RESUMO
Autoreactive B cells have critical roles in a large diversity of autoimmune diseases, but the molecular pathways that control these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed microRNA library and identified miR-148a as a potent regulator of B cell tolerance. Elevated miR-148a expression impaired B cell tolerance by promoting the survival of immature B cells after engagement of the B cell antigen receptor by suppressing the expression of the autoimmune suppressor Gadd45α, the tumor suppressor PTEN and the pro-apoptotic protein Bim. Furthermore, increased expression of miR-148a, which occurs frequently in patients with lupus and lupus-prone mice, facilitated the development of lethal autoimmune disease in a mouse model of lupus. Our studies demonstrate a function for miR-148a as a regulator of B cell tolerance and autoimmunity.
Assuntos
Apoptose/genética , Autoimunidade/genética , Linfócitos B/imunologia , Tolerância Imunológica/genética , MicroRNAs/genética , Animais , Apoptose/imunologia , Proteínas Reguladoras de Apoptose/metabolismo , Autoimunidade/imunologia , Proteína 11 Semelhante a Bcl-2 , Transplante de Medula Óssea , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/genética , Modelos Animais de Doenças , Células HEK293 , Humanos , Tolerância Imunológica/imunologia , Immunoblotting , Lúpus Eritematoso Sistêmico/imunologia , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos MRL lpr , MicroRNAs/imunologia , Proteínas Nucleares/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de RNARESUMO
BACKGROUND/AIMS: Diabetic nephropathy (DN) is one of the complications of diabetes mellitus (DM). This study aimed to investigate the association between genetic polymorphisms, specifically AGTR1 (rs5186) and TGF-ß1 (rs1800470), and the risk of developing Diabetic nephropathy (DN) in type 2 diabetes mellitus patients, compared to those without DN and healthy controls. METHODS: A case-control study was conducted on 165 diabetic patients (59 with diabetic nephropathy (DN) and 54 without DN (DM)), and 52 healthy controls (HC). The genotyping was done using amplification refractory mutation system method (ARMS-PCR). Age, gender, and duration of diabetes were matched across groups. Clinical parameters including FBS, RBS, HbA1C, creatinine, urea, SBP, DBP, total cholesterol, triglycerides, LDL, and BMI were assessed. RESULTS: Diabetic patients with nephropathy exhibited significantly higher levels of clinical parameters compared to those without nephropathy and healthy controls. The risk allele of AGTR1 , C (p <0.0001), and risk allele containing genotypes AC (p <0.0001) and CC (p - 0.0010) were significantly higher in DN patients compared to DM and HC groups. Similarly, the TGF-ß1 risk allele C (p - 0.0001), and corresponding genotypes TC (p - 0.0038) and CC (p - 0.0027) were significantly associated with increased risk of diabetic nephropathy compared to DM and HC groups. CONCLUSION: The data showed significant association of AGTR1 (rs5186) and TGF-ß1 (rs1800470) polymorphism with an increased risk of diabetic nephropathy in type 2 diabetes mellitus patients. More investigation will be required to disseminate the results, while increasing the samples size and using whole genome sequencing.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Polimorfismo de Nucleotídeo Único , Receptor Tipo 1 de Angiotensina , Fator de Crescimento Transformador beta1 , Humanos , Nefropatias Diabéticas/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Fator de Crescimento Transformador beta1/genética , Pessoa de Meia-Idade , Estudos de Casos e Controles , Receptor Tipo 1 de Angiotensina/genética , Frequência do Gene , Alelos , Predisposição Genética para Doença , Genótipo , Idoso , AdultoRESUMO
BACKGROUND: Thyroid cancer, originating in the neck's thyroid gland, encompasses various types. Genetic mutations, particularly in BRAF and RET genes are crucial in its development. This study investigates the association between BRAF (rs113488022) and RET (rs77709286) polymorphisms and thyroid cancer risk in the Khyber Pakhtunkhwa (KP) population. METHODS: Blood samples from 100 thyroid cancer patients and 100 healthy controls were genotyped using ARMS-PCR followed by gel electrophoresis and statistical analysis. RESULTS: Analysis revealed a significant association between the minor allele T of BRAF (rs113488022) and thyroid cancer risk (P = 0.0001). Both genotypes of BRAF (rs113488022) showed significant associations with thyroid cancer risk (AT; P = 0.0012 and TT; P = 0.045). Conversely, the minor allele G of RET (rs77709286) exhibited a non-significant association with thyroid cancer risk (P = 0.2614), and neither genotype showed significant associations (CG; P = 0.317, GG; P = 0.651). Demographic and clinical parameters analysis using SPSS showed a non-significant association between BRAF and RET variants and age group (P = 0.878 and P = 0.536), gender (P = 0.587 and P = 0.21), tumor size (P = 0.796 and P = 0.765), or tumor localization (P = 0.689 and P = 0.727). CONCLUSION: In conclusion, this study emphasizes the significant association between BRAF polymorphism and thyroid cancer risk, while RET polymorphism showed a less pronounced impact. Further validation using larger and specific datasets is essential to establish conclusive results.
