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1.
J Eat Disord ; 12(1): 29, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374089

RESUMO

INTRODUCTION: Eating disorders are a worldwide public health concern with the United States having a particularly high prevalence. Eating disorders are of particular concern to the Department of Defense and Military Health System (MHS) because body composition standards are in place for active-duty service members. METHODS: We conducted a cross-sectional study of active-duty service women (ADSW) ages 18 and older in the U.S. Army, Air Force, Navy, and Marine Corps during fiscal years (FY) 2018-2019. Utilizing claims data from the MHS Data Repository (MDR), we identified ADSW with a Body Mass Index (BMI) measure during the study period and compared their BMI to Service-specific requirements and diagnosis of an eating disorder. RESULTS: We identified a total of 161,209 ADSW from the MDR in FYs 2018-2019 with a recorded BMI, of whom 61,711 (38.3%) had a BMI exceeding the maximum BMI Service-specific standards during the study period and 0.5% had an eating disorder diagnosis. Increased risk of an eating disorder was found in ADSW with an Underweight BMI. Further, we found that there was no association of disordered eating diagnoses among ADSW who were near the maximum height/weight standard set by their Service. CONCLUSION: There appears to be no association between body composition standards of the Services and eating disorder diagnoses in ADSW. We were not able to investigate unhealthy habits around diet or exercise directly related to body composition standards.


Eating disorders are a worldwide public health concern with the United States having a particularly high prevalence. Active duty service women serving in the United States armed forces may be at an increased risk due to strict Service specific weight requirements. This study suggests that the height and weight standards do not increase the risk for eating disorder diagnoses in active duty service women. However, we were not able to investigate unhealthy habits around diet or exercise directly related to body composition standards near the time of measurement or assessment.

3.
J Surg Educ ; 80(12): 1850-1858, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37739890

RESUMO

OBJECTIVE/BACKGROUND: Kidney transplantation is a complex operation that incorporates multiple fundamental surgical techniques and is an excellent opportunity for surgical skill development during residency training. We hypothesized that increasing resident competency, measured as anastomosis time, could be demonstrated while maintaining high-quality surgical outcomes during the learning process. METHODS: We performed a retrospective cohort study of surgical resident involvement in kidney transplantation and recorded the anastomosis time. The study population comprised adult, single organ kidney transplants (n = 2052) at a large academic transplant center between 2006 and 2019. Descriptive statistics included frequencies, medians, and means. A mixed model of anastomosis time on number of procedures was fitted. Poisson models were fitted with outcomes of the number of patients with delayed graft function and number of patients that underwent reoperation postoperatively, with the exposure being number of kidney transplants performed by resident. RESULTS: Results from the mixed model suggest that as the number of times a resident performs the surgery increases, the time to conduct the operation decreases with statistical significance. The Poisson regression demonstrated no significant relationship between the operative volume of a resident and postoperative complications. CONCLUSION: This study demonstrated statistical evidence that with an increase in the number of renal transplantations performed by a surgical resident, anastomosis time decreased. It also demonstrated no significant relationship between number of kidney transplants performed by a resident and postoperative complications, suggesting that patient outcomes for this operation are not adversely affected by resident involvement.


Assuntos
Internato e Residência , Transplante de Rim , Adulto , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia
4.
J Bone Joint Surg Am ; 105(21): 1734-1739, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37315108

