in mitochondrial transport as well as drug resistance for clinically relevant antimalarials that target the mitochondria. Furthermore, given that pfmfr3 is naturally polymorphic, naturally occurring mutations may lead to differential sensitivity to clinically relevant compounds such as atovaquone.


Assuntos
Antimaláricos , Malária , Antimaláricos/farmacologia , Resistência a Medicamentos , Humanos , Malária/tratamento farmacológico , Mutação , Plasmodium falciparum/genética
14.
mBio ; 11(6)2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293381

RESUMO

Plasmodium parasites rely heavily on glycolysis for ATP production and for precursors for essential anabolic pathways, such as the methylerythritol phosphate (MEP) pathway. Here, we show that mutations in the Plasmodium falciparum glycolytic enzyme, phosphofructokinase (PfPFK9), are associated with in vitro resistance to a primary sulfonamide glycoside (PS-3). Flux through the upper glycolysis pathway was significantly reduced in PS-3-resistant parasites, which was associated with reduced ATP levels but increased flux into the pentose phosphate pathway. PS-3 may directly or indirectly target enzymes in these pathways, as PS-3-treated parasites had elevated levels of glycolytic and tricarboxylic acid (TCA) cycle intermediates. PS-3 resistance also led to reduced MEP pathway intermediates, and PS-3-resistant parasites were hypersensitive to the MEP pathway inhibitor, fosmidomycin. Overall, this study suggests that PS-3 disrupts core pathways in central carbon metabolism, which is compensated for by mutations in PfPFK9, highlighting a novel metabolic drug resistance mechanism in P. falciparumIMPORTANCE Malaria, caused by Plasmodium parasites, continues to be a devastating global health issue, causing 405,000 deaths and 228 million cases in 2018. Understanding key metabolic processes in malaria parasites is critical to the development of new drugs to combat this major infectious disease. The Plasmodium glycolytic pathway is essential to the malaria parasite, providing energy for growth and replication and supplying important biomolecules for other essential Plasmodium anabolic pathways. Despite this overreliance on glycolysis, no current drugs target glycolysis, and there is a paucity of information on critical glycolysis targets. Our work addresses this unmet need, providing new mechanistic insights into this key pathway.


Assuntos
Antimaláricos/farmacologia , Glicosídeos/farmacologia , Fosfofrutoquinases/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/enzimologia , Alelos , Antimaláricos/química , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Glicólise , Glicosídeos/química , Metabolômica/métodos , Modelos Moleculares , Estrutura Molecular , Testes de Sensibilidade Parasitária , Fosfofrutoquinases/genética , Plasmodium falciparum/genética , Polimorfismo de Nucleotídeo Único , Conformação Proteica , Relação Estrutura-Atividade
15.
Soc Work ; 65(4): 358-367, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33020834

RESUMO

Reproductive justice is an intersectional social movement, theory, and praxis well aligned with social work's mission and values. Yet, advancing reproductive justice-the right to have children, to not have children, to parent with safety and dignity, and to sexual and bodily autonomy-has not been a signature area of scholarship and practice for the field. This article argues that it is critical for social work to advance reproductive justice to truly achieve the grand challenge of closing the health gap. The article starts by discussing the history and tenets of reproductive justice and how it overlaps with social work ethics. The authors then highlight some of the ways by which social workers have been disruptors of and complicit in the oppression of individuals, families, and communities with regard to their reproductive rights and outcomes. The article concludes with a call to action and recommendations for social work to foreground reproductive justice in research, practice, and education efforts by centering marginalized voices while reimagining the field's pursuit of health equity.


Assuntos
Direitos Sexuais e Reprodutivos , Mudança Social , Justiça Social , Serviço Social/ética , Feminino , Disparidades nos Níveis de Saúde , Humanos , Masculino , Gravidez
16.
Cell Chem Biol ; 27(7): 806-816.e8, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32359426

RESUMO

The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation. Metabolomic, phosphoproteomic, and chemoproteomic studies, validated with conditional knockdown parasites, molecular docking, and recombinant kinase assays, identified cGMP-dependent protein kinase (PKG) as the primary target of MMV030084. PKG is known to play essential roles in Plasmodium invasion of and egress from host cells, matching MMV030084's activity profile. Resistance selections and gene editing identified tyrosine kinase-like protein 3 as a low-level resistance mediator for PKG inhibitors, while PKG itself never mutated under pressure. These studies highlight PKG as a resistance-refractory antimalarial target throughout the Plasmodium life cycle and promote MMV030084 as a promising Plasmodium PKG-targeting chemotype.


Assuntos
Antimaláricos/farmacologia , Proteínas Quinases Dependentes de GMP Cíclico/antagonistas & inibidores , Resistência a Medicamentos/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Proteínas de Protozoários/antagonistas & inibidores , Animais , Antimaláricos/química , Antimaláricos/metabolismo , Sítios de Ligação , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Feminino , Hepatócitos/citologia , Hepatócitos/metabolismo , Hepatócitos/parasitologia , Humanos , Imidazóis/química , Estágios do Ciclo de Vida/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Plasmodium falciparum/crescimento & desenvolvimento , Plasmodium falciparum/metabolismo , Proteômica , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo
17.
Soc Work Health Care ; 59(3): 180-198, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32208846

RESUMO

Sexual minority women (SMW) face both increased risk for unintended pregnancy and barriers to achieving wanted pregnancy, but little research investigates SMW's pregnancy desires. To fill this gap, we conducted five focus groups and 11 in-depth interviews with 20-30-year-old SMW in three US cities. Findings highlight that the heteronormative pregnancy planning paradigm lacks salience for SMW. While some SMW clearly wish to avoid pregnancy, many others are unsure, and factors influencing this uncertainty include relationship context, anticipating logistical barriers, and discord between queer identity and pregnancy.