Assuntos
Proteínas Proto-Oncogênicas B-raf , Sulfonas , Neoplasias da Glândula Tireoide , Uridina/análogos & derivados , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genética , Alelos , Proteínas Proto-Oncogênicas c-ret/genéticaRESUMO
Sexual violence (SV) on college campuses disproportionately affects cisgender (nontransgender) women, sexual minorities (e.g., gays/lesbians, bisexuals), and gender minority (e.g., transgender/nonbinary) people. This study investigates gender and sexual behavior differences in common SV intervention targets-SV-related knowledge, prevention behaviors, and care-seeking. We analyzed cross-sectional survey data, collected in 9/2015-3/2017, from 2202 students aged 18-24 years attending college health and counseling centers at 28 Pennsylvania and West Virginia campuses. Multivariable multilevel models tested gender and sexual behavior differences in SV history; recognition of SV; prevention behaviors (self-efficacy to obtain sexual consent, intentions to intervene, positive bystander behaviors); and care-seeking behaviors (knowledge of, self-efficacy to use, and actual use of SV services). Adjusting for lifetime exposure to SV, compared with cisgender men, cisgender women had higher recognition of SV and reproductive coercion, prevention behaviors, and care-seeking self-efficacy (beta range 0.19-1.36) and gender minority people had higher recognition of SV and intentions to intervene (beta range 0.33-0.61). Cisgender men with any same-gender sexual partners had higher SV knowledge (beta = 0.23) and self-efficacy to use SV services (beta = 0.52) than cisgender men with only opposite-gender partners. SV history did not explain these differences. Populations most vulnerable to SV generally have higher SV knowledge, prevention behaviors, and care-seeking behaviors than cisgender men with only opposite-gender sexual partners. Innovative SV intervention approaches are necessary to increase SV-related knowledge among heterosexual cisgender men and may need to target alternative mechanisms to effectively reduce inequities for sexual and gender minority people.
Assuntos
Delitos Sexuais , Humanos , Masculino , Feminino , Adulto Jovem , Adolescente , Estudos Transversais , Delitos Sexuais/prevenção & controle , Comportamento Sexual , Conhecimentos, Atitudes e Prática em Saúde , Minorias Sexuais e de Gênero , Pennsylvania , West Virginia , Universidades , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
BACKGROUND: Single nucleotide polymorphism (SNPs) in BRCA1, BRCA2 and TP53 has been widely associated with breast cancer risk in different ethnicities with inconsistent results. There is no such study conducted so far in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. Therefore, this study was conducted to check BRCA1 (rs1799950), BRCA2 (rs144848) and TP53 (rs1042522) polymorphism with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan. METHODS: This study, consisting 140 breast cancer patients and 80 gender and age matched healthy controls were subjected to confirm BRCA1, BRCA2 and TP53 polymorphism. Clinicopathological data and blood samples were taken from all the participants. DNA was extracted and SNPs were confirmed using T-ARMS-PCR protocol. RESULTS: Our data indicated that BRCA1, BRCA2, and TP53 selected SNPs risk allele and risk allele containing genotypes displayed significant association (p < 0.05) with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. CONCLUSION: All the three selected SNPs of BRCA1, BRCA2 and TP53 showed significant association with breast cancer risk in the Pashtun population of Khyber Pakhtunkhwa, Pakistan. However, more investigation will be required on large data sets to confirm the selected SNPs and other SNPs in the selected and other related genes with the risk of breast cancer.
Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Predisposição Genética para Doença , Paquistão , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Proteína Supressora de Tumor p53/genética , Proteína BRCA1/genética , Proteína BRCA2/genéticaRESUMO
The accurate inheritance of genetic material is a basic necessity in all domains of life and an unexpectedly large number of RNA processing factors are required for mitotic progression and genome stability. NRDE2 (nuclear RNAi defective-2) is an evolutionarily conserved protein originally discovered for its role in nuclear RNA interference (RNAi) and heritable gene silencing in Caenorhabditis elegans (C. elegans). The function of the human NRDE2 gene remains poorly understood. Here we show that human NRDE2 is an essential protein required for suppressing intron retention in a subset of pre-mRNAs containing short, GC-rich introns with relatively weak 5' and 3' splice sites. NRDE2 preferentially interacts with components of the U5 small nuclear ribonucleoprotein (snRNP), the exon junction complex, and the RNA exosome. Interestingly, NRDE2-depleted cells exhibit greatly increased levels of genomic instability and DNA damage, as well as defects in centrosome maturation and mitotic progression. We identify the essential centriolar satellite protein, CEP131, as a direct NRDE2-regulated target. NRDE2 specifically binds to and promotes the efficient splicing of CEP131 pre-mRNA, and depleting NRDE2 dramatically reduces CEP131 protein expression, contributing to impaired recruitment of critical centrosomal proteins (e.g., γ-tubulin and Aurora Kinase A) to the spindle poles during mitosis. Our work establishes a conserved role for human NRDE2 in RNA splicing, characterizes the severe genomic instability phenotypes observed upon loss of NRDE2, and highlights the direct regulation of CEP131 splicing as one of multiple mechanisms through which such phenotypes might be explained.
Assuntos
Fatores de Processamento de RNA/metabolismo , Splicing de RNA , Proteínas de Ligação a RNA/metabolismo , Linhagem Celular , Regulação da Expressão Gênica , Humanos , Íntrons , Interferência de RNA , Precursores de RNA/genética , Precursores de RNA/metabolismo , RNA Interferente Pequeno/genéticaRESUMO
Black transgender women (BTW) in the United States experience disproportionate rates of HIV despite biomedical prevention interventions such as pre-exposure prophylaxis (PrEP) and non-occupational post-exposure prophylaxis (nPEP). Using a sample of 490 BTW collected from 2014 to 2017, bivariate, multivariable, and multinomial analyses were conducted to determine factors associated with awareness and use of PrEP and nPEP. BTW living with HIV were more aware of PrEP than HIV-negative BTW. Structural, demographic, and trans-specific factors (e.g., experiences of homelessness, violence, and current hormone use) related to HIV risk were associated with PrEP and nPEP awareness. PrEP use was associated with behavioral HIV risks (e.g., STI diagnosis, having an HIV-positive partner, and needle-sharing) and may demonstrate risk recognition among BTW. Knowing someone using PrEP was significantly positively associated with PrEP use. Development of guidelines for PrEP and nPEP use for BTW should leverage the strengths of guidelines for other populations, while also acknowledging the unique risks for this population.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Pessoas Transgênero , Negro ou Afro-Americano , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Profilaxia Pós-Exposição , Estados Unidos/epidemiologiaRESUMO
Intimate partner violence (IPV) impacts sexual minority adolescents at rates equal to or greater than the rate it impacts heterosexual adolescents. We investigated whether reports of physical and sexual IPV were less frequent in school jurisdictions with more affirming climates for lesbian, gay, bisexual, transgender, and queer (LGBTQ) students; and whether these associations varied for sexual orientation subgroups. We combined student-level data from the 2015 Youth Risk Behavior Surveys on demographics and experiences with physical and sexual IPV with jurisdiction-level data from the 2014 School Health Profiles on LGBTQ-affirming school climate. Multilevel logistic regression models examined associations between LGBTQ-affirming school climates and IPV. We stratified our data by sex and examined whether these associations differed by sexual orientation subgroups using cross-level interaction terms between school climate and sexual orientation (assessed via sexual identity and behavior). Sexual minority youth were more likely to report experiencing past-year physical and sexual IPV than their heterosexual counterparts. Attending schools with more LGBTQ-affirming climates reduced the likelihood of reporting physical IPV, but not sexual IPV, for female students. More LGBTQ-affirming school climates increased risk for sexual IPV among gay male students. Establishing LGBTQ-affirming school climates may reduce physical IPV for female students, but may have unintended consequences on sexual IPV prevalence for gay male students. More work is necessary to ensure that these climates are affirming for all sexual minority students and to address sexual violence prevention.