RESUMO

BACKGROUND: Leadership of clinical trials confers national recognition and promotes academic advancement. We hypothesized that women would be underrepresented among principal investigators (PIs) of hip and knee arthroplasty clinical trials in the United States. METHODS: A query of hip and knee arthroplasty clinical trials from 2015 to 2021 was performed on ClinicalTrials.gov. Clinical trials were included if they involved a U.S.-based orthopaedic-surgeon PI. We analyzed the sex representation of arthroplasty PIs among junior-level (assistant professor) and senior-level (associate or full professor) faculty. Participation-to-prevalence ratios (PPRs) were calculated by comparing the sex representation among arthroplasty PIs with that among academic arthroplasty faculty at institutions conducting hip and knee arthroplasty clinical trials. A PPR of <0.8 indicated underrepresentation and a PPR of >1.2 indicated overrepresentation. RESULTS: A total of 157 clinical trials involving 192 arthroplasty PIs were included. Of these PIs, only 2 (1.0%) were women. PIs were mostly funded by academic institutions (66%) and industry (33%). U.S. federal sources funded a minority (1%) of PIs. Of the 243 male arthroplasty faculty who were eligible, 190 men (78.2%) served as PIs. In contrast, of the 17 female arthroplasty faculty who were eligible, only 2 women (11.8%) served as PIs (p < 0.001). Across the entire cohort of arthroplasty PIs, women were underrepresented (PPR = 0.16), whereas men were equitably represented (PPR = 1.06). Women were underrepresented at the assistant professor (PPR = 0.0), associate professor (PPR = 0.52), and full professor (PPR = 0.58) levels. CONCLUSIONS: Women were underrepresented among PIs of hip and knee arthroplasty clinical trials, which may lead to disparities in academic promotion and advancement. More research is needed to understand the potential barriers to female leadership of clinical trials. Greater awareness and engagement are needed to create sex equity in clinical trial leadership for hip and knee arthroplasty research. CLINICAL RELEVANCE: The underrepresentation of women among arthroplasty PIs may lead to fewer options in surgical providers for patients and may limit access to musculoskeletal care for certain patient populations. A diverse arthroplasty workforce can promote attention to issues that disproportionately affect historically underrepresented and vulnerable patient populations.


Assuntos
Sucesso Acadêmico , Artroplastia do Joelho , Cirurgiões Ortopédicos , Humanos , Masculino , Feminino , Estados Unidos , Grupos Minoritários , Docentes , Docentes de Medicina
5.
Transgend Health ; 8(3): 231-237, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37342474

RESUMO

Purpose: Transgender individuals have been systemically excluded from U.S. health care, creating barriers and disparities that other populations do not face. Gender-affirming surgery represents an emerging treatment modality for gender dysphoria, however, little is known about how transgender patients experience the perioperative pathway. This study sought to characterize the experiences of transgender patients seeking gender-affirming surgery and identify opportunities for improvement. Methods: A qualitative study was conducted at an academic medical center between July and December 2020. Semistructured interviews were conducted after a postoperative encounter with adult patients who had undergone gender-affirming surgery within the past year. A purposive sampling strategy was used to maximize representation across surgery types and surgeons. Recruitment continued until thematic saturation was reached. Results: All invited patients agreed to participate, yielding 36 interviews (response rate=100%). Four major themes emerged. First, gender-affirming surgery was described as a major life event, often reflecting years of personal decision making and research. Second, participants stressed the importance of surgeon investment, surgeon experience caring for transgender patients, and individualized care in developing a strong relationship with their care team. Third, self-advocacy was necessary to navigate the perioperative pathway and overcome barriers. Last, participants discussed a lack of equity and provider awareness regarding transgender health issues, including correct pronoun usage, terminology, and insurance coverage. Conclusion: Patients undergoing gender-affirming surgery encounter unique perioperative barriers to care, which would benefit from targeted interventions in the health care system. To improve the pathway, our findings support the creation of multidisciplinary gender-affirmation clinics, greater emphasis on transgender care in medical education, and insurance policy reforms aimed at promoting consistent and equitable coverage.

