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1.
Curr Urol Rep ; 19(7): 47, 2018 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-29774436

RESUMO

PURPOSE OF REVIEW: Men with spinal cord injury (SCI) commonly suffer from erectile dysfunction and ejaculatory dysfunction. The literature regarding the causes and treatment of these two important problems was reviewed. RECENT FINDINGS: Many of the erectile dysfunction treatments applied to able bodied individuals are also useful in the SCI population, although there are differences in the goals and results of treatment. Ejaculatory dysfunction can be treated with either penile vibratory stimulation or electroejaculation with high success rates. Pregnancies are possible, but poor quality sperm quality in male SCI patients leads to pregnancy rates lower than is observed in the able-bodied population. Although effective treatments are available for erectile and ejaculatory dysfunction in men with SCIs, many challenges remain in optimizing the treatment of these individuals.


Assuntos
Disfunção Erétil/terapia , Infertilidade Masculina/terapia , Traumatismos da Medula Espinal/complicações , Disfunção Erétil/etiologia , Humanos , Infertilidade Masculina/etiologia , Masculino
2.
Curr Urol Rep ; 18(11): 88, 2017 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-28921390

RESUMO

PURPOSE OF REVIEW: For many diseases that place a large burden on our health care system, men often have worse health outcomes than women. As the largest single provider of health care to men in the USA, the Veterans Health Administration (VA) has the potential to serve as leader in the delivery of improved men's health care to address these disparities. RECENT FINDINGS: The VA system has made recent strides in improving benefits for aspects of men's health that are traditionally poorly covered, such as treatment for male factor infertility. Despite this, review of Quality Enhancement Research Initiatives (QUERIs) within the VA system reveals few efforts to integrate disparate areas of care into a holistic men's health program. Policies to unify currently disparate aspects of men's health care will ensure that the VA remains a progressive model for other health care systems in the USA.


Assuntos
Prestação Integrada de Cuidados de Saúde/normas , Serviços de Saúde/normas , Saúde do Homem/normas , Melhoria de Qualidade , United States Department of Veterans Affairs/normas , Saúde dos Veteranos/normas , Prestação Integrada de Cuidados de Saúde/economia , Serviços de Saúde/economia , Saúde Holística/economia , Saúde Holística/normas , Humanos , Masculino , Saúde do Homem/economia , Melhoria de Qualidade/economia , Estados Unidos , United States Department of Veterans Affairs/economia , Saúde dos Veteranos/economia
3.
J Urol ; 194(6): 1601-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26100327

RESUMO

PURPOSE: MRF-TB (magnetic resonance imaging-ultrasound fusion targeted prostate biopsy) may improve the detection of prostate cancer in men presenting for prostate biopsy. We report clinical outcomes of 12-core systematic biopsy and MRF-TB in men who presented for primary biopsy and further describe pathological characteristics of cancers detected by systematic biopsy and not by MRF-TB. MATERIALS AND METHODS: Clinical outcomes of 452 consecutive men who underwent prebiopsy multiparametric magnetic resonance imaging followed by MRF-TB and systematic biopsy at our institution between June 2012 and June 2015 were captured in an institutional review board approved database. Clinical characteristics, biopsy results and magnetic resonance imaging suspicion scores were queried from the database. RESULTS: Prostate cancer was detected in 207 of 382 men (54.2%) with a mean±SD age of 64±8.5 years and mean±SEM prostate specific antigen 6.8±0.3 ng/ml who met study inclusion criteria. The cancer detection rate of systematic biopsy and MRF-TB was 49.2% and 43.5%, respectively (p=0.006). MRF-TB detected more Gleason score 7 or greater cancers than systematic biopsy (117 of 132 or 88.6% vs 102 of 132 or 77.3%, p=0.037). Of 41 cancers detected by systematic biopsy but not by MRF-TB 34 (82.9%) demonstrated Gleason 6 disease, and 26 (63.4%) and 34 (82.9%) were clinically insignificant by Epstein criteria and a UCSF CAPRA (University of California-San Francisco-Cancer of the Prostate Risk Assessment) score of 2 or less, respectively. CONCLUSIONS: In men presenting for primary prostate biopsy MRF-TB detects more high grade cancers than systematic biopsy. Most cancers detected by systematic biopsy and not by MRF-TB are at clinically low risk. Prebiopsy magnetic resonance imaging followed by MRF-TB decreases the detection of low risk cancers while significantly improving the detection and risk stratification of high grade disease.


