A Comparison of the Liver Fat Score and CT Liver-to-Spleen Ratio as Predictors of Fatty Liver Disease by HIV Serostatus.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is common among HIV-infected (HIV+) adults. The Liver Fat Score (LFS) is a non-invasive, rapid, inexpensive diagnostic tool that uses routine clinical data and is validated against biopsy in HIV-uninfected (HIV-) persons. CT liver-to-spleen (L/S) attenuation ratio is another validated method to diagnose NAFLD. We compared NAFLD prevalence using the LFS versus L/S ratio among Multicenter AIDS Cohort Study participants to assess the LFS's performance in HIV+vs. HIV-men. METHODS: In a cross-sectional analysis of men reporting<3 alcoholic drinks daily (308 HIV+, 218 HIV-), Spearman correlations determined relationships between LFS and L/S ratio by HIV serostatus. Multivariable regression determined factors associated with discordance in LFS- and L/S ratio-defined NAFLD prevalence. RESULTS: NAFLD prevalence by LFS and L/S ratio were 28%/15% for HIV+men and 20%/19% for HIV-men, respectively. Correlations between LFS and L/S ratio were weaker among HIV+than HIV-men, but improved with increasing BMI and exclusion of HCV-infected men. LFS and L/S ratio discordance occurred more frequently and across BMI strata among HIV+men, but predominantly at BMI<30 kg/m2 among HIV-men. In multivariate analysis, only lower total testosterone levels were significantly associated with discordance. CONCLUSION: NAFLD prevalence was similar by LFS and L/S ratio identification among HIV-men, but dissimilar and with frequent discordance between the two tests among HIV+men. As discordance may be multifactorial, biopsy data are needed to determine the best non-invasive diagnostic test for NAFLD in HIV+persons.

Clinical history and management recommendations of the smooth muscle dysfunction syndrome due to ACTA2 arginine 179 alterations.

PURPOSE: Smooth muscle dysfunction syndrome (SMDS) due to heterozygous ACTA2 arginine 179 alterations is characterized by patent ductus arteriosus, vasculopathy (aneurysm and occlusive lesions), pulmonary arterial hypertension, and other complications in smooth muscle-dependent organs. We sought to define the clinical history of SMDS to develop recommendations for evaluation and management. METHODS: Medical records of 33 patients with SMDS (median age 12 years) were abstracted and analyzed. RESULTS: All patients had congenital mydriasis and related pupillary abnormalities at birth and presented in infancy with a patent ductus arteriosus or aortopulmonary window. Patients had cerebrovascular disease characterized by small vessel disease (hyperintense periventricular white matter lesions; 95%), intracranial artery stenosis (77%), ischemic strokes (27%), and seizures (18%). Twelve (36%) patients had thoracic aortic aneurysm repair or dissection at median age of 14 years and aortic disease was fully penetrant by the age of 25 years. Three (9%) patients had axillary artery aneurysms complicated by thromboembolic episodes. Nine patients died between the ages of 0.5 and 32 years due to aortic, pulmonary, or stroke complications, or unknown causes. CONCLUSION: Based on these data, recommendations are provided for the surveillance and management of SMDS to help prevent early-onset life-threatening complications.

Loss-of-Function Mutations in YY1AP1 Lead to Grange Syndrome and a Fibromuscular Dysplasia-Like Vascular Disease.

Fibromuscular dysplasia (FMD) is a heterogeneous group of non-atherosclerotic and non-inflammatory arterial diseases that primarily involves the renal and cerebrovascular arteries. Grange syndrome is an autosomal-recessive condition characterized by severe and early-onset vascular disease similar to FMD and variable penetrance of brachydactyly, syndactyly, bone fragility, and learning disabilities. Exome-sequencing analysis of DNA from three affected siblings with Grange syndrome identified compound heterozygous nonsense variants in YY1AP1, and homozygous nonsense or frameshift YY1AP1 variants were subsequently identified in additional unrelated probands with Grange syndrome. YY1AP1 encodes yin yang 1 (YY1)-associated protein 1 and is an activator of the YY1 transcription factor. We determined that YY1AP1 localizes to the nucleus and is a component of the INO80 chromatin remodeling complex, which is responsible for transcriptional regulation, DNA repair, and replication. Molecular studies revealed that loss of YY1AP1 in vascular smooth muscle cells leads to cell cycle arrest with decreased proliferation and increased levels of the cell cycle regulator p21/WAF/CDKN1A and disrupts TGF-ß-driven differentiation of smooth muscle cells. Identification of YY1AP1 mutations as a cause of FMD indicates that this condition can result from underlying genetic variants that significantly alter the phenotype of vascular smooth muscle cells.

