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1.
Soc Work Public Health ; 35(4): 137-151, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32479161

RESUMO

Best practice recommendations by the American Academy of Pediatrics support routine screening for developmental delays in early childhood, specifically at 18 and 24 months for Autism Spectrum Disorder (ASD). During this critical developmental period, early identification and intervention are associated with best outcomes for ASD. Pediatricians perform a critical role in the early recognition of ASD, which can co-exist with other disorders further complicating the diagnosis. However, little is known about the current screening practices in Mississippi. This study provides a unique view of Mississippi pediatricians' perspectives of barriers to routine ASD screening. The intent of this phenomenology study was to better understand current practices and potential barriers, for performing ASD screening at the 18 and 24 month well child visits, as perceived by a sample of Mississippi's pediatric providers. Data collected through key informant interviews were coded to identify commonalities and patterns in responses and aided in the identification of current practices and perceived barriers through qualitative analysis. Although there was increasing implementation of ASD screening by health care providers, routine screening was not consistently conducted. The results suggest a need for a screening tool embedded in the electronic health record for easy access and monitoring. Findings replicated prior studies and endorsed the relevance of barriers that exist in screening Mississippi's youngest population. Mississippi children are at risk of delayed ASD diagnosis if modifications cannot be made to support the clinical environment for pediatricians. ABBREVIATIONS: AAP: American Academy of Pediatrics; ASD: Autism Spectrum Disorder; EHR: Electronic Health Record; M-CHAT-R/F: Modified Checklist for Autism in Toddlers, Revised with Follow-Up; CAY: Center for Advancement of Youth; ABA: Applied Behavior Analysis.


Assuntos
Transtorno do Espectro Autista , Programas de Rastreamento , Transtorno do Espectro Autista/diagnóstico , Pré-Escolar , Humanos , Lactente , Mississippi
2.
PLoS One ; 13(1): e0186185, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29351293

RESUMO

Fibroblast growth factor receptor 1 (FGFR1) has been noted to be amplified in a variety of squamous cell carcinomas (SCCa) of the head, neck, and lung and increased copy number (CN) is a predictor of poor outcomes. FGFR1 is a therapeutic target for lung SCCa and inhibition therapy is currently in clinical trials. Absolute quantification of FGFR1 from formalin fixed paraffin embedded (FFPE) tissue of laryngeal SCCa was examined in this retrospective study. A droplet digital polymerase chain reaction (ddPCR) was used for absolute quantitation of the FGFR1 gene CN. Of the 74 samples analyzed, FGFR1 CN analysis revealed 54% of samples had CN greater than 2 copies/cell (1.8-2.2 copies/cell), and 38% had CN values greater than 3. The mean and standard deviation FGFR1 CN was 4.17 ± 1.46 CN for African American patients (n = 41) and 3.78 ±1.85 CN for Caucasian patients (n = 31). Further, 60.9% of specimens from African Americans demonstrated increased FGFR1 CN compared to 48.4% of Caucasians. Two SCCA samples from Native American demonstrated increased FGFR1 CN (4.19 and 3.01 CN). The level of FGFR1 amplification did not correlate with tumor stage, lymph node staging, or metastasis. In this population, the proportion of patient samples with an FGFR1 amplification was three times higher than in reported for SCCA of the head and neck. Further, increased FGFR1 CN was observed in two racial groups not previously reported: African Americans and Native Americans. However, FGFR1 amplification is not prognostic in laryngeal squamous cell carcinomas.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Laríngeas/genética , Reação em Cadeia da Polimerase/métodos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Negro ou Afro-Americano , Carcinoma de Células Escamosas/patologia , Interpretação Estatística de Dados , Feminino , Dosagem de Genes , Humanos , Neoplasias Laríngeas/patologia , Masculino , Análise de Sobrevida , População Branca
3.
J Pediatr Hematol Oncol ; 40(1): 51-55, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29200151

RESUMO

Acute chest syndrome (ACS) is a common and serious lung complication in sickle cell disease. A retrospective medical chart review was performed over a 6-year period in all pediatric ACS patients to investigate whether factors during the initial hospitalization were associated with recurrent ACS episodes. There were 386 episodes of ACS: 149 had only 1 episode of ACS, and 76 had >1 episode of ACS; 172 (76.4%) had hemoglobin SS, and 39 (17.3%) had hemoglobin SC. The most common presenting features were fever (83%), pain (70%), and cough (61%), which changed with the number of ACS episodes. Children <4 years old were at greatest risk of recurrent ACS (P=0.018). In addition, history of asthma (adjusted incident rate ratio [IRR]=1.52; 95% confidence interval [CI], 1.22-1.98; P<0.0001), shortness of breath (IRR, 1.29; 95% CI, 1.02-1.62; P=0.033), and length of hospital stay (IRR, 1.04; 95% CI, 1.01-1.08; P=0.017) were significantly associated with prospective ACS events. Multiple episodes of ACS are common in sickle cell disease, and certain risk factors during the initial hospitalization are associated with recurrent ACS.