Assuntos
Bullying , Vítimas de Crime , Violência por Parceiro Íntimo , Cultura Organizacional , Minorias Sexuais e de Gênero , Adolescente , Bullying/prevenção & controle , Feminino , Humanos , Violência por Parceiro Íntimo/prevenção & controle , Masculino , Instituições AcadêmicasRESUMO
PURPOSE: Intraoperative assessment of distal radioulnar joint (DRUJ) alignment is often based on lateral radiographs whose interpretation is dependent upon positioning the forearm in neutral rotation. The dorsal tangential view (DTV) is a near-axial view of the dorsal wrist used in assessing dorsal screw penetration during radius fixation. The purpose of this study was to determine whether the DTV can also reliably assess DRUJ alignment in multiple forearm positions. METHODS: Four transhumeral cadaveric specimens were used to simulate an unstable DRUJ. The stabilizing soft tissue structures of the DRUJ were sectioned. Fluoroscopic DTV images were obtained with the DRUJ of each specimen held in 5 positions: dorsally dislocated, dorsally subluxated, reduced, volarly subluxated, and volarly dislocated. In each position, images were taken with the forearm in neutral rotation, full pronation, and full supination. Three observers independently assessed DRUJ position on DTV images. Intra- and interobserver reliability were assessed in each forearm position. RESULTS: Observers correctly identified DRUJ position as reduced, volarly malreduced, or dorsally malreduced on 94% of the DTV images (97%, 95%, and 92% in the neutral, supinated, and pronated forearm positions, respectively). Weighted kappa values for intraobserver reliability were 0.965, 0.964, and 0.965 for the 3 observers. The mean kappas for intraobserver reliability were 1.000, 0.967, and 0.930 with the forearm in neutral, supinated, and pronated positions, respectively. Weighted kappa values for interobserver reliability between paired observers were 0.948, 0.912, and 0.929. The mean kappa for interobserver reliability was 0.926, 0.931, and 0.930 for the forearm in neutral, supinated, and pronated positions, respectively. CONCLUSIONS: The DTV reliably demonstrated the position of the DRUJ independent of forearm rotation in a cadaveric model. CLINICAL RELEVANCE: Surgeons may consider the DTV as another tool for fluoroscopic verification of the DRUJ reduction in the operating room or clinic.
Assuntos
Instabilidade Articular , Fenômenos Biomecânicos , Cadáver , Antebraço/diagnóstico por imagem , Humanos , Instabilidade Articular/diagnóstico por imagem , Instabilidade Articular/cirurgia , Pronação , Rádio (Anatomia)/diagnóstico por imagem , Rádio (Anatomia)/cirurgia , Reprodutibilidade dos Testes , Supinação , Ulna , Articulação do Punho/diagnóstico por imagemRESUMO
PURPOSE: Racial and socioeconomic disparities have been reported in the management of appendicitis. Perforated appendicitis (PA) is used as an index for barriers to care due to delays in treatment. This study evaluates the effect of racial and socioeconomic differences on the likelihood of PA in a universally insured national healthcare system. METHODS: A retrospective review of pediatric patients enrolled in TRICARE who underwent appendectomy during a 5-year period was performed. Logistic regression was used to examine the association between ethnicity, age, gender, parent, or guardian marital status and deployment status of the active duty parent, type of facility, and type of admission with the odds of perforated appendicitis. RESULTS: A total of 3124 children met inclusion criteria. One-third of children carried the diagnosis of PA. Increased odds of PA was associated with younger age of patient among children of military personnel with enlisted ranks and senior officer ranks. CONCLUSION: In a universal healthcare system, no disparities across race with regard to presentation of appendicitis were identified. Increased odds of perforated appendicitis were observed in younger patients, but this was demonstrated in families of both high and low socioeconomic status. Universal coverage does appear to eliminate some barriers to healthcare.