6.
Front Physiol ; 14: 1108304, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36926194

RESUMO

Exposure to hypoxia, due to high altitude or chronic lung disease, leads to structural changes in the pulmonary vascular wall, including hyperplasia and migration of pulmonary arterial smooth muscle cells (PASMCs). Previous studies showed that hypoxia upregulates the expression of Na+/H+ exchanger isoform 1 (NHE1) and that inhibition or loss of NHE1 prevents hypoxia-induced PASMC migration and proliferation. The exact mechanism by which NHE1 controls PASMC function has not been fully delineated. In fibroblasts, NHE1 has been shown to act as a membrane anchor for actin filaments, via binding of the adaptor protein, ezrin. Thus, in this study, we tested the role of ezrin and NHE1/actin interactions in controlling PASMC function. Using rat PASMCs exposed to in vitro hypoxia (4% O2, 24 h) we found that hypoxic exposure increased phosphorylation (activation) of ezrin, and promoted interactions between NHE1, phosphorylated ezrin and smooth muscle specific α-actin (SMA) as measured via immunoprecipitation and co-localization. Overexpression of wild-type human NHE1 in the absence of hypoxia was sufficient to induce PASMC migration and proliferation, whereas inhibiting ezrin phosphorylation with NSC668394 suppressed NHE1/SMA co-localization and migration in hypoxic PASMCs. Finally, overexpressing a version of human NHE1 in which amino acids were mutated to prevent NHE1/ezrin/SMA interactions was unable to increase PASMC migration and proliferation despite exhibiting normal Na+/H+ exchange activity. From these results, we conclude that hypoxic exposure increases ezrin phosphorylation in PASMCs, leading to enhanced ezrin/NHE1/SMA interaction. We further speculate that these interactions promote anchoring of the actin cytoskeleton to the membrane to facilitate the changes in cell movement and shape required for migration and proliferation.

8.
Orthop J Sports Med ; 10(7): 23259671221105257, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35898206

RESUMO

Background: The extent to which concussions affect Women's National Basketball Association (WNBA) athletes has not been thoroughly examined. Purpose: To evaluate the incidence and impact of concussion injuries occurring in the WNBA. Study Design: Descriptive epidemiology study. Methods: Publicly available records were searched to identify all documented basketball-related concussions from WNBA seasons 1997 to 2020. Player demographics, injury details, and basketball career information were collected. Concussion incidence and return-to-play (RTP) timing were evaluated before and after the institution of the WNBA concussion protocol in 2012. Minutes per game and game score per minute were compared 5 games before and 5 games after the concussion was sustained. Player game availability and RTP performance were also compared with an age-, body mass index-, position-, and experience-matched control group of players who did not sustain any injuries during the index season. Results: A total of 70 concussions among 55 players were reported in the WNBA from 1997 to 2020, with a mean incidence of 2.9 ± 2.3 concussions per season. After the implementation of the WNBA concussion protocol, the incidence significantly increased from 1.7 to 5.0 concussions per season (P < .001). All players returned after a first-time concussion, missing a mean of 3.8 ± 4.7 games and 17.9 ± 20.7 days. After the adoption of the concussion protocol, the time to RTP significantly increased with games missed (P = .006) and days missed (P = .006). Minutes per game and game score per minute were not significantly affected by sustaining a concussion (P = .451 and P = .826, respectively). Conclusion: Since the adoption of the WNBA concussion protocol in the 2012 season, the incidence of concussions increased significantly. Athletes retained a high rate of RTP after missing a median of 4 games, and the time to RTP increased after the institution of the concussion protocol. Player game availability and performance within the same season were not significantly affected by concussion injuries after a successful RTP.

9.
Am Surg ; 88(9): 2230-2232, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35503030

RESUMO

Radiation-associated sarcomas (RASs) are rare entities that tend to have an aggressive course and poor prognosis. Criteria for diagnosis of radiation-associated sarcoma include therapeutic radiation preceding the development of sarcoma, sarcoma arising within or near the irradiated field, and tumor histology that is distinct from the primary tumor necessitating radiation. Despite their relatively uncommon occurrence, RASs are a well-established complication of radiation therapy. We present the complex, multidisciplinary surgical management of a patient with multi-compartmental radiation-associated sarcoma of the left retroperitoneum occurring nearly 25 years after undergoing whole trunk radiation for Hodgkin's lymphoma.