Assuntos
Biópsia/estatística & dados numéricos , Imagem por Ressonância Magnética Intervencionista , Uso Excessivo dos Serviços de Saúde/estatística & dados numéricos , Imagem Multimodal , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/patologia , Medição de Risco/métodos , Ultrassonografia de Intervenção , Idoso , Biomarcadores Tumorais/sangue , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Próstata/patologia , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/epidemiologia , Sensibilidade e Especificidade , Revisão da Utilização de Recursos de Saúde
4.
Am J Drug Alcohol Abuse ; 40(6): 438-46, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25169838

RESUMO

OBJECTIVES: There is debate about whether marijuana (cannabis) use is more dangerous than alcohol use. Although difficult to make objective comparisons, research is needed to compare relative dangers in order to help inform preventive efforts and policy. METHODS: Data were analyzed from a nationally representative sample of high school seniors in the Monitoring the Future study (2007-2011; Weighted n = 7437; modal age: 18) who reported lifetime use of alcohol or marijuana. Students were asked to indicate whether they experienced various adverse psychosocial outcomes resulting from use of each substance. We examined which outcomes were more prevalent for each substance. RESULTS: Compared to alcohol use, marijuana use was more commonly reported to compromise relationships with teachers or supervisors, result in less energy or interest, and result in lower school or job performance. Compared to marijuana use, alcohol was more commonly reported to compromise relationships with friends and significant others; it was also reported to lead to more regret (particularly among females), and driving unsafely. Marijuana users were more likely to report no adverse outcomes. Females and white students were more likely to report various adverse outcomes and higher frequency use of each substance also increased occurrences of reported adverse outcomes. CONCLUSIONS: Marijuana and alcohol are associated with unique adverse psychosocial outcomes. Outcomes differ by sex and race/ethnicity, and perception or experience of outcomes may also be related to legal status and associated stigma. Public health interventions may be more effective by focusing on harm reduction strategies for these drug-specific outcomes.


Assuntos
Consumo de Bebidas Alcoólicas/efeitos adversos , Fumar Maconha/efeitos adversos , Estudantes/psicologia , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Condução de Veículo/estatística & dados numéricos , Coleta de Dados , Feminino , Humanos , Masculino , Fumar Maconha/epidemiologia , Fumar Maconha/psicologia , Prevalência , Fatores Sexuais , Estudantes/estatística & dados numéricos , Estados Unidos/epidemiologia , População Branca
5.
Ethn Dis ; 33(1): 26-32, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38846259

RESUMO

Introduction: Prostate cancer is the second leading cause of cancer deaths among men in the United States and harms Black men disproportionately. Most US men are uninformed about many key facts important to make an informed decision about prostate cancer. Most experts agree that it is important for men to learn about these problems as early as possible in their lifetime. Objectives: To compare the effect of a community health worker (CHW)-led educational session with a physician-led educational session that counsels Black men about the risks and benefits of prostate-specific antigen (PSA) screening. Methods: One hundred eighteen Black men recruited in 8 community-based settings attended a prostate cancer screening education session led by either a CHW or a physician. Participants completed surveys before and after the session to assess knowledge, decisional conflict, and perceptions about the intervention. Both arms used a decision aid that explains the benefits, risks, and controversies of PSA screening and decision coaching. Results: There was no significant difference in decisional conflict change by group: 24.31 physician led versus 30.64 CHW led (P=.31). The CHW-led group showed significantly greater improvement on knowledge after intervention, change (SD): 2.6 (2.81) versus 5.1 (3.19), P<.001). However, those in the physician-led group were more likely to agree that the speaker knew a lot about PSA testing (P<.001) and were more likely to trust the speaker (P<.001). Conclusions: CHW-led interventions can effectively assist Black men with complex health decision-making in community-based settings. This approach may improve prostate cancer knowledge and equally minimize decisional conflict compared with a physician-led intervention.