Assuntos
Síndrome Torácica Aguda/etiologia , Anemia Falciforme/complicações , Síndrome Torácica Aguda/diagnóstico , Fatores Etários , Criança , Pré-Escolar , Tosse/etiologia , Dispneia , Feminino , Febre/etiologia , Humanos , Tempo de Internação , Masculino , Dor/etiologia , Recidiva , Estudos Retrospectivos , Fatores de Risco
4.
Complement Ther Med ; 32: 105-108, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28619294

RESUMO

AIMS: Mulberry leaves have been used anecdotally in Asia to treat many disease states, including glucose abnormalities. Animal and human studies illustrate potential benefit of mulberry leaf extract (MLE) in type 2 diabetes mellitus (DM2). The purpose of this study is to evaluate the glycemic and safety effects of MLE in patients with DM2. MATERIALS & METHODS: This randomized, double-blind, placebo-controlled pilot study evaluated MLE (1000mg standardized) versus matching placebo given three times daily with meals. Patients (n=24) were included if they had DM2 on single or combination oral therapy with a stable hemoglobin A1C (A1C). A 2-week placebo run-in (baseline) was followed by initiation of randomized medication for 3 months. Primary endpoints were change in A1C and self-monitoring blood glucoses (SMBG). Safety was also evaluated. RESULTS: Of 24 patients enrolled, 17 patients completed the study. Post-prandial SMBG was significantly decreased at 3 months in the MLE group versus baseline (16.1%; p<0.05). This improvement in post-prandial SMBG persisted when compared to placebo (18.2%; p<0.05). A1C decreased from 7.30% at baseline to 6.94% in the MLE group but did not reach statistical significance (p=0.079). There was no difference in A1C between MLE and placebo. A significant 15% increase occurred in serum creatinine when the MLE group was compared to baseline or placebo (p<0.05 for both). There was no significant effect on weight, fasting SMBG, blood pressure, hypoglycemia, or other safety evaluation markers. CONCLUSIONS: These results suggest that mulberry leaf extract may be a useful complementary mealtime glucose option for patients with DM2. ClinicalTrials.gov Identifier NCT00795704.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Morus , Extratos Vegetais/uso terapêutico , Glicemia/análise , Automonitorização da Glicemia , Feminino , Hemoglobinas Glicadas , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
5.
World J Gastroenterol ; 23(4): 638-645, 2017 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-28216970

RESUMO

AIM: To identify the predictors of vitamin D deficiency in patients with and without inflammatory bowel disease (IBD). METHODS: Patients with ulcerative colitis (UC) or Crohn's disease (CD) related diagnostic codes who received medical care at University of Mississippi Medical Center between July 2012 and 2015 were identified. After thorough chart review, we identified patients with biopsy proven IBD who had also been tested for serum 25-hydroxyvitamin D [25(OH)D] concentration. We compared these patients to a previously studied cohort of healthy controls who also had vitamin D concentration checked. Logistic regression analysis was performed to determine the association between vitamin d deficiency and UC, CD, race, age, gender and body mass index (BMI). RESULTS: We identified 237 patients with confirmed IBD. Of these, only 211 had a serum 25(OH)D concentrations available in the medical record. The group of healthy controls consisted of 98 individuals with available serum 25(OH)D concentration. 43% of IBD patients were African American (AA). Patients with CD were more likely to have vitamin D concentration checked. Bivariate analysis showed that AA (51% vs 21%, P = 0.00001), subjects with BMI >30 kg/m2 (39% vs 23% P = 0.01) and CD (40% vs 26%, P = 0.04) were more likely to be vitamin D deficient than vitamin D sufficient. Those with Age > 65 were more likely to be vitamin D sufficient (46% vs 15%, P = 0.04). Multiple regression showed that only BMI > 30 kg/m2 and AA race are associated with vitamin D deficiency. CONCLUSION: BMI > 30 kg/m2 and AA race are predictive of vitamin D deficiency. Gender, age and diagnosis of IBD are not predictive of vitamin D deficiency.


