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1.
PLoS Genet ; 19(5): e1010772, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37228112

RESUMO

Molecular chaperones play a key role in maintaining proteostasis and cellular health. The abundant, essential, cytosolic Hsp90 (Heat shock protein, 90 kDa) facilitates the folding and activation of hundreds of newly synthesized or misfolded client proteins in an ATP-dependent folding pathway. In a simplified model, Hsp70 first helps load client onto Hsp90, ATP binding results in conformational changes in Hsp90 that result in the closed complex, and then less defined events result in nucleotide hydrolysis, client release and return to the open state. Cochaperones bind and assist Hsp90 during this process. We previously identified a series of yeast Hsp90 mutants that appear to disrupt either the 'loading', 'closing' or 'reopening' events, and showed that the mutants had differing effects on activity of some clients. Here we used those mutants to dissect Hsp90 and cochaperone interactions. Overexpression or deletion of HCH1 had dramatically opposing effects on the growth of cells expressing different mutants, with a phenotypic shift coinciding with formation of the closed conformation. Hch1 appears to destabilize Hsp90-nucleotide interaction, hindering formation of the closed conformation, whereas Cpr6 counters the effects of Hch1 by stabilizing the closed conformation. Hch1 and the homologous Aha1 share some functions, but the role of Hch1 in inhibiting progression through the early stages of the folding cycle is unique. Sensitivity to the Hsp90 inhibitor NVP-AUY922 also correlates with the conformational cycle, with mutants defective in the loading phase being most sensitive and those defective in the reopening phase being most resistant to the drug. Overall, our results indicate that the timing of transition into and out of the closed conformation is tightly regulated by cochaperones. Further analysis will help elucidate additional steps required for progression through the Hsp90 folding cycle and may lead to new strategies for modulating Hsp90 function.


Assuntos
Proteínas de Saccharomyces cerevisiae , Humanos , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Choque Térmico HSP90/genética , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/metabolismo , Trifosfato de Adenosina/genética , Trifosfato de Adenosina/metabolismo , Nucleotídeos/metabolismo , Ligação Proteica
2.
J Biol Chem ; 298(5): 101930, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35421375

RESUMO

Immune checkpoint blockade therapy is perhaps the most important development in cancer treatment in recent memory. It is based on decades of investigation into the biology of immune cells and the role of the immune system in controlling cancer growth. While the molecular circuitry that governs the immune system in general-and antitumor immunity in particular-is intensely studied, far less attention has been paid to the role of cellular stress in this process. Proteostasis, intimately linked to cell stress responses, refers to the dynamic regulation of the cellular proteome and is maintained through a complex network of systems that govern the synthesis, folding, and degradation of proteins in the cell. Disruption of these systems can result in the loss of protein function, altered protein function, the formation of toxic aggregates, or pathologies associated with cell stress. However, the importance of proteostasis extends beyond its role in maintaining proper protein function; proteostasis governs how tolerant cells may be to mutations in protein-coding genes and the overall half-life of proteins. Such gene expression changes may be associated with human diseases including neurodegenerative diseases, metabolic disease, and cancer and manifest at the protein level against the backdrop of the proteostasis network in any given cellular environment. In this review, we focus on the role of proteostasis in regulating immune responses against cancer as well the role of proteostasis in determining immunogenicity of cancer cells.


Assuntos
Neoplasias , Proteostase , Humanos , Neoplasias/imunologia , Dobramento de Proteína , Proteoma/metabolismo , Proteostase/imunologia , Deficiências na Proteostase/metabolismo
3.
Am J Perinatol ; 39(13): 1375-1382, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35292948