Assuntos
Negro ou Afro-Americano , Tomada de Decisões , Detecção Precoce de Câncer , Antígeno Prostático Específico , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/diagnóstico , Pessoa de Meia-Idade , Idoso , Antígeno Prostático Específico/sangue , Agentes Comunitários de Saúde , Médicos/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Estados Unidos
6.
Front Surg ; 8: 796876, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35028309

RESUMO

Introduction: The management of nephrolithiasis during pregnancy can be stressful for urologists due to concerns for investigations and treatments that may pose risk of fetal harm, and unfamiliarity with optimal management of these complex patients. In response, we created multi-disciplinary evidence-based guidelines to standardize the care for obstetric patients presenting with flank pain and suspicion for nephrolithiasis. Methods: A multi-disciplinary team involving Urology, Obstetric Anesthesiology, Obstetrics and Gynecology, Diagnostic Radiology, and Interventional Radiology from a single academic medical center was assembled. A PubMed search was performed using keywords of pregnancy/antepartum, nephrolithiasis/calculi/kidney stones, ureteroscopy, non-obstetric surgery, complications, preterm delivery, MRI, computerized tomography, renal bladder ultrasound (RBUS), and anesthesia to identify relevant articles. Team members reviewed their respective areas to create a comprehensive set of guidelines. One invited external expert reviewed the guidelines for validation purposes. Results: A total of 54 articles were reviewed for evidence synthesis. Four guideline statements were constructed to guide diagnosis and imaging, and seven statements to guide intervention. Guidelines were then used to create a diagnostic and intervention flowchart for ease of use. In summary, RBUS should be the initial diagnostic study. If diagnostic uncertainty still exists, a non-contrast CT scan should be obtained. For obstetric patients presenting with a septic obstructing stone, urgent decompression should be achieved. We recommend ureteral stent placement as the preferred intervention if local factors allow. Conclusions: We present a standardized care pathway for the management of nephrolithiasis during pregnancy. Our aim is to standardize and simplify the clinical management of these complex scenarios for urologists.

7.
Urology ; 144: 152-157, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32711010

RESUMO

OBJECTIVE: To develop and test the ability of a convolutional neural network (CNN) to accurately identify the presence of renal cell carcinoma (RCC) on histopathology specimens, as well as differentiate RCC histologic subtype and grade. MATERIALS AND METHODS: Digital hematoxylin and eosin stained biopsy images were downloaded from The Cancer Genome Atlas. A CNN model was trained on 100 um2 samples of either normal (3000 samples) or RCC (12,168 samples) tissue samples from 42 patients. RCC specimens included clear cell, chromophobe, and papillary histiotypes, as well as tissue of Fuhrman grades 1 through 4. Model testing was performed on an additional held-out cohort of benign and RCC specimens. Model performance was assessed on the basis of diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: The CNN model achieved an overall accuracy of 99.1% in the testing cohort for distinguishing normal parenchyma from RCC (sensitivity 100%, specificity 97.1%). Accuracy for distinguishing between clear cell, papillary, and chromophobehistiotypes was 97.5%. Accuracy for predicting Fuhrman grade was 98.4%. CONCLUSION: CNNs are able to rapidly and accurately identify the presence of RCC, distinguish RCC histologic subtypes, and identify tumor grade by analyzing histopathology specimens.


Assuntos
Carcinoma de Células Renais/diagnóstico , Aprendizado Profundo , Processamento de Imagem Assistida por Computador/métodos , Neoplasias Renais/diagnóstico , Rim/patologia , Carcinoma de Células Renais/patologia , Estudos de Coortes , Diagnóstico Diferencial , Humanos , Neoplasias Renais/patologia , Gradação de Tumores , Valor Preditivo dos Testes
8.
Urology ; 99: 174-179, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27562202