Assuntos
Doença de Hodgkin , Neoplasias Retroperitoneais , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Neoplasias Retroperitoneais/complicações , Neoplasias Retroperitoneais/radioterapia , Neoplasias Retroperitoneais/cirurgia , Sarcoma/radioterapia , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/patologia
10.
Am Surg ; 88(8): 1931-1932, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35392681

RESUMO

Recognition of gender diverse individuals and their unique health care needs is increasing. Population-based studies demonstrate numbers of individuals identifying as transgender and gender non-binary is growing, particularly in younger generations. Since the end of Medicare coverage exclusion for gender-affirming surgeries (GASs) and expansion in third-party coverage, patients seeking GAS have increased dramatically.Gender-affirming chest surgery (GACS) is performed at nearly twice the rate of genital surgery. The average age of patients seeking GAS is 29.8 years. With expansion in GAS availability, more individuals at or near screening age present for chest surgery. Without pre-operative imaging, breast tissue abnormalities may not be discovered until surgical pathology. We present a patient with Paget's disease of the breast (PDB) discovered after female-to-male gender-affirming chest surgery (FTM GACS) without pre-operative imaging. This case highlights the importance of routine breast surveillance prior to FTM GACS.


Assuntos
Cirurgia de Readequação Sexual , Pessoas Transgênero , Adulto , Idoso , Feminino , Humanos , Masculino , Programas de Rastreamento , Medicare , Tórax , Estados Unidos
11.
Health Soc Care Community ; 30(5): e1701-e1710, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34617649

RESUMO

Millions of people in the United States provide unpaid care to family and friends with long-term illnesses and disabilities. Research shows that informal caregiving can be beneficial for recipients of care, but taxing for those providing care. Studies have not explored associations between informal caregiving and the risk of experiencing different forms of material hardship. In this study, we use data from the Survey of Income and Program Participation (N = 31,633) to address this gap in the literature. The sample was drawn from a multistage-stratified sample of the civilian, non-institutionalised population of the United States. We analyse data that were collected in 2011 and find that providing informal care to others is associated with an increased risk of experiencing healthcare hardship, bill-paying hardship and food insecurity. Moreover, we find that household financial resources mediate the association between caregiving and material hardship. As a result, while caregiving households face a higher risk of experiencing material hardships at all income levels, the disparity is largest at low incomes and smallest at high incomes. The findings highlight the need for a stronger safety net for informal caregivers.


Assuntos
Cuidadores , Pobreza , Emprego , Características da Família , Humanos , Renda , Estados Unidos
12.
Acad Emerg Med ; 28(12): 1389-1398, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34490665

RESUMO

OBJECTIVE: Emergency medicine clinicians are excellent at identifying and treating physical trauma as a chief complaint, but are often unaware of patients' previous experiences of trauma. The purpose of this study was to describe emergency department (ED) patients' lifetime experiences of trauma. METHODS: The investigative team used framework analysis to examine 1,282 participants' open-ended responses to the Vera Institute's Trafficking Victim Identification Tool questions. Of these, 204 participants were found to have experienced at least one form of trauma; none of these participants were assessed positive for a human trafficking experience. RESULTS: From 204 participants, 343 instances of trauma were recorded and analyzed. Of the 204 patient-participants who reported trauma, 96 experienced one form of trauma and 108 experienced two or more. Three major themes emerged: work trauma (experiences of trauma originating in the workplace), coercion (being manipulated into activities), and trauma connections (some forms of trauma were commonly experienced with other kinds of trauma). A fourth, less prominent, theme was disclosure as witness (participants witnessing trauma). CONCLUSION: ED patients have experienced many forms of lifetime trauma and, in this study, were willing to share about their experiences while in the acute care setting. Given the common experience of trauma among the ED patients in this investigation, more work is needed to examine if and how trauma-informed care principles should be employed in the ED. Additionally, the ED may be an underutilized data source for researchers seeking participants with experiences of trauma and/or a point of connection for trauma survivors to be linked to trauma care services.