Assuntos
Colite Ulcerativa/complicações , Doença de Crohn/complicações , Deficiência de Vitamina D/complicações , Adulto , Negro ou Afro-Americano , Idoso , Biópsia , Índice de Massa Corporal , Estudos de Casos e Controles , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Razão de Chances , Projetos Piloto , Análise de Regressão , Estudos Retrospectivos , Estações do Ano , Vitamina D/análogos & derivados , Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia
6.
Prev Med ; 90: 216-22, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27473665

RESUMO

Physical inactivity is an independent risk factor for many diseases. Most research has focused on individual-level factors for physical activity (PA), but evidence suggests that neighborhood is also important. We examined baseline data collected between 2000 and 2004 from 5236 participants in the Jackson Heart Study to determine the effects of neighborhood on 2 types of PA: Active Living (AL), and Sports and Exercise (Sport) in an all-African American cohort. Participants were georeferenced and data from individual baseline questionnaires and US Census were analyzed using descriptive, bivariate, and multilevel models. In both types of PA, neighborhood factors had an independent and additive effect on AL and Sport. Living in an urban (p=0.003) or neighborhood with a higher percentage of residents with less than a high school education (p<0.001) was inversely associated with AL. There was an inverse interaction effect between individual and lower neighborhood education (p=0.01), as well as between age and urban neighborhoods (p=0.02) on AL. Individual level education (OR=1.30) and per capita income (OR=1.07) increased the odds of moderate-to-high sports. Future studies should focus on what contextual aspects of urban or less educated neighborhoods are influential in determining PA, as well as longitudinal multilevel analyses of neighborhood effects on PA.


Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Exercício Físico , Características de Residência/estatística & dados numéricos , Esportes , Estudos Transversais , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi , Estudos Prospectivos , Fatores de Risco , Fatores Socioeconômicos , Inquéritos e Questionários
7.
Am J Med Genet A ; 170(7): 1763-71, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27253440

RESUMO

Fetal alcohol spectrum disorders (FASD) comprise a range of physical differences and neurologic deficits from prenatal alcohol exposure. Previous studies suggest that relative maxillary growth deficiency can accompany FASD. Using the Fetal Alcohol Syndrome Epidemiologic Research (FASER) database, we investigated how maxillary and mandibular arcs and the ratio between them differ between FASD and non-FASD individuals. First, we established normative values for maxillary and mandibular arcs and maxillary-to-mandibular arc ratio. In our control group (545 males, 436 females), mean maxillary and mandibular arcs for males/females were 24.98/24.52 cm and 25.91/25.35 cm, respectively. The ratio was 0.9643 and 0.9676 for males and females, respectively. We then evaluated the effect of microcephaly, short stature, and low weight (<10th centile), individually on arcs in controls. Generally, arcs were reduced significantly but the ratio did not differ. We compared our controls to 138 male and 135 female FASD cases. We noted a significant difference in arcs in male and female groups, but not the ratio. We compared non-FAS controls with reduced growth parameters to similar cases with FASD. We did not find a significant difference in arc or ratio measurements. Therefore, we conclude the effect of prenatal alcohol exposure on maxillary and mandibular arc measurements is primarily on overall facial growth and less on asymmetric growth of the maxilla relative to the mandible, at least using this technique. © 2016 Wiley Periodicals, Inc.


Assuntos
Deficiências do Desenvolvimento/fisiopatologia , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Adolescente , Consumo de Bebidas Alcoólicas/efeitos adversos , Criança , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/epidemiologia , Feminino , Transtornos do Espectro Alcoólico Fetal/diagnóstico , Transtornos do Espectro Alcoólico Fetal/epidemiologia , Humanos , Masculino , Mandíbula/fisiopatologia , Troca Materno-Fetal , Maxila/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/diagnóstico , Efeitos Tardios da Exposição Pré-Natal/epidemiologia
8.
Am J Otolaryngol ; 37(3): 210-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27178510