RESUMO

OBJECTIVE: To determine whether a combination of prostate cancer gene 3 (PCA3) and magnetic resonance imaging (MRI) suspicion score (mSS) could further optimize detection of prostate cancer on MRI fusion-targeted biopsy (MRF-TB) among men with no history of biopsy. MATERIALS AND METHODS: We included in this study 187 men presenting to our institution between June 2012 and August 2014 who underwent multiparametric MRI (mpMRI) and PCA3 before MRF-TB. Biopsy results, stratified by biopsy indication and PCA3 score, were recorded. Receiver operating characteristics curves and multivariable logistic regressions were used to model the association of PCA3 and mSS with cancer detection on MRF-TB. RESULTS: PCA3 is associated with cancer detection on MRF-TB for men with no prior biopsies (area under the curve: 0.67, 95% confidence interval: 0.59-0.76). Using a cutoff of ≥35, PCA3 was associated with cancer risk among men with mSS 2-3 (P = .004), but not among those with mSS 4-5 (P = .340). The interaction of PCA3 and mSS demonstrated significantly higher discrimination for cancer than mSS alone (area under the curve: 0.83 vs 0.79, P = .0434). CONCLUSION: Urinary PCA3 is associated with mSS and the detection of cancer on MRF-TB for men with no prior biopsies. PCA3 notably demonstrates a high negative predictive value among mSS 2-3. However, in the case of high-suspicion mpMRI, PCA3 is not associated with cancer detection on MRF-TB, adding little to cancer diagnosis. Further studies are needed to evaluate the utility of PCA3 in predicting cancer among men with normal mpMRI.


Assuntos
Antígenos de Neoplasias/urina , Biópsia Guiada por Imagem/métodos , Imagem por Ressonância Magnética Intervencionista/métodos , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico , Medição de Risco/métodos , Ultrassonografia de Intervenção/métodos , Biomarcadores Tumorais/urina , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , New York/epidemiologia , Valor Preditivo dos Testes , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/urina , Curva ROC
9.
Eur Urol ; 69(3): 512-7, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26112001

RESUMO

BACKGROUND: Increasing evidence supports the use of magnetic resonance imaging (MRI)-ultrasound fusion-targeted prostate biopsy (MRF-TB) to improve the detection of clinically significant prostate cancer (PCa) while limiting detection of indolent disease compared to systematic 12-core biopsy (SB). OBJECTIVE: To compare MRF-TB and SB results and investigate the relationship between biopsy outcomes and prebiopsy MRI. DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of a prospectively acquired cohort of men presenting for prostate biopsy over a 26-mo period. A total of 601 of 803 consecutively eligible men were included. INTERVENTIONS: All men were offered prebiopsy MRI and assigned a maximum MRI suspicion score (mSS). Men with an MRI abnormality underwent combined MRF-TB and SB. OUTCOMES: Detection rates for all PCa and high-grade PCa (Gleason score [GS] ≥7) were compared using the McNemar test. RESULTS AND LIMITATIONS: MRF-TB detected fewer GS 6 PCas (75 vs 121; p<0.001) and more GS ≥7 PCas (158 vs 117; p<0.001) than SB. Higher mSS was associated with higher detection of GS ≥7 PCa (p<0.001) but was not correlated with detection of GS 6 PCa. Prediction of GS ≥7 disease by mSS varied according to biopsy history. Compared to SB, MRF-TB identified more GS ≥7 PCas in men with no prior biopsy (88 vs 72; p=0.012), in men with a prior negative biopsy (28 vs 16; p=0.010), and in men with a prior cancer diagnosis (42 vs 29; p=0.043). MRF-TB detected fewer GS 6 PCas in men with no prior biopsy (32 vs 60; p<0.001) and men with prior cancer (30 vs 46; p=0.034). Limitations include the retrospective design and the potential for selection bias given a referral population. CONCLUSIONS: MRF-TB detects more high-grade PCas than SB while limiting detection of GS 6 PCa in men presenting for prostate biopsy. These findings suggest that prebiopsy multiparametric MRI and MRF-TB should be considered for all men undergoing prostate biopsy. In addition, mSS in conjunction with biopsy indications may ultimately help in identifying men at low risk of high-grade cancer for whom prostate biopsy may not be warranted. PATIENT SUMMARY: We examined how magnetic resonance imaging (MRI)-targeted prostate biopsy compares to traditional systematic biopsy in detecting prostate cancer among men with suspicion of prostate cancer. We found that MRI-targeted biopsy detected more high-grade cancers than systematic biopsy, and that MRI performed before biopsy can predict the risk of high-grade cancer.