RESUMO

OBJECTIVE: The objective of this study was to assess the efficacy of an enhanced recovery after surgery (ERAS) protocol and determine its effect on racial/ethnic disparities in postcesarean pain management. STUDY DESIGN: We performed an institutional review board-approved retrospective cohort study of scheduled cesarean deliveries before and after ERAS implementation at a single urban academic institution. Pre-ERAS, all analgesic medications were given postoperatively on patient request. The ERAS protocol included preoperative acetaminophen and celecoxib. Postoperatively, patients received scheduled nonsteroidal anti-inflammatory drugs and acetaminophen. Oral oxycodone was available as needed, and opioid patient-controlled analgesia was eliminated from the standard order set. The primary outcome was total opioid use in the first 48 hours after cesarean, pre- and post-ERAS, reported in total milliequivalents of intravenous morphine (MME). A secondary analysis of opioid use and pain scores by racial groups was also performed. Chi-square, independent t-tests, analysis of variance, Mann-Whitney U, and Kruskal-Wallis tests were used depending on variable and data normality. RESULTS: Pre-ERAS and post-ERAS groups included 100 women each. Post-ERAS, total opioid use in 48 hours was less (40.8 vs. 8.6 MME, p < 0.001) and visual analog scale (VAS) pain scores were lower on postoperative day 1 (POD1) and 2 (POD2) (POD1 maximum at rest: 6.7 vs. 5.3, p < 0.001). Pre-ERAS pain scores differed by race with non-Hispanic Black (NHB) patients reporting the highest mean and max VAS pain scores POD1 and POD2 (POD1, maximum VAS at rest: NHB-7.4, non-Hispanic White-6.6, Hispanic-5.8, Asian-4.4, p = 0.006). Post-ERAS, there were no differences in postoperative pain scores between groups with movement on POD1 and POD2. CONCLUSION: A standardized ERAS protocol for postcesarean pain decreases opioid use and may improve some racial disparities in postcesarean pain control. KEY POINTS: · ERAS protocols improve postoperative pain control and lower postoperative opioid use.. · Studies show that there are racial and ethnic disparities in postpartum pain control.. · Protocols standardize care and may decrease the effects of provider implicit bias..


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Transtornos Relacionados ao Uso de Opioides , Acetaminofen/uso terapêutico , Analgésicos , Analgésicos Opioides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Celecoxib/uso terapêutico , Endrin/análogos & derivados , Feminino , Humanos , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Oxicodona/uso terapêutico , Manejo da Dor/métodos , Dor Pós-Operatória/tratamento farmacológico , Gravidez , Estudos Retrospectivos
4.
J Obstet Gynaecol Res ; 47(2): 501-507, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33145878

RESUMO

AIM: The intrauterine device (IUD) is highly effective birth control, but US IUD usage lags. Barriers to usage, including patient attitudes and lack of knowledge, are not well-characterized. This study sought to investigate how attitudes and knowledge about IUD vary by age and race. METHODS: A survey was distributed to all women in the outpatient obstetrics and gynecology office of a large, urban, academic medical center in Philadelphia. Exclusion criteria included inability to read English or age less than 14 years. Surveys queried participant demographics, knowledge about and opinions of IUD. The authors performed exploratory bi-variable analysis using t tests and chi-square testing to determine which outcomes differed by age and race. For those differing significantly, the authors performed regression analysis to assess for confounding by other factors. RESULTS: Of 1366 women approached, 521 completed the survey (38% response rate). After controlling for confounding, only responses to the statement 'Hormonal birth control is safe and effective' differed significantly by age. Knowledge about IUD did not differ significantly by race, but black women were significantly more likely to perceive that they had insufficient knowledge about IUD compared to white women (odds ratio [OR]: 1.91; 95% confidence interval [CI]: 1.06-3.46). Black women had a more negative opinion of IUD safety (OR: 5.0; 95% CI: 2.35-10.66) and reliability (OR: 5.5; 95% CI: 2.20-14.13) than white women. CONCLUSION: Attitudes and knowledge about IUD do not differ significantly by age. While knowledge about IUD is similar between races, black women may have more negative opinions of IUD.


Assuntos
Ginecologia , Dispositivos Intrauterinos , Adolescente , Anticoncepção , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Gravidez , Reprodutibilidade dos Testes
5.
Biol Chem ; 401(4): 423-434, 2020 03 26.
Artigo em Inglês | MEDLINE | ID: mdl-31782942

RESUMO

Heat shock protein 90 (Hsp90) is a dimeric molecular chaperone that plays an essential role in cellular homeostasis. It functions in the context of a structurally dynamic ATP-dependent cycle to promote conformational changes in its clientele to aid stability, maturation, and activation. The client activation cycle is tightly regulated by a cohort of co-chaperone proteins that display specific binding preferences for certain conformations of Hsp90, guiding Hsp90 through its functional ATPase cycle. Aha-type co-chaperones are well-known to robustly stimulate the ATPase activity of Hsp90 but other roles in regulating the functional cycle are being revealed. In this review, we summarize the work done on the Aha-type co-chaperones since the 1990s and highlight recent discoveries with respect to the complexity of Hsp90 cycle regulation.