Assuntos
Serviços de Planejamento Familiar/organização & administração , Gravidez não Planejada/psicologia , Minorias Sexuais e de Gênero/psicologia , Adulto , Feminino , Humanos , Entrevistas como Assunto , Gravidez , Estados Unidos , Adulto Jovem
18.
Am J Public Health ; 109(12): 1680-1686, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31536410

RESUMO

Compared with their heterosexual peers, sexual minority women (SMW; e.g., queer, bisexual, lesbian, pansexual) have an elevated risk for unintended pregnancy.A team of social science and clinical researchers qualitatively documented the multilevel pathways leading to this disparity, particularly the contexts of contraceptive use. From August 2017 to April 2018, we conducted focus groups and interviews with young adult cisgender SMW in 3 cities: Chicago, Illinois; Madison, Wisconsin; and Salt Lake City, Utah.Most participants reported experience with both penile-vaginal intercourse and contraception. However, they faced several queer-specific barriers to preventing unwanted pregnancy, including a comparative lack of self-concept as contraceptive users, fear of stigma from both queer and health care communities, use of less-effective methods because of infrequent penile-vaginal intercourse and a sense that longer-acting methods were "overkill," and previous experiences of discrimination such as homophobia and gender-based violence. However, participants also reported ways that contraception could align with queer identity, including both taking advantage of noncontraceptive benefits and framing contraception as sex- and queer-positive. These facilitators can inform future efforts to help SMW better meet their pregnancy prevention needs.


Assuntos
Comportamento Contraceptivo/psicologia , Gravidez não Planejada/psicologia , Minorias Sexuais e de Gênero/psicologia , Adulto , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Gravidez , Pesquisa Qualitativa , Autoimagem , Estigma Social , Fatores Socioeconômicos , Estados Unidos , Adulto Jovem
19.
Cell Microbiol ; 21(12): e13108, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31454137

RESUMO

The malaria parasite Plasmodium and other apicomplexans such as Toxoplasma evolved from photosynthetic organisms and contain an essential, remnant plastid termed the apicoplast. Transcription of the apicoplast genome is polycistronic with extensive RNA processing. Yet little is known about the mechanism of apicoplast RNA processing. In plants, chloroplast RNA processing is controlled by multiple pentatricopeptide repeat (PPR) proteins. Here, we identify the single apicoplast PPR protein, PPR1. We show that the protein is essential and that it binds to RNA motifs corresponding with previously characterized processing sites. Additionally, PPR1 shields RNA transcripts from ribonuclease degradation. This is the first characterization of a PPR protein from a nonphotosynthetic plastid.


Assuntos
Apicoplastos/genética , Cloroplastos/genética , Filogenia , Plasmodium falciparum/genética , Toxoplasma/genética
20.
Obstet Gynecol ; 133(5): 1012-1023, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30969215

RESUMO

OBJECTIVE: To describe a group of young sexual minority women's experiences with and preferences for sexual identity disclosure in the context of contraceptive care. METHODS: In Chicago, Illinois, Salt Lake City, Utah, and Madison, Wisconsin, investigators conducted five focus groups (n=22) and 11 interviews with women aged 20-30 years who identified as something other than heterosexual. Focus groups explored social norms regarding contraceptive care; interviews documented individual experiences with contraceptive care. Using a qualitative descriptive approach and combined deductive and inductive content analysis, investigators coded transcripts for themes related to disclosing sexual orientation to contraceptive providers. RESULTS: Participants described the process of sexual identity disclosure in contraceptive care in three stages: 1) listening for whether, when, and how health care providers asked about sexual orientation, 2) deciding whether or not to disclose sexual identity to providers, and 3) evaluating responses from providers after disclosure. Participants wanted providers to: avoid assumptions and ask about both sexual identity and sexual behaviors, signal their openness and competence around the health of sexual minority women during contraceptive encounters, and focus discussions on the individual patient's priorities and needs for contraceptive care. CONCLUSION: Decisions made by sexual minority women about sexual identity disclosure in contraceptive contexts are influenced by previous and current interactions with health care providers. Contraceptive providers should ask all patients about sexual identity and sexual behavior, avoid assumptions about use of and need for contraception, and acknowledge the prevalence of marginalization, discrimination, and stigma experienced by sexual minority women and their communities in health care contexts.


Assuntos
Revelação , Identidade de Gênero , Pessoal de Saúde/psicologia , Minorias Sexuais e de Gênero/psicologia , Estigma Social , Adulto , Anticoncepção , Feminino , Grupos Focais , Humanos , Entrevistas como Assunto , Estados Unidos , Adulto Jovem
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