Assuntos
Apendicectomia/métodos , Apendicite/cirurgia , Disparidades em Assistência à Saúde , Assistência de Saúde Universal , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos RetrospectivosRESUMO
Autoimmunity is largely prevented by medullary thymic epithelial cells (TECs) through their expression and presentation of tissue-specific Ags to developing thymocytes, resulting in deletion of self-reactive T cells and supporting regulatory T cell development. The transcription factor Prdm1 has been implicated in autoimmune diseases in humans through genome-wide association studies and in mice using cell type-specific deletion of Prdm1 in T and dendritic cells. In this article, we demonstrate that Prdm1 functions in TECs to prevent autoimmunity in mice. Prdm1 is expressed by a subset of mouse TECs, and conditional deletion of Prdm1 in either Keratin 14- or Foxn1-expressing cells in mice resulted in multisymptom autoimmune pathology. Notably, the development of Foxp3+ regulatory T cells occurs normally in the absence of Blimp1. Importantly, nude mice developed anti-nuclear Abs when transplanted with Prdm1 null TECs, but not wild-type TECs, indicating that Prdm1 functions in TECs to regulate autoantibody production. We show that Prdm1 acts independently of Aire, a crucial transcription factor implicated in medullary TEC function. Collectively, our data highlight a previously unrecognized role for Prdm1 in regulating thymic epithelial function.
Assuntos
Autoimunidade , Linfócitos T/imunologia , Timo/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Animais , Anticorpos Antinucleares/biossíntese , Anticorpos Antinucleares/imunologia , Autoanticorpos/biossíntese , Autoanticorpos/imunologia , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Células Epiteliais/fisiologia , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Queratina-14/genética , Queratina-14/metabolismo , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Fator 1 de Ligação ao Domínio I Regulador Positivo , Linfócitos T Reguladores/imunologia , Timo/citologia , Fatores de Transcrição/deficiência , Proteína AIRERESUMO
PURPOSE: Obesity and weight gain are associated with comorbidities including a higher risk of tumor recurrence and cancer-related deaths among breast cancer (BC) survivors; however, the underlying mechanisms linking obesity and cancer are poorly understood. Given the lack of clinically validated BC biomarkers, obesity and weight-loss studies utilize serum biomarkers as the intermediary outcomes of tumor recurrence. Studies have indicated microRNAs (miRNA)s are reliable biomarkers for cancer. We hypothesized that miRNA expression correlates with obesity and weight loss amongst BC survivors. This would yield insight into the biological pathways by which this association occurs, enabling more precise development of therapeutics. PATIENTS AND METHODS: We correlated baseline body mass index (BMI) with serum miRNA expression in 121 BC survivors enrolled in the Hormones and Physical Exercise (HOPE) trial. We then analyzed expression of the 35 most abundant miRNAs from HOPE in a six-month randomized controlled weight-loss trial (Lifestyle, Exercise, and Nutrition; LEAN) in 100 BC survivors. Ingenuity pathway analysis (IPA) software was used to identify biological pathway targets of the BMI-associated and intervention-responsive miRNAs using predictive biomarkers. RESULTS: Pearson correlations in HOPE identified eight miRNAs associated with BMI, including miR-191-5p (r = - 0.22, p = 0.016) and miR-122-5p (r = 0.25, p = 0.0048). In the LEAN validation study, levels of miR-191-5p significantly increased during the six-month intervention (p = 0.082). Ingenuity Pathway Analysis identified "Estrogen-mediated S-phase entry" (HOPE p = 0.003; LEAN p < 0.001) and "Molecular mechanisms of cancer" (HOPE p = 0.02; LEAN p < 0.001) as the top canonical pathways that significantly correlated with BMI-associated and intervention-responsive miRNAs and contain obesity and cancer-relevant genes including the E2F family of transcription factors and CCND1, which have been implicated in sporadic BC. CONCLUSION: While the association between obesity and BC recurrence and mortality has been demonstrated in the literature, mechanisms underlying the link between weight gain and cancer are unclear. Using two independent clinical trials, we identified novel miRNAs associative to BMI and weight loss that contribute to the development of cancer. Predictive modeling of miRNA targets identified multiple canonical pathways associated with cancer, highlighting potential mechanisms explaining the link between BMI and increased cancer risk.