Assuntos
Serviço Hospitalar de Emergência , Sobreviventes , Humanos , Local de Trabalho
13.
Transplant Direct ; 7(10): e761, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34514116

RESUMO

Transplantation of hepatitis C viremic (HCV+) deceased donor kidney transplants (DDKT) into aviremic (HCV-) recipients is a strategy to increase organ utilization. However, there are concerns around inferior recipient outcomes due to delayed initiation of direct-acting antiviral (DAA) therapy and sustained HCV replication when implemented outside of a research setting. METHODS: This was a retrospective single-center matched cohort study of DDKT recipients of HCV+ donors (cases) who were matched 1:1 to recipients of HCV- donors (comparators) by age, gender, race, presence of diabetes, kidney donor profile index, and calculated panel-reactive antibody. Data were analyzed using summary statistics, t-tests, and chi-square tests for between-group comparisons, and linear mixed-effects models for longitudinal data. RESULTS: Each group consisted of 50 recipients with no significant differences in baseline characteristics. The 6-mo longitudinal trajectory of serum creatinine and estimated glomerular filtration rate did not differ between groups. All recipients had similar rates of acute rejection and readmissions (all P > 0.05). One case lost the allograft 151 d posttransplant because of acute rejection, and 1 comparator died on postoperative day 7 from cardiac arrest. HCV+ recipients initiated DAA on average 29 ± 11 d posttransplant. Ninety-eight percent achieved sustained virologic response at 4 and 12 wks with the first course of therapy; 1 patient had persistent HCV infection and was cured with a second course of DAA. CONCLUSIONS: Aviremic recipients of HCV+ DDKT with delayed DAA initiation posttransplant had similar short-term outcomes compared with matched recipient comparators of HCV- donors.

14.
Breastfeed Med ; 16(11): 863-868, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34143654

RESUMO

Objective: Intergenerational transmission of breastfeeding attitudes and behaviors from mother to daughter are well known, but there is limited research on intragenerational transmission of breastfeeding attitudes or behaviors within families. This study aimed to understand how initiation and duration of breastfeeding are influenced by past breastfeeding experiences of sisters among women in a longitudinal population-based cohort. Methods: Data were obtained on women enrolled in the 1979 National Longitudinal Survey of Youth (NLSY) who had at least one child enrolled in a substudy of cohort members' children. For each mother in the study, we determined whether any of her sisters also enrolled in the main NLSY study had previously breastfed one of their children. Results: Mothers whose sister(s) had prior breastfeeding experience were more likely to breastfeed their first-born child on unadjusted analysis (70% versus 45%, chi-square p < 0.001) and had a longer median of breastfeeding duration (median 14.5 versus 12 weeks, rank-sum p = 0.039). However, on a multivariable analysis accounting for potential confounding by maternal characteristics, infant characteristics, and differences among households, sisters' breastfeeding experience was no longer independently associated with the likelihood of breastfeeding initiation (odds ratio: 1.16; confidence interval [95% CI]: 0.73-1.85; p = 0.520) or the hazard of breastfeeding discontinuation (hazard ratio: 0.96; 95% CI: 0.82-1.12; p = 0.598). Conclusion: After adjusting for socioeconomic characteristics, intragenerational transmission of breastfeeding behavior was negligible among mothers raised in the same household. Other forms of intragenerational transmission (e.g., influence of extended family members) may be more salient influences on women's decision to breastfeed.


Assuntos
Aleitamento Materno , Mães , Adolescente , Criança , Estudos de Coortes , Feminino , Humanos , Lactente , Estudos Longitudinais , Inquéritos e Questionários
15.
J Rural Health ; 37(4): 705-713, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33226683

RESUMO

PURPOSE: Preserving and increasing the health care workforce in rural areas has become imperative due to the shortage of health care workers serving rural populations. However, limited data are available on long-term patterns of employment in rural settings among health care workers. METHODS: We analyzed the National Longitudinal Survey of Youth, which enrolled a nationally representative sample of adolescents in 1979 and tracked their career outcomes through 2016. Using the US Census Bureau occupation codes, we identified participants who worked in health care occupations, and we classified their employment in rural versus urban areas. FINDINGS: Of the 1,007 respondents (including 109 doctoral health professionals), 70% worked only in urban locations, 13% worked only in rural locations, and 17% worked in both rural and urban locations during their health care career. Rural upbringing, White race, and female gender were associated with rural employment. Among nondoctoral health professionals, lower educational attainment was associated with increased likelihood of working only in rural settings. CONCLUSION: Our study indicates the rural workforce is split between workers who are only employed in rural settings, and those who are intermittently employed in rural and urban settings. Therefore, retention of health care workers in rural settings and recruitment of workers from urban settings to practice in rural areas are important strategies for addressing the rural health care worker shortage. Rural upbringing, previously described as predictive of physician practice in rural locations, appears the strongest predictor of rural employment for both doctoral health professionals and nondoctoral health professionals.