Assuntos
Biópsia Guiada por Imagem/métodos , Imagem por Ressonância Magnética Intervencionista , Imageamento por Ressonância Magnética , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco
10.
Urology ; 85(5): 1130-1136, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25805522

RESUMO

OBJECTIVE: To determine the association between baseline factors, post-treatment factors, and long-term satisfaction after radical prostatectomy (RP). METHODS: Between January 2000 and March 2009, 1425 men who underwent RP by a single surgeon were enrolled in an institutional review board-approved, prospective, longitudinal outcomes study. Baseline characteristics and post-treatment functional and oncologic outcomes were captured through 2013. Patient survey responses from 875 (61.4%) of these men were used to evaluate satisfaction with treatment outcome and treatment decision. RESULTS: Overall, 88.2% and 91.0% men were satisfied to very satisfied with treatment outcome and treatment decision, respectively. Baseline sexual function was associated with satisfaction with both treatment outcome (adjusted odds ratio [aOR] = 1.40; 95% confidence interval [CI], 1.01-1.93) and treatment decision (aOR = 1.47; 95% CI, 1.08-2.01). Among post-treatment factors, higher University of California, Los Angeles Prostate Cancer Sexual Function (aOR = 2.95; 95% CI, 2.06-4.22), University of California, Los Angeles Prostate Cancer Urinary Function (aOR = 2.38; 95% CI, 1.66-3.40), and lower urinary tract symptom scores (aOR = 1.91; 95% CI, 1.19-3.06) were predictors of satisfaction with outcome. Bother due to incontinence and sexual dysfunction, and perception of cure were independent predictors of both satisfaction with treatment outcome and treatment decision. CONCLUSION: Nearly 90% of men are satisfied with both their treatment outcome and treatment decision after open RP. Improving long-term satisfaction after RP requires efforts to provide realistic expectations and improve functional outcomes.


Assuntos
Satisfação do Paciente , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
11.
Acad Med ; 90(12): 1713-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26308126

RESUMO

PURPOSE: In the United States, the prevalence of the use of alternative tobacco products (ATPs) (e.g., hookahs, e-cigarettes, cigars/cigarillos) has increased sharply. As future health care providers, medical students will play a critical role in health promotion and disease prevention. This study investigated medical students' use, knowledge, and beliefs about cigarettes and ATPs. METHOD: In 2014, the authors surveyed all students enrolled at one medical school in New York City. The survey included questions about personal use of tobacco products, perceptions about the harms of ATPs and their role in disease causation, education about ATPs, and cessation training and practices related to ATPs and cigarettes. The authors compared results across medical school classes. RESULTS: Of 720 students, 431 (59.9%) completed the survey. Of those, 64 (14.7%) were current users of tobacco or smoking products, including cigarettes (17; 3.9%), ATPs (21; 4.8%), or marijuana (39; 8.9%). Many believed that ATPs contributed less than cigarettes to various diseases. Respondents received less cessation training regarding ATPs than cigarettes (P < .0001). They felt less confident providing ATP cessation counseling than cigarette cessation counseling (P < .0001) and were less likely to report counseling patients on ATP cessation than cigarette cessation (46 [10.7%] versus 280 [64.8%], P < .0001). CONCLUSIONS: A concerning percentage of surveyed medical students use tobacco products, including ATPs, and lack the knowledge, education, and cessation counseling skills to provide accurate information about them to patients. ATP education should be added to medical school curricula to address this gap.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Nicotiana/efeitos adversos , Abandono do Hábito de Fumar/métodos , Fumar/epidemiologia , Estudantes de Medicina/psicologia , Estudos Transversais , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Feminino , Humanos , Masculino , Cidade de Nova Iorque , Faculdades de Medicina , Fumar/efeitos adversos , Abandono do Hábito de Fumar/psicologia , Adulto Jovem
12.
Urology ; 86(6): 1192-8, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26335497