Assuntos
Neoplasias da Mama/terapia , Exercício Físico/fisiologia , Recidiva Local de Neoplasia/prevenção & controle , Adulto , Idoso , Biomarcadores Tumorais/genética , Índice de Massa Corporal , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/fisiopatologia , Obesidade/complicações , Obesidade/fisiopatologia , Obesidade/terapia , Redução de PesoRESUMO
OBJECTIVES: We sought to calculate HIV incidence in a retrospective cohort of young (13-29â years old) black men who have sex with men (YBMSM) accessing repeated HIV-antibody testing in a mid-size city in the USA. METHODS: We aggregated site-specific HIV-antibody testing results from the project's inception among YBMSM who received an initial negative result and accessed at least one additional HIV-antibody test. From these data, we assessed number of seroconversions and person-years and calculated HIV incidence using a mid-P exact test to estimate 95% CIs. RESULTS: Five seroconversions were documented over 42.3 person-years (the mean age at first onsite test: 19.7â years), resulting in an HIV incidence rate of 11.8% (95% CI 4.3% to 26.2%). The mean age at seroconversion was 20.4 (±3.0)â years. CONCLUSIONS: Even in mid-size cities with low HIV prevalence rates in the general population, HIV incidence among YBMSM may be high. Community-based HIV-antibody testing organisations serving YBMSM should be encouraged and trained to track repeated HIV testing and calculate HIV incidence rates. Increased resources should be deployed to develop and encourage regular HIV testing in community health sites serving YBMSM.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Infecções por HIV/etnologia , Homossexualidade Masculina/estatística & dados numéricos , Adolescente , Adulto , Soropositividade para HIV/etnologia , Homossexualidade Masculina/etnologia , Humanos , Incidência , Masculino , Pennsylvania/epidemiologia , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: The dissection of the carotid sinus nerve in eversion carotid endarterectomy (eCEA) has been hypothesized to cause an increase in postoperative blood pressure (BP). The objective of this study is to evaluate the effect of eCEA on BP and changes in BP medications over the course of year-long follow-up after eCEA compared with longitudinal incision carotid endarterectomy patch angioplasty (pCEA). METHODS: A retrospective review of patients who underwent CEA between July 1, 2009 and June 30, 2014 in the Vascular Surgery Department at The University of Iowa Hospital and Clinics was conducted. Demographics, comorbidities, BP, and number, dosage, and type of antihypertensive medications were collected preoperatively, at 30 days, and at 12 months. The differences in BP and medications between pCEA and eCEA patients were compared. Demographic data and comorbidities were compared using t-tests and chi-squared analysis. Differences in BP and medication dosages were analyzed using multivariate analysis of variance. RESULTS: In total, 363 CEA procedures were performed during the study period, of which 275 procedures were included in the final analysis. Thirty percent of the patients underwent eCEA. Fifty-four percent of the patients who underwent eCEA and 60% of the patients who underwent pCEA were symptomatic. Thirty-day mortality was 1.4% and 12-month mortality was 6.4% for the entire population. No postoperative neurologic deficits, including stroke, were observed. Analysis of BP did not yield a significant difference among preoperative, 30-day, and 12-month follow-up measurements (P = 0.893). There was no significant change to the number and total daily dose of BP medications preoperatively, at 30 days, or at 12 months. CONCLUSIONS: There is no statistical difference in mortality, morbidity, and patency rates at 30 days and 12 months between pCEA and eCEA. eCEA is also not associated with long-term BP changes compared with pCEA.
Assuntos
Pressão Sanguínea , Doenças das Artérias Carótidas/cirurgia , Endarterectomia das Carótidas , Idoso , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/fisiopatologia , Distribuição de Qui-Quadrado , Comorbidade , Endarterectomia das Carótidas/efeitos adversos , Endarterectomia das Carótidas/mortalidade , Feminino , Hospitais Universitários , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertensão/fisiopatologia , Iowa , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
The topical treatment of nail fungal infections has been a focal point of nail research in the past few decades as it offers a much safer and focused alternative to conventional oral therapy. Although the current focus remains on exploring the ways of enhancing permeation through the formidable nail barrier, the understanding of the nail microstructure and composition is far from complete. This article reviews our current understanding of the nail microstructure, composition and diseases. A few of the parameters affecting the nail permeability and potential causes of the recurrence of fungal nail infection are also discussed.