Assuntos
Serviços de Saúde Rural , População Rural , Adolescente , Emprego , Feminino , Pessoal de Saúde , Humanos , Estudos Longitudinais
16.
Physiol Rep ; 6(9): e13698, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29756391

RESUMO

Excessive production of endothelin-1 (ET-1) has been observed in almost all forms of pulmonary hypertension. ET-1, a highly potent vasoconstrictor, can also potentiate pulmonary arterial smooth muscle cell (PASMC) growth and migration, both of which contribute to the vascular remodeling that occurs during the development of pulmonary hypertension. Increasing evidence indicates that alkalinization of intracellular pH (pHi ), typically due to activation of Na+ /H+ exchange (NHE), is associated with enhanced PASMC proliferation and migration. We recently demonstrated that application of exogenous ET-1 increased NHE activity in murine PASMCs via a mechanism requiring Rho kinase (ROCK). However, whether ROCK and/or increased NHE activity mediate ET-1-induced migration and proliferation in PASMCs remains unknown. In this study, we used fluorescent microscopy in transiently cultured PASMCs from distal pulmonary arteries of the rat and the pH-sensitive dye, BCECF-AM, to measure changes in resting pHi and NHE activity induced by exposure to exogenous ET-1 (10-8  mol/L) for 24 h. Cell migration and proliferation in response to ET-1 were also measured using Transwell assays and BrdU incorporation, respectively. We found that application of exogenous ET-1 had no effect on NHE1 expression, but increased pHi , NHE activity, migration, and proliferation in rat PASMCs. Pharmacologic inhibition of NHE or ROCK prevented the ET-1-induced changes in cell function (proliferation and migration). Our results indicate that ET-1 modulates PASMC migration and proliferation via changes in pHi homeostasis through a pathway involving ROCK.


Assuntos
Movimento Celular , Proliferação de Células , Endotelina-1/metabolismo , Músculo Liso Vascular/metabolismo , Artéria Pulmonar/metabolismo , Trocadores de Sódio-Hidrogênio/metabolismo , Quinases Associadas a rho/metabolismo , Animais , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Endotelina-1/administração & dosagem , Concentração de Íons de Hidrogênio , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Cultura Primária de Células , Artéria Pulmonar/efeitos dos fármacos , Ratos Wistar
17.
Physiol Rep ; 4(6)2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27009277

RESUMO

Abnormal proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) are hallmark characteristics of vascular remodeling in pulmonary hypertension induced by chronic hypoxia. In this study, we investigated the role of the Na(+)/H(+)exchanger (NHE) and alterations in intracellularpH(pHi) homeostasis in meditating increased proliferation and migration inPASMCs isolated from resistance-sized pulmonary arteries from chronically hypoxic rats or from normoxic rats that were exposed to hypoxia ex vivo (1% or 4% O2, 24-96 h). We found thatPASMCs exposed to either in vivo or ex vivo hypoxia exhibited greater proliferative and migratory capacity, elevated pHi, and enhancedNHEactivity. TheNHEinhibitor, ethyl isopropyl amiloride (EIPA), normalized pHiin hypoxicPASMCs and reduced migration by 73% and 45% in cells exposed to in vivo and in vitro hypoxia, respectively. Similarly,EIPAreduced proliferation by 97% and 78% in cells exposed to in vivo and in vitro hypoxia, respectively. We previously demonstrated thatNHEisoform 1 (NHE1) is the predominant isoform expressed inPASMCs. The development of hypoxia-induced pulmonary hypertension and alterations inPASMC pHihomeostasis were prevented in mice deficient forNHE1. We found that short-term (24 h) ex vivo hypoxic exposure did not alter the expression ofNHE1, so we tested the role of Rho kinase (ROCK) as a possible means of increasingNHEactivity. In the presence of theROCKinhibitor, Y-27632, we found that pHiandNHEactivity were normalized and migration and proliferation were reduced inPASMCs exposed to either in vivo (by 68% for migration and 22% for proliferation) or ex vivo (by 43% for migration and 17% for proliferation) hypoxia. From these results, we conclude that during hypoxia, activation ofROCKenhancesNHEactivity and promotesPASMCmigration and proliferation.