Assuntos
Adenosina Trifosfatases/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Chaperonas Moleculares/metabolismo , Adenosina Trifosfatases/química , Proteínas de Choque Térmico HSP90/química , Humanos , Chaperonas Moleculares/química , Ligação Proteica
6.
J Obstet Gynaecol ; 39(2): 164-169, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30230392

RESUMO

Inter-hospital transfers for consultation are common and costly in the USA. Our objective was to evaluate the inter-hospital transfers between the emergency departments (ED) for a gynaecology consultation and to identify markers for potentially avoidable transfers. We performed a retrospective chart review of all transfers accepted by a tertiary care hospital gynaecology service via the ED over two years. Our primary outcome was the designation of the transfer as 'potentially avoidable', defined as a patient discharged home directly from the ED, with no workup or treatment prior to their discharge. The Chi-square tests were used to assess what patient characteristics and medical diagnoses are associated with potentially avoidable transfers. Of 156 patients meeting the inclusion criteria, a total of 38 (24.4%) were potentially avoidable transfers. Women with potentially avoidable transfers were more likely to be pregnant than those whose transfers were necessary (63.2% vs. 40.7% p = .02), and more likely to specifically have a pregnancy of unknown location (PUL) or a complete abortion (p < .01).


Assuntos
Ginecologia/estatística & dados numéricos , Transferência de Pacientes/estatística & dados numéricos , Centros de Atenção Terciária/estatística & dados numéricos , Adulto , Feminino , Humanos , Gravidez , Estudos Retrospectivos
7.
Dev Biol ; 425(1): 58-69, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28322734

RESUMO

The Drosophila vestigial gene is required for proliferation and differentiation of the adult wing and for differentiation of larval and adult muscle identity. Vestigial is part of a multi-protein transcription factor complex, which includes Scalloped, a TEAD-class DNA binding protein. Binding Scalloped is necessary for translocation of Vestigial into the nucleus. We show that Vestigial is extensively post-translationally modified and at least one of these modifications is required for proper function during development. We have shown that there is p38-dependent phosphorylation of Serine 215 in the carboxyl-terminal region of Vestigial. Phosphorylation of Serine 215 occurs in the nucleus and requires the presence of Scalloped. Comparison of a phosphomimetic and non-phosphorylatable mutant forms of Vestigial shows differences in the ability to rescue the wing and muscle phenotypes associated with a null vestigial allele.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Animais Geneticamente Modificados , Linhagem Celular , Núcleo Celular/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/embriologia , Drosophila melanogaster/crescimento & desenvolvimento , Immunoblotting , Microscopia Confocal , Proteína Quinase 11 Ativada por Mitógeno/metabolismo , Músculos/embriologia , Músculos/metabolismo , Mutação , Proteínas Nucleares/metabolismo , Fosforilação , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Serina/genética , Serina/metabolismo , Fatores de Transcrição/metabolismo , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo
8.
Am J Perinatol ; 35(10): 1006-1011, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29510425

RESUMO

OBJECTIVE: To evaluate whether the use of a peanut ball device shortens the duration of active labor in nulliparas. STUDY DESIGN: Single-site, nonblinded randomized trial in nulliparous women admitted for labor or labor induction. English-speaking women > 18 years of age with singleton pregnancies were enrolled. Participants were randomized to the use of peanut ball or usual care upon reaching the active phase of labor (≥ 6 cm cervical dilation) with an epidural. Primary outcome was rate of cervical dilation. Secondary outcomes were rates of cesarean delivery and fetal presentation at time of full dilation or delivery. RESULTS: Ninety-six patients enrolled; 63 reached full cervical dilation. There was no statistically significant difference in rates of cervical dilation (0.98cm/h vs. 0.79cm/h, p = 0.27) or length of labor (315 minutes vs. 387 minutes, p = 0.14) between the groups. There was no difference in the rates of cesarean delivery (33% vs. 35%, p = 0.8) or occiput posterior presentation. (28% vs. 9%, p = 0.09). Among the subgroup who had labor arrest, fewer patients using the peanut ball experienced arrest of dilation; this approached but did not reach statistical significance (30% vs. 73% p = 0.05). CONCLUSION: Use of the peanut ball does not significantly increase rates of cervical dilation or decrease time in active labor.


Assuntos
Cesárea/estatística & dados numéricos , Trabalho de Parto , Complicações do Trabalho de Parto/diagnóstico , Posicionamento do Paciente/instrumentação , Adulto , Feminino , Humanos , Primeira Fase do Trabalho de Parto , Segunda Fase do Trabalho de Parto , Trabalho de Parto Induzido , Paridade , Posicionamento do Paciente/métodos , Philadelphia , Gravidez , Fatores de Tempo , Adulto Jovem
9.
Health Care Women Int ; 38(3): 222-237, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27824305

RESUMO

Most studies on the impact of restrictive abortion laws have focused on patient-level outcomes. To better understand how such laws affect providers, we conducted a qualitative study of 27 abortion providers working under a restrictive law in North Carolina. Providers derived professional identity from their motivations, values, and experiences of pride related to abortion provision. The law affected their professional identities by perpetuating negative characterizations of their profession, requiring changes to patient care and communication, and creating conflicts between professional values and legal obligations. We conclude that a holistic understanding of the impact of abortion laws should include providers' perspectives.