Assuntos
Antifúngicos/farmacocinética , Unhas/metabolismo , Unhas/ultraestrutura , Onicomicose/tratamento farmacológico , Administração Tópica , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Humanos , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Unhas/química , Unhas/patologia , Onicomicose/metabolismo , Onicomicose/microbiologia , Onicomicose/patologia , PermeabilidadeRESUMO
INTRODUCTION: Mohs micrographic surgery (MMS) is successful and cost effective, but may be time consuming as patients are required to wait for final wound repair until margins are clear. We propose for selected cases the "Mohs and Close technique" (MCT), in which the defect is immediately repaired after tumor resection rather than waiting until margins are clear. METHODS: MCT was only performed on tumors that had clearly de ned borders, low risk histology, whose resulting defect after exci- sion required either a primary or partial closure, and whose repair wouldn't change to a different repair option if further stages of exci- sion were necessary. Tumor data was recorded for all cases. Time elapsed from tumor resection to completion of wound closure was recorded with and without performing MCT for comparable wounds. RESULTS: MCT was performed for 456 of 898 cases. Time required without MCT was significantly longer than with MCT when only one stage was performed (P<0.001). There was no statistical difference (P=0.3358) between the two separate techniques for cases which required 2 or more stages. CONCLUSION: MCT significantly reduces the time needed for selected Mohs cases that require only one stage of excision and therefore can increase the efficiency of MMS. J Drugs Dermatol. 2016;15(12):1481-1483.
Assuntos
Cirurgia de Mohs/métodos , Duração da Cirurgia , Neoplasias Cutâneas/cirurgia , Humanos , Neoplasias Cutâneas/diagnóstico , Resultado do TratamentoRESUMO
PURPOSE: Treatment options for failed total wrist arthroplasty include implant revision, resection arthroplasty, and arthrodesis. Variable results associated with different techniques have been reported for arthrodesis and the procedure has substantial technical challenges, including restoration of wrist height, obtaining stable fixation, and achieving bony fusion. This study evaluates the radiographic results of a surgical technique for conversion of a failed arthroplasty to an arthrodesis. METHODS: A retrospective chart and radiograph review was performed in 20 wrists in 18 patients in whom conversion to an arthrodesis was performed using a contoured cancellous femoral head structural allograft and a wrist arthrodesis plate. Supplemental demineralized bone matrix combined with corticocancellous allograft chips was also used in 15 wrists. Median age at arthrodesis was 61 years (range, 45-78 years), and median follow-up was 34 months (range, 4-71 months). RESULTS: Nineteen of 20 wrists fused following the index procedure at a median of 4 months (range, 3-7 months). Proximal plate loosening occurred in 1 wrist but the joint still fused at 6 months; a successful osteotomy and revision of screw fixation was done 2 years later to correct the deformity and hardware irritation in this case. Complications were otherwise limited to 1 superficial infection that resolved with intravenous antibiotics. CONCLUSIONS: This technique for conversion of a failed total wrist arthroplasty to a wrist arthrodesis is safe, effective, and versatile. Wrist deformity is corrected, wrist height can be restored, stable fixation is obtained, and a high rate of fusion is achieved despite filling large defects using structural cancellous allograft. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
Assuntos
Artrodese/métodos , Artroplastia de Substituição/efeitos adversos , Instabilidade Articular/cirurgia , Falha de Prótese , Amplitude de Movimento Articular/fisiologia , Articulação do Punho/cirurgia , Adulto , Idoso , Artroplastia de Substituição/métodos , Placas Ósseas , Parafusos Ósseos , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Instabilidade Articular/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Medição da Dor , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Prognóstico , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/fisiopatologiaRESUMO
BACKGROUND: Nodular melanoma is the most dangerous form of melanoma and often evades early detection. METHODS: We present a frequently traveling businessman whose nodular melanoma was detected by airport full body scanners. RESULTS: For about 20 flights over 2 months, the airport full body scanners singled out an area on his left lower leg for a pat-down. Dermatologic examination discovered a nodular melanoma in this area, and after surgical excision, the man traveled without incident. CONCLUSION: This case raises the possibility of using full body imaging in the detection of melanomas, especially of the nodular subtype. In its current form, full body scanning would most likely not be sensitive or specific enough to become a recommended screening tool. Nonetheless, for travelers with areas repeatedly singled out by the machines without a known justification, airport scanners could serve as incidental free screening for suspicious nodular lesions that should prompt dermatologist referral.