Assuntos
Proteínas de Transporte de Cátions/metabolismo , Movimento Celular , Proliferação de Células , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Músculo Liso Vascular/enzimologia , Miócitos de Músculo Liso/enzimologia , Trocadores de Sódio-Hidrogênio/metabolismo , Remodelação Vascular , Quinases Associadas a rho/metabolismo , Amidas/farmacologia , Amilorida/análogos & derivados , Amilorida/farmacologia , Animais , Proteínas de Transporte de Cátions/antagonistas & inibidores , Proteínas de Transporte de Cátions/deficiência , Proteínas de Transporte de Cátions/genética , Hipóxia Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Ativação Enzimática , Concentração de Íons de Hidrogênio , Hipertensão Pulmonar/enzimologia , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/fisiopatologia , Hipóxia/enzimologia , Hipóxia/patologia , Hipóxia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Músculo Liso Vascular/fisiopatologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Inibidores de Proteínas Quinases/farmacologia , Artéria Pulmonar/enzimologia , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Piridinas/farmacologia , Ratos Wistar , Transdução de Sinais , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Trocadores de Sódio-Hidrogênio/genética , Remodelação Vascular/efeitos dos fármacos
18.
Int J Pediatr ; 2013: 690432, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24348581

RESUMO

Neurofibromatosis-1 is the most common single gene disorder affecting 1 in 3000. In children, it is associated not only with physical features but also with attention and learning problems. Research has identified a downward shift in intellectual functioning as well, but to date, there are no published studies about the everyday adaptive behavior of children with NF1. In this study, parental reports of adaptive behavior of 61 children with NF1 ages 3 through 8 were compared to an unaffected contrast group (n = 55) that comprised siblings and community members. Significant group differences in adaptive skills were evident and were largely related to group differences in intellectual functioning. In a subsample of children with average-range intellectual functioning, group differences in parent-reported motor skills were apparent even after controlling statistically for group differences in intellectual functioning. The implications of the findings for the care of children with NF1 are discussed.

19.
J Appl Toxicol ; 32(8): 627-34, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22912977

RESUMO

Pentachlorophenol (PCP) is an organochlorine pesticide that decreases the tumor-cell killing (lytic) function of human natural killer (NK) cells. NK cells defend against tumor cells and virally infected cells. They bind to these targets, utilizing a variety of cell-surface proteins. This study examined concentrations of PCP that decrease lytic function for alteration of NK binding to tumor targets. Levels of PCP that caused loss of binding function were then examined for effects on expression of cell-surface proteins needed for binding. Exposure to 10 µM PCP for 24 h (which caused a greater than 70% loss of lytic function) decreased NK binding function (34.6%), and CD11a (21.7%) and CD56 (26.2%) cell-surface proteins. Both binding function and cell-surface proteins were decreased after longer exposures to lower concentrations of PCP. These data indicate that continuous exposures to PCP decreased binding function as well as cell-surface marker expression in NK cells and that these changes may in part explain the losses of lytic function seen with these exposures. PCP exposures have been shown to increase the incidence of blood and kidney cancers in humans. These data indicate that a possible explanation for this increased risk may be loss of NK lytic function, which is at least in part owing to the loss of the ability of the NK cell to bind to tumor cells. These data also indicate that lost binding function may be due to loss of important cell-surface proteins.


Assuntos
Poluentes Ambientais/toxicidade , Células Matadoras Naturais/efeitos dos fármacos , Pentaclorofenol/toxicidade , Praguicidas/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Células K562 , Células Matadoras Naturais/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo
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