Assuntos
Aborto Induzido/legislação & jurisprudência , Atitude do Pessoal de Saúde , Pessoal de Saúde/psicologia , Legislação Médica , Aborto Induzido/ética , Adulto , Serviços de Planejamento Familiar/métodos , Feminino , Humanos , Entrevistas como Assunto , Legislação como Assunto , Pessoa de Meia-Idade , Motivação , North Carolina , Gravidez , Pesquisa Qualitativa , Direitos da Mulher
10.
Hastings Cent Rep ; 46(2): 22-30, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27120281

RESUMO

Much of the debate on conscience has addressed the ethics of refusal: the rights of providers to refuse to perform procedures to which they object and the interests of the patients who might be harmed by their refusals. But conscience can also be a positive force, grounding decision about offering care.


Assuntos
Aborto Induzido , Consciência , Obrigações Morais , Direitos do Paciente , Relações Médico-Paciente/ética , Médicos/ética , Recusa em Tratar/legislação & jurisprudência , Aborto Induzido/ética , Aborto Induzido/legislação & jurisprudência , Feminino , Humanos , North Carolina , Médicos/legislação & jurisprudência , Médicos/psicologia , Médicos/normas , Gravidez , Recusa em Tratar/ética , Terminologia como Assunto , Estados Unidos
11.
Biochim Biophys Acta ; 1833(12): 2673-2681, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23827255

RESUMO

RNAi is a highly conserved mechanism in almost every eukaryote with a few exceptions including the model organism Saccharomyces cerevisiae. A recent study showed that the introduction of the two core components of canonical RNAi systems, Argonaute and Dicer, from another budding yeast, Saccharomyces castellii, restores RNAi in S. cerevisiae. We report here that a functional RNAi system can be reconstituted in yeast with the introduction of only S. castellii Dicer and human Argonaute2. Interestingly, whether or not TRBP2 was present, human Dicer was unable to restore RNAi with either S. castellii or human Argonaute. Contrary to previous reports, we find that human Dicer, TRBP2 and Argonaute2 are not sufficient to reconstitute RNAi in yeast when bona fide RNAi precursors are co-expressed. We and others have previously reported that Hsp90 regulates conformational changes in human and Drosophila Argonautes required to accommodate the loading of dsRNA duplexes. Here we show that the activities of both human and S. castellii Argonaute are subject to Hsp90 regulation in S. cerevisiae. In summary, our results suggest that regulation of the RNAi machinery by Hsp90 may have evolved at the same time as ancestral RNAi.


Assuntos
Evolução Molecular , Proteínas de Choque Térmico HSP90/metabolismo , Interferência de RNA , Saccharomyces cerevisiae/metabolismo , Proteínas Argonautas/química , Proteínas Argonautas/metabolismo , Fluorescência , Inativação Gênica , Proteínas de Fluorescência Verde/metabolismo , Humanos , Macrolídeos/farmacologia , Estrutura Terciária de Proteína , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/efeitos dos fármacos , Proteínas de Saccharomyces cerevisiae/metabolismo
12.
J Pediatr Surg ; 59(8): 1538-1544, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38649311