RESUMO

IMPORTANCE: Resident fatigue has become a point of emphasis in medical education and its effects on otolaryngology residents and their patients require further study. OBJECTIVE: The purpose of our study was to evaluate the prevalence and nature of fatigue in otolaryngology residents, evaluate various quality of life measures, and investigate associations of increased fatigue with resident safety. STUDY DESIGN: Anonymous survey. SETTING: Internet based. PARTICIPANTS: United States allopathic otolaryngology residents. INTERVENTION: None. MAIN OUTCOME(S) AND MEASURES: The survey topics included demographics, residency structure, sleep habits and perceived stress. Responses were correlated with a concurrent Epworth Sleep Scale questionnaire to evaluate effects of fatigue on resident training and quality of life. RESULTS: 190 residents responded to the survey with 178 completing the Epworth Sleep Scale questionnaire. Results revealed a mean Epworth Sleep Scale score of 9.9±5.1 with a median of 10.0 indicating a significant number of otolaryngology residents are excessively sleepy. Statistically significant correlations between Epworth Sleep Scale and sex, region, hours of sleep, and work hours were found. Residents taking in-house call had significantly fewer hours of sleep compared to home call (p=0.01). Residents on "head and neck" (typically consisting of a large proportion of head and neck oncologic surgery) rotations tended to have higher Epworth Sleep Scale and had significantly fewer hours of sleep (p=.003) and greater work hours (p<.001). Additionally, residents who reported no needle stick type incidents or near motor vehicle accidents had significantly lower mean Epworth Sleep Scale scores. Only 37.6% of respondents approve of the most recent Accreditation Council for Graduate Medical Education work hour restrictions and 14% reported averaging greater than 80hours of work/week. CONCLUSION AND RELEVANCE: A substantial number of otolaryngology residents are excessively sleepy. Our data suggest that the effects of fatigue play a role in resident well-being and resident safety.


Assuntos
Fadiga/epidemiologia , Internato e Residência , Otolaringologia/educação , Adulto , Feminino , Humanos , Masculino , Qualidade de Vida , Segurança , Sono , Estresse Psicológico/epidemiologia , Inquéritos e Questionários , Estados Unidos
9.
Health Promot Pract ; 17(5): 711-21, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27095034

RESUMO

Trust in one's health care provider, trust in the health care system in general, and even trust in one's community affects engagement in HIV-related health care. This article examines the issue of trust among a random sample of HIV-infected individuals residing in Mississippi, an area hard-hit by the HIV/AIDS epidemic. Five constructs based on survey responses from these individuals were developed: (1) trust in one's provider to offer the best possible medical care, (2) trust in one's provider to protect patient privacy, (3) willingness to disclose HIV status to one's provider, (4) trust in the health care system, and (5) trust in one's community. Findings suggest that interventions to improve trust in providers to deliver the highest quality of care should be targeted to young people, African Americans, and the more highly educated. Interventions to increase trust in providers to protect privacy should focus on creating and strengthening social support groups or networks that build relationships and foster trust. Interventions aimed to increase community trust also should be targeted to young people. This information is useful to researchers, policy makers, health care providers, and organizations interested in prioritizing interventions and strategies that have the greatest potential to reduce health disparities in HIV diagnosis and treatment in the Deep South.


Assuntos
Infecções por HIV/etnologia , Infecções por HIV/psicologia , Relações Profissional-Paciente , Confiança , Síndrome da Imunodeficiência Adquirida/etnologia , Síndrome da Imunodeficiência Adquirida/psicologia , Adolescente , Adulto , Negro ou Afro-Americano/psicologia , Fatores Etários , Idoso , Confidencialidade , Estudos Transversais , Revelação , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Qualidade da Assistência à Saúde , Fatores Socioeconômicos , Adulto Jovem
10.
Brain Struct Funct ; 221(1): 171-84, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25287512

RESUMO

Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.


Assuntos
Complexo Nuclear Basolateral da Amígdala/patologia , Transtorno Depressivo Maior/patologia , Adolescente , Adulto , Idoso , Contagem de Células , Células Endoteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglia/patologia , Neurônios/patologia , Pericitos/patologia , Adulto Jovem
11.
Int Forum Allergy Rhinol ; 6(2): 140-2, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26290494

RESUMO

BACKGROUND: Saline nasal irrigations (SNI) are an important adjunct in the treatment of rhinosinusitis, and many patients prepare and store these solutions in their homes without an awareness of the potential for contamination. The objectives of this study were to determine if such contamination occurs and the effect of preparation methods on contamination. METHODS: Stock solutions of various tonicities and pHs were prepared using boiled, bottled, and distilled water (n = 57). The solutions were stored at ambient temperature or refrigerated for 1 week. Each day, 50 mL of the solutions were decanted to simulate transferring the stock solution into an irrigation vector. Cultures of the stock solutions were taken on days 1, 3, and 7. RESULTS: Overall contamination rate was 35.1%. The boiled water solutions were more likely to demonstrate bacterial growth (p < 0.001), as were those that were hypotonic (p = 0.046). pH had no significant effect (p = 0.127). Growth occurred as early as 24 hours after solution preparation. Pathogenic species isolated were Staphylococcus aureus, Moraxella sp, Sphingomonas paucimobilis, Acinetobacter junii, Methylobacterium sp, and Brevundimonas diminuta. No bacterial growth occurred in refrigerated solutions (p = 0.008). CONCLUSION: Pathogenic bacterial growth can occur in a short period of time in homemade SNI solutions with routine handling. Solutions should be refrigerated if possible. If solutions are to be stored at ambient temperature, they should be either isotonic or hypertonic and prepared from bottled or distilled water.