RESUMO

OBJECTIVE: To report outcomes of magnetic resonance imaging (MRI)-ultrasound fusion-targeted biopsy (MRF-TB) and 12-core systematic biopsy (SB) over a 26-month period in men with prior negative prostate biopsy. MATERIALS AND METHODS: Between June 2012 and August 2014, 210 men presenting to our institution for prostate biopsy with ≥1 prior negative biopsy underwent multiparametric MRI followed by MRF-TB and SB and were entered into a prospective database. Clinical characteristics, maximum mpMRI suspicion scores (mSS), and biopsy results were queried from the database, and the detection rates of Gleason ≥7 prostate cancer (PCa) and overall PCa were compared between biopsy techniques using McNemar's test. RESULTS: Forty seven (29%) of 161 men meeting inclusion criteria (mean age, 65 ± 8 years; mean prostate-specific antigen, 8.9 ± 8.9) were found to have PCa. MRF-TB and SB had overall cancer detection rates (CDRs) of 21.7% and 18.6% (P = .36), respectively, and CDR for Gleason score (GS) ≥7 disease of 14.9% and 9.3% (P = .02), respectively. Of 26 men with GS ≥7 disease, MRF-TB detected 24 (92.3%) whereas SB detected 15 (57.7%; P < .01). Using UCSF-CAPRA criteria, only 1 man was restratified from low risk to higher risk based on SB results compared to MRF-TB alone. Among men with mSS <4, 72% of detected cancers were low risk by UCSF-CAPRA criteria. CONCLUSION: In men with previous negative biopsies and persistent suspicion of PCa, SB contributes little to the detection of GS ≥7 disease by MRF-TB, and avoidance of SB bears consideration. Based on the low likelihood of detecting GS ≥7 cancer and overall low-risk features of PCa in men with mSS <4, limiting biopsy to men with mSS ≥4 warrants further investigation.


Assuntos
Imagem por Ressonância Magnética Intervencionista , Próstata/diagnóstico por imagem , Próstata/patologia , Neoplasias da Próstata/patologia , Ultrassonografia de Intervenção , Idoso , Humanos , Biópsia Guiada por Imagem , Masculino , Pessoa de Meia-Idade , Imagem Multimodal , Gradação de Tumores , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Reoperação , Medição de Risco
13.
Mol Cell Biol ; 33(11): 2339-52, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23547260

RESUMO

hsa-miR-33a and hsa-miR-33b, intronic microRNAs (miRNAs) located within the sterol regulatory element-binding protein 2 and 1 genes (Srebp-2 and -1), respectively, have recently been shown to regulate lipid homeostasis in concert with their host genes. Although the functional role of miR-33a and -b has been highly investigated, the role of their passenger strands, miR-33a* and -b*, remains unclear. Here, we demonstrate that miR-33a* and -b* accumulate to steady-state levels in human, mouse, and nonhuman primate tissues and share a similar lipid metabolism target gene network as their sister strands. Analogous to miR-33, miR-33* represses key enzymes involved in cholesterol efflux (ABCA1 and NPC1), fatty acid metabolism (CROT and CPT1a), and insulin signaling (IRS2). Moreover, miR-33* also targets key transcriptional regulators of lipid metabolism, including SRC1, SRC3, NFYC, and RIP140. Importantly, inhibition of either miR-33 or miR-33* rescues target gene expression in cells overexpressing pre-miR-33. Consistent with this, overexpression of miR-33* reduces fatty acid oxidation in human hepatic cells. Altogether, these data support a regulatory role for the miRNA* species and suggest that miR-33 regulates lipid metabolism through both arms of the miR-33/miR-33* duplex.


Assuntos
Regulação da Expressão Gênica , Metabolismo dos Lipídeos/genética , MicroRNAs/genética , Regiões 3' não Traduzidas , Animais , Sequência de Bases , Linhagem Celular , Sequência Conservada , Ácidos Graxos/metabolismo , Humanos , Fígado/citologia , Fígado/fisiologia , Macaca mulatta/genética , Macrófagos/citologia , Macrófagos/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo
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