RESUMO

BACKGROUND: Isolated fallopian tube torsion (IFTT) is a rare form of adnexal torsion that is more difficult to diagnose, which may lead to delays in treatment. Our objectives were to identify clinical and radiologic factors associated with surgically-confirmed IFTT and compare them with those of patients without torsion and with adnexal torsion (AT) in a large pediatric population. METHODS: We conducted a retrospective chart review of all patients who underwent surgery for suspected adnexal torsion from 2016 to 2019. Torsion was determined intraoperatively, with IFFT defined as those with only tubal but no ovarian torsion and AT defined as those with ovarian torsion, with or without involvement of the ipsilateral fallopian tube. Clinical and radiologic variables were compared between patients with IFTT and those without torsion and with AT using descriptive statistics. A previously-described composite score to predict torsion based on the presence of vomiting and adnexal volume (VVCS) was calculated for each patient. RESULTS: Of 291 patients who underwent surgery for suspected torsion, 168 had confirmed torsion: 33 (19.6%) IFTT and 135 (80.4%) AT. Patients with IFTT were more likely to be younger (12.8 vs. 14.2 years, P = 0.02), premenarchal (29.0% vs. 10.7%, P = 0.009), experience nausea (90.6% vs. 70.9%, P = 0.02) and vomiting (81.3% vs. 32.8%, P < 0.001), have a paratubal cyst on imaging (18.8% vs. 2.5%, P = 0.003), and have larger adnexal volume (143.3 vs. 64.9 ml, P < 0.001) than those without torsion. Higher BMI (26.6 vs. 22.9 kg/m2, P = 0.03), a paratubal cyst on imaging (18.8% vs. 1.5%, P < 0.001), presence of arterial (65.5% vs. 44.1%, P = 0.04) and venous Doppler flow (79.3% vs. 55.9%, P = 0.02), and radiologic impression indicating lack of torsion (37.9% vs. 16.8%, P = 0.04) were more common in IFTT than AT. The accuracy of the VVCS in predicting torsion for the IFFT group was 83.9%. CONCLUSIONS: IFTT has a similar clinical presentation to AT but with a higher likelihood of a paratubal cyst and preserved Doppler flow on imaging. IFTT should be strongly considered in patients who present with pain, nausea, and vomiting and have an adnexal mass separate from the ovary on imaging, regardless of Doppler flow. LEVEL OF EVIDENCE: Level II. TYPE OF STUDY: Prognosis study.


Assuntos
Doenças das Tubas Uterinas , Anormalidade Torcional , Humanos , Feminino , Estudos Retrospectivos , Criança , Anormalidade Torcional/cirurgia , Anormalidade Torcional/diagnóstico , Adolescente , Doenças das Tubas Uterinas/cirurgia , Doenças das Tubas Uterinas/complicações , Torção Ovariana/cirurgia , Fatores de Risco
13.
Front Mol Biosci ; 11: 1334876, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645275

RESUMO

Heat shock protein 90 (Hsp90) is a molecular chaperone important for maintaining protein homeostasis (proteostasis) in the cell. Hsp90 inhibitors are being explored as cancer therapeutics because of their ability to disrupt proteostasis. Inhibiting Hsp90 increases surface density of the immunological receptor Major Histocompatibility Complex 1 (MHC1). Here we show that this increase occurs across multiple cancer cell lines and with both cytosol-specific and pan-Hsp90 inhibitors. We demonstrate that Hsp90 inhibition also alters surface expression of both IFNGR and PD-L1, two additional immunological receptors that play a significant role in anti-tumour or anti-immune activity in the tumour microenvironment. Hsp90 also negatively regulates IFN-γ activity in cancer cells, suggesting it has a unique role in mediating the immune system's response to cancer. Our data suggests a strong link between Hsp90 activity and the pathways that govern anti-tumour immunity. This highlights the potential for the use of an Hsp90 inhibitor in combination with another currently available cancer treatment, immune checkpoint blockade therapy, which works to prevent immune evasion of cancer cells. Combination checkpoint inhibitor therapy and the use of an Hsp90 inhibitor may potentiate the therapeutic benefits of both treatments and improve prognosis for cancer patients.

14.
Contraception ; 133: 110413, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38401772

RESUMO

OBJECTIVE: Clinical factors related to development of amenorrhea in adolescents with the etonogestrel contraceptive implant are not well-understood. The purpose of this study is to describe what baseline clinical characteristics are associated with amenorrhea in adolescents with a contraceptive implant 12 months after placement. STUDY DESIGN: This retrospective cohort study included 252 post-menarchal individuals aged 12-22 years with a contraceptive implant placed between 2016-2020. Data abstracted at insertion, three months post-insertion, and 12 months post-insertion included demographics, baseline bleeding pattern, prior contraception use, post-insertion bleeding pattern, and method discontinuation. We assessed possible predictive characteristics of our outcomes using bivariate and multivariable logistic regression analyses. RESULTS: Twenty nine percent of patients were amenorrheic 12 months after placement. Patients who were amenorrheic at 12 months were more likely to be obese (41.1% vs 24.6%, p = 0.01), to have been amenorrheic prior to implant insertion (16.9% vs 5.4%, p < 0.01, to have used hormonal contraception immediately prior to insertion (42.5% vs 26.3%, p = 0.01), to have had the most recent contraceptive method being another implant (12.3% vs 3.6%, p = 0.02), and to have developed amenorrhea within three months after placement (22.2% vs 12.6%, p < 0.01). After multivariable regression analysis, only obesity (adjusted odds ratio [aOR] 2.2 95% CI 1.1-4.2) and amenorrhea at three months (aOR 3.6, CI 1.1-11.5) were associated with amenorrhea at 12 months. CONCLUSION: Obesity and early amenorrhea were associated with 12-month amenorrhea in adolescents using the etonogestrel subdermal implant. Understanding this can help with contraceptive method selection and counseling for patients and providers. IMPLICATIONS: Obesity and early amenorrhea with the etonogestrel contraceptive implant are associated with longer-term amenorrhea in adolescents using this method. These findings can aid providers with method selection and pre-insertion decision-making for adolescents considering contraceptive implant use, as well as continued counseling after placement.