Assuntos
Infecções Bacterianas/prevenção & controle , Rinite/terapia , Sinusite/terapia , Cloreto de Sódio/uso terapêutico , Irrigação Terapêutica , Infecções Bacterianas/etiologia , Doença Crônica , Contaminação de Medicamentos , Serviços de Assistência Domiciliar , Humanos , Refrigeração , Cloreto de Sódio/análise , Irrigação Terapêutica/efeitos adversos
12.
Respir Care ; 60(5): 644-50, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25650437

RESUMO

BACKGROUND: The objective of this study was to determine whether the implementation of an inhaled nitric oxide protocol (INO) in a pediatric ICU (PICU) would reduce cost associated with its use without negatively affecting patient outcomes. METHODS: This is a retrospective cohort study of 76 subjects who required INO therapy in the PICU during the study period. A nitric oxide setup and weaning protocol was implemented in the PICU. The medical records of subjects who had received INO 18 months after protocol implementation, as well as the medical records of subjects who had received INO in the 18 months before protocol implementation, were reviewed. Length of time on INO, cost of INO per subject, mortality, stay, and ventilator hours were recorded. RESULTS: There were 38 subjects in the pre-protocol group and 38 subjects in the post-protocol group. There was a statistically significant decrease in the median per subject cost of INO between the pre- and post-protocol groups (P < .01). There was no statistically significant difference in the median duration of INO use (P = .06), median PICU (P = .42) or hospital (P = .58) stay, median duration of mechanical ventilation (P = .79) or percent mortality (P = .28) between the 2 groups. CONCLUSIONS: Implementation of an INO setup and weaning protocol in a PICU reduces the cost associated with its use without a statistically significant difference in mortality. In an era of increased awareness regarding healthcare spending, implementation of evidence-based protocols can provide a way to ensure the judicious utilization of medical resources.


Assuntos
Broncodilatadores/economia , Protocolos Clínicos/normas , Custos Diretos de Serviços/estatística & dados numéricos , Unidades de Terapia Intensiva Pediátrica/economia , Óxido Nítrico/economia , Administração por Inalação , Adolescente , Broncodilatadores/administração & dosagem , Criança , Pré-Escolar , Feminino , Mortalidade Hospitalar/tendências , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Pediátrica/normas , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Tempo de Internação , Masculino , Óxido Nítrico/administração & dosagem , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
13.
Alcohol Clin Exp Res ; 39(3): 476-84, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25704249

RESUMO

BACKGROUND: Brain cell death is a major pathological consequence of alcohol neurotoxicity. However, the molecular cascades in alcohol-induced brain tissue injury are unclear. METHODS: Using Western blot and double immunofluorescence, we examined the expression of interferon (IFN)-induced protein kinase R (PKR), phosphorylated-PKR (p-PKR), and IFN gamma (IFNγ) in the prefrontal cortex (PFC) of postmortem brains from subjects with alcohol use disorders (AUD). RESULTS: The protein levels of PKR, p-PKR, and IFNγ were significantly increased in subjects with AUD compared with control subjects without AUD, and a younger age of onset of AUD was significantly correlated with higher protein levels of p-PKR. In addition, elevated PKR- and p-PKR-IR were observed in both neurons and astrocytes in the PFC of subjects with AUD compared to subjects without AUD. CONCLUSIONS: The activation of the IFNγ-PKR pathway in PFC of humans is associated with chronic excessive ethanol use with an age of onset dependent manner, and activation of this pathway may play a pivotal role in AUD-related brain tissue injury. This study provides insight into neurodegenerative key factors related to AUD and identifies potential targets for the treatment of alcohol-induced neurotoxicity.