Assuntos
Anticoncepcionais Femininos , Feminino , Humanos , Adolescente , Anticoncepcionais Femininos/efeitos adversos , Amenorreia/induzido quimicamente , Estudos Retrospectivos , Desogestrel/efeitos adversos , Obesidade , Implantes de Medicamento/efeitos adversos
15.
J Pediatr Adolesc Gynecol ; 37(1): 45-50, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37871845

RESUMO

STUDY OBJECTIVE: To describe the demographic characteristics and psychological symptoms of gender-diverse patients and to compare symptoms between prepubertal and pubertal subgroups METHODS: This was a retrospective chart review of all gender-diverse patients seen by at least 1 provider at the Nemours Gender Wellness Program from March 2015 to December 2020. The extracted data included demographic and psychosocial characteristics at baseline and 1-year follow-up visits. Pubertal status was determined by Tanner staging by a pediatric endocrinologist or gynecologist. Descriptive statistics were used to compare these variables between prepubertal and pubertal subgroups. RESULTS: Our sample included 177 individuals at baseline and 96 subjects at the 1-year follow-up visit. Most patients were White (83.0%), non-Hispanic (92.0%), transgender male (72.9%), and pubertal (90.4%). Compared with prepubertal patients, at the baseline visit, pubertal patients had significantly higher rates of current (68.1% vs 17.6%, P < .001) and lifetime (80.0% vs 23.5%, P < .001) depressive symptoms, current anxiety symptoms (70.0% vs 41.2%, P = .01), lifetime suicide attempts (12.5% vs 0%, P < .001), and a formal diagnosis of an eating disorder (5.0% vs 0%, P < .001). Symptoms did not change significantly over time from baseline to the 1-year follow-up visit. CONCLUSION: We found elevated rates of psychological symptoms and diagnoses in gender-diverse youth, with higher rates in pubertal compared with prepubertal patients. By elucidating how the psychosocial characteristics of gender-diverse children and adolescents differ based on pubertal status, these data can be used to improve current outreach and treatment strategies for transgender pediatric patients.


Assuntos
Transtornos da Alimentação e da Ingestão de Alimentos , Pessoas Transgênero , Adolescente , Humanos , Masculino , Criança , Pessoas Transgênero/psicologia , Estudos Retrospectivos , Identidade de Gênero , Ansiedade/epidemiologia
16.
F S Rep ; 4(1): 36-42, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36959965

RESUMO

Objective: To identify factors influencing sperm donor willingness to participate in direct-to-consumer genetic testing, comfort with sharing genetically identifiable data in commercial genetic testing databases, and likelihood to donate sperm again. Design: Cross-sectional online anonymous survey. Setting: Multicenter, 2 large American sperm banks from July 1, 2020 to July10, 2021. Patients: Sperm donors from 1980 to 2020. Interventions: None. Main outcome measures: Associations between donor demographic characteristics, donation history, and attitudes toward direct-to-consumer genetic testing. Results: A total of 396 donors completed the survey. Most donations (61.5%) occurred from 2010 to 2020, and 34.3% were nonidentified donations. Nonidentified donors were less comfortable with their genetic data being shared than open-identity donors (25.4% vs. 43.8%) and were less likely than open-identity donors to donate sperm again (43.3% vs. 72.1%). Donors who donated after the inception of direct-to-consumer genetic testing in 2007 were less likely to participate in commercial genetic testing than those who donated before 2007 (25.8% vs. 37.1%). Most donors (87.4%) have disclosed their donation(s) to current partners, but fewer have disclosed them to their families (56.6%) or children (30.5%). Of the donors who had been contacted by donor-conceived persons, 79.5% were identified via direct-to-consumer genetic testing. Overall, 61.1% of donors would donate again regardless of direct-to-consumer genetic testing. Conclusions: Direct-to-consumer genetic testing is playing a dynamic role in sperm donor identification, but donors seem willing to donate again. Implication counseling regarding future linkage and contact from donor-conceived persons needs to be standardized for potential donors before donation.

17.
J Pediatr Surg ; 58(4): 767-773, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36008196

RESUMO

BACKGROUND: Adnexal torsion is a gynecologic emergency in children and adolescents but remains a challenging diagnosis, with no consistent clinical or radiologic diagnostic criteria. Our objective was to identify risk factors associated with adnexal torsion in premenarchal and menarchal patients with surgically confirmed torsion compared with those without torsion. METHODS: We conducted a retrospective chart review of all patients who underwent surgery between January 2016 and December 2019 for possible adnexal torsion. Data on demographics, clinical characteristics, radiologic variables, and operative findings were compared using descriptive statistics. Independent predictors of torsion were then examined in multivariate logistic regression models. RESULTS: Of the 291 patients who underwent surgery, 168 (57.7%) had torsion. Patients with torsion were younger than those without torsion (11.9 vs. 14.2 years, P < .01). Vomiting was significantly associated with torsion for all patients (P < .001). Large adnexal volume and absent arterial Doppler flow were associated with torsion for the total population and menarchal subgroup. A logistic regression model for the total population that controlled for age and menarchal status found that vomiting (adjusted odds ratio [aOR] 5.92, 95% confidence interval [CI] 2.87-12.22), highest adnexal volume category (aOR 4.92, 95% CI 2.25-10.75), and absent arterial Doppler flow (aOR 2.674, 95% CI 1.28-5.60) were associated with torsion. CONCLUSIONS: Vomiting, enlarged adnexal volume, and absent arterial Doppler flow were associated with adnexal torsion. However, no single risk factor accurately diagnosed torsion, and multiple factors should be interpreted together. LEVEL OF EVIDENCE: Study of Diagnostic Test, Level II.


Assuntos
Doenças dos Anexos , Criança , Feminino , Humanos , Adolescente , Doenças dos Anexos/diagnóstico por imagem , Doenças dos Anexos/cirurgia , Doenças dos Anexos/complicações , Torção Ovariana , Estudos Retrospectivos , Anormalidade Torcional/diagnóstico por imagem , Anormalidade Torcional/cirurgia , Anormalidade Torcional/complicações , Vômito/etiologia
18.
Am J Obstet Gynecol MFM ; 4(4): 100643, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35405372

RESUMO

BACKGROUND: Pelvic inflammatory disease during pregnancy is a rare and an understudied occurrence with potential negative outcomes. OBJECTIVE: This study aimed to evaluate the outcomes of pregnant women with pelvic inflammatory disease with or without pelvic abscesses. DATA SOURCES: We performed a systematic review of the literature using Ovid MEDLINE, Scopus, CINAHL, and PubMed (including Cochrane) with no time limitations. STUDY ELIGIBILITY CRITERIA: Relevant studies on pelvic inflammatory disease during pregnancy were identified and considered eligible if they described at least 1 case of pelvic inflammatory disease after conception, defined as infection in one or more of the following: uterus, fallopian tubes, and ovaries; based on clinical findings, physical examination, and imaging with or without pelvic abscesses present. Only studies on pelvic inflammatory disease with or without tubo-ovarian abscesses during pregnancy that evaluated perinatal outcomes were included. Data on the risk factors, delivery methods, and maternal, fetal, and neonatal outcomes were collected. METHODS: Reviewers screened all relevant titles using the inclusion/exclusion criteria and selected relevant articles for appraisal. A total of 49 cases with reported pelvic inflammatory disease, pelvic abscesses, or both were included. RESULTS: After exclusion of articles that did not meet the inclusion criteria, 34 manuscripts describing the occurrence of pelvic inflammatory disease in 49 pregnancies were analyzed, focusing primarily on cases reported after 1971. The mean age of patients was 25±6.3 years, the mean gestational age at diagnosis was 19.0±10.3 weeks, and 67.6% of patients were multiparous. Of all included patients, 27 (62.8%) underwent exploratory laparotomies, 14 (32.6%) underwent unilateral salpingo-oophorectomies, and 11 (25.6%) underwent appendectomies. Of all the deliveries, 13 (50%) pregnancies were full term, 14 (53.8%) were cesarean deliveries, 10 (38.5%) were spontaneous vaginal deliveries, and 2 (7.7%) were cesarean hysterectomies. There were 26 (60.5%) cases of viable births (mean gestational age at delivery, 33.8±5.1 weeks) and 17 (39.5%) cases of nonviable births. Sepsis was a complication in 3 (7.0%) cases and caused 3 neonatal deaths. CONCLUSION: Although rare, pelvic inflammatory disease can have severe health consequences. Risk factors for pelvic inflammatory disease development include maternal pelvic structural anomalies, a history of sexually transmitted infections, recent pelvic surgery, and in vitro fertilization or oocyte retrieval. Pelvic inflammatory disease can coincide with pregnancy and can occur in the second trimester. Making a prompt diagnosis can help to improve the outcomes; therefore, if a high enough suspicion exists, treatment should not be delayed.