Assuntos
Transtornos Relacionados ao Uso de Álcool/metabolismo , Interferon gama/biossíntese , Córtex Pré-Frontal/metabolismo , Transdução de Sinais , eIF-2 Quinase/biossíntese , Adulto , Transtornos Relacionados ao Uso de Álcool/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/patologia , Transdução de Sinais/fisiologia
14.
Am Heart J ; 167(1): 116-122.e1, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24332150

RESUMO

BACKGROUND: African-American ancestry, hypokalemia, and QT interval prolongation on the electrocardiogram are all risk factors for sudden cardiac death (SCD), but their interactions remain to be characterized. SCN5A-1103Y is a common missense variant, of African ancestry, of the cardiac sodium channel gene. SCN5A-1103Y is known to interact with QT-prolonging factors to promote ventricular arrhythmias in persons at high risk for SCD, but its clinical impact in the general African-American population has not been established. METHODS: We genotyped SCN5A-S1103Y in 4,476 participants of the Jackson Heart Study, a population-based cohort of African Americans. We investigated the effect of SCN5A-1103Y, including interaction with hypokalemia, on QT interval prolongation, a widely-used indicator of prolonged myocardial repolarization and predisposition to SCD. We then evaluated the two sub-components of the QT interval: QRS duration and JT interval. RESULTS: The carrier frequency for SCN5A-1103Y was 15.4%. SCN5A-1103Y was associated with QT interval prolongation (2.7 milliseconds; P < .001) and potentiated the effect of hypokalemia on QT interval prolongation (14.6 milliseconds; P = .02). SCN5A-1103Y had opposing effects on the two sub-components of the QT interval, with shortening of QRS duration (-1.5 milliseconds; P = .001) and prolongation of the JT interval (3.4 milliseconds; P < .001). Hypokalemia was associated with diuretic use (78%; P < .001). CONCLUSIONS: SCN5A-1103Y potentiates the effect of hypokalemia on prolonging myocardial repolarization in the general African-American population. These findings have clinical implications for modification of QT prolonging factors, such as hypokalemia, in the 15% of African Americans who are carriers of SCN5A-1103Y.


Assuntos
Negro ou Afro-Americano/genética , Interação Gene-Ambiente , Sistema de Condução Cardíaco/fisiopatologia , Hipopotassemia/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Adulto , Idoso , Alelos , Morte Súbita Cardíaca , Eletrocardiografia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade
15.
Alcohol Clin Exp Res ; 38(1): 144-51, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23915421

RESUMO

BACKGROUND: The biochemical pathways underlying alcohol abuse and dependence are not well understood, although brain cell loss and neurotoxicity have been reported in subjects with alcohol dependence. Monoamine oxidase B (MAO B; an enzyme that catabolizes neurotransmitters such as dopamine) is consistently increased in this psychiatric illness. MAO B has been implicated in the pathogenesis of alcohol dependence and alcohol-induced brain neurotoxicity. Recently, the cell growth inhibitor protein, Kruppel-like factor 11 (KLF11), has been reported to be an MAO transcriptional activator. KLF11 is also known as TIEG2 (transforming growth factor-beta-inducible early gene 2) and mediates apoptotic cell death. This study investigates the protein expression of KLF11 and its relationship with MAO B using human postmortem prefrontal cortex from subjects with alcohol dependence. METHODS: Twelve subjects with alcohol dependence and the respective psychiatrically normal control subjects were investigated. Expression of KLF11 and MAO B proteins in the prefrontal cortex was measured by Western blot analysis. Correlation studies involving KLF11 and MAO B protein expression were performed. Localization of KLF11 in the human prefrontal cortex was also determined by immunohistochemistry. RESULTS: Levels of KLF11 protein were significantly increased by 44% (p < 0.03) in the postmortem prefrontal cortex of subjects with alcohol dependence as compared to age- and gender-matched, psychiatrically normal control subjects. Furthermore, KLF11 levels were significantly and positively correlated with both the increased MAO B protein levels and blood alcohol content in alcohol-dependent subjects. In addition, KLF11 protein expression was visualized in both neuronal and glial cells. CONCLUSIONS: This novel study shows the important role of KLF11, an MAO transcriptional activator, in human alcohol dependence. It further supports that the KLF11-MAO B cell death cascade may contribute to chronic alcohol-induced brain damage. This argues a case for KLF11-MAO B inhibition as a novel therapeutic strategy that may impact this highly prevalent illness.