Assuntos
Doença Inflamatória Pélvica , Abscesso , Cesárea , Feminino , Idade Gestacional , Humanos , Parto , Doença Inflamatória Pélvica/diagnóstico , Doença Inflamatória Pélvica/epidemiologia , Doença Inflamatória Pélvica/terapia , Gravidez
19.
Obstet Gynecol ; 139(2): 244-253, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34991140

RESUMO

OBJECTIVE: To describe postpartum experiences of women who gave birth during the coronavirus disease 2019 (COVID-19) pandemic, to identify short-term and long-term opportunities to address maternal-child health during this pandemic. METHODS: This qualitative photo-elicitation study asked 30 women between 3 and 10 weeks postpartum to take photographs that encompassed their experience as a new mother during the pandemic. Two trained interviewers elicited elements of this experience using the photos as an anchor during virtual, hour-long interviews. Interview transcripts were analyzed using directed content analysis, including open coding to identify key ideas, codebook development, and codebook refinement. Half of transcripts were team coded to ensure coding accuracy. After coding, the study team organized codes to inform the development of an explanatory model. RESULTS: Interviews identified important stressors new mothers experienced that were worsened during the pandemic, namely fear, child care, older children, loss, isolation, and employment. Interviews also highlighted key support structures (self-care, interpersonal, and structural supports) that were at times helpful in alleviating stressors and at others were inadequate to counter stress and even enhanced stress. CONCLUSION: For postpartum individuals overall, the pandemic resulted in increased strain during an already stressful time. These findings demonstrate inadequacy of support systems for postpartum women and may highlight action items for stakeholders to improve postpartum care during the pandemic and in the future.


Assuntos
COVID-19/psicologia , Mães/psicologia , Período Pós-Parto/psicologia , Adulto , Feminino , Humanos , Pennsylvania/epidemiologia , Fotografação , Pesquisa Qualitativa , SARS-CoV-2
20.
Am J Obstet Gynecol MFM ; 2(2): 100086, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-33345957

RESUMO

BACKGROUND: After careful review of the ARRIVE trial (A Randomized Trial of Induction Versus Expectant Management) data, induction of labor prior to one's due date in the absence of maternal and fetal indications (which the American College of Obstetricians and Gynecologists currently refers to as "elective") is now endorsed as a "reasonable" option by the American College of Obstetricians and Gynecologists (ACOG). As a result, there has been much discussion among providers regarding how best to operationalize this ACOG recommendation into shared decision making regarding delivery planning. However, we lack a formal understanding of the perspectives of patients themselves on this topic. OBJECTIVE: To assess patient understanding and preference for induction of labor prior to one's due date. MATERIALS AND METHODS: We conducted an anonymous, cross-sectional survey of women in their third trimester of pregnancy presenting for routine obstetric care in August 2018. The survey included a series of questions designed to assess basic demographics, obstetric history, and patient understanding and opinions about the practice of induction of labor, with a focus on induction of labor prior to one's due date in the absence of maternal and fetal indications. RESULTS: A total of 108 women were approached for participation, and 100 women participated in this survey (93% participation). Of the participants, 99% were supportive of induction of labor for fetal indications, and 96% were supportive for maternal indications prior to one's due date. In contrast, 54% of participants were not interested in induction of labor in the absence of maternal and fetal indications prior to one's due date. Women opposed to induction of labor in the absence of maternal and fetal indications were almost 4 times more likely to be concerned about the possibility that induction of labor in the absence of maternal and fetal indications could cause fetal harm (odds ratio, 3.9; confidence interval, 1.2-13.2). CONCLUSION: Nearly all women surveyed in our pilot study were interested in induction of labor prior to one's due date for maternal or fetal indications. 46% of those surveyed were interested in induction of labor in the absence of maternal and fetal indications prior to their due date. Concern about potential fetal harm was more likely among women opposed to induction of labor in the absence of maternal and fetal indications. As providers discuss delivery planning with their patients, these results may provide a useful context for operationalizing and individualizing the results of the ARRIVE trial for their patients.


Assuntos
Trabalho de Parto , Estudos Transversais , Feminino , Feto , Humanos , Trabalho de Parto Induzido , Projetos Piloto , Gravidez
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