Assuntos
Alcoolismo/metabolismo , Proteínas de Ciclo Celular/biossíntese , Regulação da Expressão Gênica , Monoaminoxidase/biossíntese , Córtex Pré-Frontal/metabolismo , Proteínas Repressoras/biossíntese , Ativação Transcricional/fisiologia , Alcoolismo/patologia , Proteínas Reguladoras de Apoptose , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/patologia , Estudos Retrospectivos
16.
Health Promot Pract ; 15(2): 189-98, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23945607

RESUMO

Using funds provided by the Ryan White Care Act, we conducted a statewide needs assessment of persons living with HIV/AIDS (PLWHA) in Mississippi as required by provisions of the Act. Most published research addressing access to care for PLWHA is based on convenience samples of persons already accessing care in specified clinic locations. For this study of a single state with a well-established mandatory reporting system, we conducted a cross-sectional study interviewing a random sample of PLWHA across the state of Mississippi. The Mississippi State Department of Health has maintained the Mississippi HIV/AIDS Reporting System since its inception in 1980. The database tracks all reported cases of HIV+ cases and includes name, age, last-known address, and other contact information. The sample was selected from a frame of all recorded PLWHA in Mississippi at that time, regardless of their association with care facilities. The purpose of this article is to describe the design and methodology of this study, difficulties encountered in locating this hard-to-reach population, multimethod recruiting strategies and outcomes, and lessons learned. Locating participants using a truly random sample from a mandatory reporting database was resource intensive. However, data collected as a result of these efforts have provided invaluable information on a number of topics important to PLWHA.


Assuntos
Bases de Dados Factuais , Sobreviventes de Longo Prazo ao HIV , Acessibilidade aos Serviços de Saúde , Notificação de Abuso , Seleção de Pacientes , Adolescente , Adulto , Idoso , Feminino , Promoção da Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi , Pesquisa Qualitativa , Adulto Jovem
17.
AIDS Care ; 25(1): 77-84, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22612404

RESUMO

The objective of this cross-sectional study was to describe the relationship between access to care and health-related quality of life (HRQOL) for persons living with HIV/AIDS (PLWHA) in Mississippi by administering a statewide survey. A random probability sample of PLWHA was derived from the Mississippi State Department of Health's communicable disease tracking system. Interviews were conducted with 220 PLWHA to collect data on access to care, demographic and social characteristics, and HRQOL. Overall, most participants had access to care and reasonable HRQOL. Multivariate and univariate analyses were performed to measure associations between access to care and HRQOL. Univariate analyses showed that age, income, social networks, severity of disease, having been prescribed medications, and having experienced problems accessing care to be significantly associated with HRQOL scales. Multivariate analysis of variance models further demonstrated low-income level, having experienced problems accessing care, and having been prescribed antiretroviral medications to be significantly associated with HRQOL. Reducing barriers is a major factor in improving quality of life. This study provides needed insight into the relationship between access to care and HRQOL among PLWHA in Mississippi, which could be valuable to public health planners to help them better understand how to make the greatest impact on HRQOL.


Assuntos
Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Acessibilidade aos Serviços de Saúde , Qualidade de Vida/psicologia , Adolescente , Adulto , Fatores Etários , Análise de Variância , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi/epidemiologia , Análise Multivariada , Índice de Gravidade de Doença , Fatores Sexuais , Estigma Social , Apoio Social , Fatores Socioeconômicos , Inquéritos e Questionários
18.
J Psychiatr Res ; 47(3): 299-306, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23201228

RESUMO

Neuroimaging consistently reveals smaller hippocampal volume in recurrent or chronic major depressive disorder (MDD). The underlying cellular correlates of the smaller volume are not clearly known. Postmortem tissues from 17 pairs of depressed and control subjects were obtained at autopsy, and informant-based retrospective psychiatric assessment was performed. Formalin-fixed left temporal lobes were sectioned (40 µm), stained for Nissl substance, and every 60th section selected throughout the entire hippocampus. Total volume of the hippocampal formation was calculated, and total numbers of pyramidal neurons (in hippocampal fields CA1, CA2/3, hilus), dentate gyrus (DG) granule cells, and glial cells were estimated stereologically. While hippocampal volume in all MDD subjects was not significantly smaller versus control subjects, in recurrent/chronic MDD, total volume decreased with duration of depressive illness (r = -0.696, p < 0.026). There was no significant difference between MDD and controls in total number or density of pyramidal neurons/granule cells or glial cells in CA1, CA2/3, hilus, or DG. However, CA1 pyramidal neuron density increased with duration of illness in recurrent/chronic MDD (r = 0.840, p < 0.002). Granule cell (r = 0.971, p < 0.002) and glial cell numbers (r = 0.980, p < 0.001) increased with age in those taking antidepressant medication (n = 6). Increasing DG granule cell and glial cell numbers with age in antidepressant-treated subjects may reflect proliferative effects of antidepressant medications. Decreasing total volume and increasing CA1 pyramidal neuron density with duration of illness in recurrent/chronic MDD lends support to the neuropil hypothesis of MDD.


Assuntos
Transtorno Depressivo Maior/patologia , Hipocampo/patologia , Neurônios/patologia , Contagem de Células , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Técnicas Estereotáxicas
19.
AIDS Care ; 25(8): 973-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23252519

RESUMO

A statewide needs assessment of persons living with HIV/AIDS (PLWHA) was conducted to determine what is known about access to care, utilization of services, and perceived barriers to receiving care and services. Our objective was to determine which needs were being met or unmet among PLWHA in Mississippi to provide a better understanding of how effectively to allocate funding to provide for the needs of that group. In this cross-sectional study, a true random sample of PLWHA in Mississippi was interviewed in 2005-2006. Questions were asked to identify opinions about respondents' experiences with 23 health care services and 30 public or private assistance services. The kappa statistic was used to measure agreement between level of services needed and level of services provided. Services with the lowest kappa scores revealed which services were being either mostly unmet, or even overly met. Greatest service needs were HIV viral load test, Pap smear, CD4/T-cell count test, and medication for HIV/AIDS, which were reasonably well met. The most significantly unmet needs were dental care and dental exams, eye care and eye exams, help paying for housing, subsidized housing assistance, mental health therapy or counseling, access to emotional support groups, and job placement or employment. Overly met services included medical care at a physician's office or clinic and free condoms. This study identified needs perceived to be significantly unmet by PLWHA, as well as areas that were perceived to be adequately or overly met. This information may be used to target areas with the greatest impact for improvement and provide insight into how to effectively allocate health care resources and public/private assistance.


Assuntos
Infecções por HIV/tratamento farmacológico , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Necessidades e Demandas de Serviços de Saúde/estatística & dados numéricos , Síndrome da Imunodeficiência Adquirida/terapia , Adolescente , Adulto , Distribuição por Idade , Idoso , Fármacos Anti-HIV/uso terapêutico , Serviços de Saúde Comunitária/estatística & dados numéricos , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mississippi , Serviços Preventivos de Saúde/normas , Serviços Preventivos de Saúde/estatística & dados numéricos , Adulto Jovem
20.
Artigo em Inglês | MEDLINE | ID: mdl-23261523

RESUMO

Dysregulation of the glutamatergic system has been implicated not only in the treatment of major depressive disorder (MDD), but also in the excitotoxic effects of stress and anxiety on the prefrontal cortex, which may precede the onset of a depressive episode. Our previous studies demonstrate marked deficits in prominent postsynaptic proteins involved in glutamate neurotransmission in the prefrontal cortex (PFC), Brodmann's area 10 (BA 10) from subjects diagnosed with major depressive disorder (MDD). In the same group of subjects we have identified deficits in expression and phosphorylation level of key components of the mammalian target of rapamycin (mTOR) signaling pathway, known to regulate translation initiation. Based on our previous findings, we have postulated that glutamate-dependent dysregulation of mTOR-initiated protein synthesis in the PFC may underlie the pathology of MDD. The aim of this study was to use the NanoString nCounter System to perform analysis of genes coding for glutamate transporters, glutamate metabolizing enzymes, neurotrophic factors and other intracellular signaling markers involved in glutamate signaling that were not previously investigated by our group in the PFC BA 10 from subjects with MDD. We have analyzed a total of 200 genes from 16 subjects with MDD and 16 healthy controls. These are part of the same cohort used in our previous studies. Setting our cutoff p-value≤0.01, marked upregulation of genes coding for mitochondrial glutamate carrier (GC1; p=0.0015), neuropilin 1 (NRP-1; p=0.0019), glutamate receptor ionotropic N-methyl-d-aspartate-associated protein 1 (GRINA; p=0.0060), and fibroblast growth factor receptor 1 (FGFR-1; p=0.010) was identified. No significant differences in expression of the remaining 196 genes were observed between MDD subjects and controls. While upregulation of FGFR-1 has been previously shown in MDD; abnormalities in GC-1, GRINA, and NRP-1 have not been reported. Therefore, this postmortem study identifies GC1, GRINA, and NRP-1 as novel factors associated with MDD; however, future studies will be needed to address the significance of these genes in the pathophysiology of depression and antidepressant activity.


Assuntos
Transtorno Depressivo Maior/genética , Expressão Gênica/fisiologia , Córtex Pré-Frontal/metabolismo , Adulto , Idoso , Intoxicação Alcoólica/complicações , Química Encefálica/fisiologia , Cadáver , Interpretação Estatística de Dados , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Ácido Glutâmico/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA/biossíntese , RNA/isolamento & purificação , Transdução de Sinais/fisiologia , Fumar/efeitos adversos , Serina-Treonina Quinases TOR/genética
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