Capacity of AIDS service organisations in Connecticut to respond to intimate partner violence.

Although intimate partner violence (IPV) is prevalent among women living with HIV and negatively impacts their health, few studies have examined the ability of AIDS service organisations (ASOs) to address IPV. This study used a qualitative approach to identify facilitators of and barriers to addressing IPV in female clients of ASOs in the United States. In-depth interviews were conducted between March and August 2011 with 20 ASO staff members and 19 female clients who reported a current or past history of IPV. Interviews were audio recorded, transcribed and analysed using the constant comparative method. These data identify barriers to addressing IPV at the organisation, provider and client levels, and include suggestions from both clients and providers about improving access to care. Client and provider suggestions differed in some areas. While providers emphasised structural changes such as increased training on IPV provided by their organisation, clients highlighted the importance of trusting personal relationships with staff to increase client disclosure of IPV experiences. Given the differing opinions of clients and staff, ASOs should consider involving women with histories of IPV in the process of programme and policy development. ASOs have the unique opportunity to provide comprehensive and holistic care by addressing IPV. The extent to which ASOs are able to recognise and address IPV and strategies for increasing this ability warrant greater attention from funders, ASO administrators and researchers.

Precision medical and surgical management for thoracic aortic aneurysms and acute aortic dissections based on the causative mutant gene.

Almost one-quarter of patients presenting with thoracic aortic aneurysms (TAAs) or acute aortic dissections (TAADs) have an underlying mutation in a specific gene. A subset of these patients will have systemic syndromic features, for example, skeletal features in patients with Marfan Syndrome. It is important to note that the majority of patients with thoracic aortic disease will not have these syndromic features but many will have a family history of the disease. The genes predisposing to these thoracic aortic diseases are inherited in an autosomal dominant manner, and thirteen genes have been identified to date. As the clinical phenotype associated with each specific gene is defined, the data indicate that the underlying gene dictates associated syndromic features. More importantly, the underlying gene also dictates the aortic disease presentation, the risk for dissection at a given range of aortic diameters, the risk for additional vascular diseases and what specific vascular diseases occur associated with the gene. These results lead to the recommendation that the medical and surgical management of these patients be dictated by the underlying gene, and for patients with mutations in ACTA2, the specific mutation in the gene.

Exploración del malestar emocional expresado por mujeres que acuden a centros de atención primaria de la Ciudad de México: Un estudio cualitativo / Exploring the emotional distress of women who attend primary health care units in Mexico City: A qualitative study

La presencia de malestar emocional -que se define como el conjunto de sensaciones subjetivas que percibe una persona de que su bienestar sufre una merma y que se manifiesta por síntomas inespecíficos- puede constituir un factor de riesgo para la aparición de enfermedades mentales, sobre todo en personas con vulnerabilidades biológicas y psicosociales. Estudios recientes señalan que los servicios de atención primaria reciben un número, cada vez mayor, de personas con malestares que no cubren los criterios diagnósticos de una enfermedad, ya sea mental o física, fenómeno que es más frecuente en las mujeres. El objetivo de este trabajo es analizar los malestares emocionales de un grupo de mujeres que acude a instituciones de atención primaria de la Ciudad de México, así como sus percepciones y vivencias sobre la atención recibida, con el propósito de identificar necesidades de atención. Para recopilar la información se utilizaron técnicas e instrumentos propios de la metodología cualitativa. La información se codificó y analizó conforme al método de "categorización de significados" propuesto por Kvale. Los resultados mostraron que los principales detonantes de los malestares emocionales en las participantes se asocian con las preocupaciones que enfrentan cotidianamente (como falta de dinero, problemas con los hijos y violencia intrafamiliar) y, en otros casos, con la vivencia de experiencias traumáticas de violencia y abuso sexual, pasadas y presentes. Los datos demuestran también que las mujeres no hablan directamente de su malestar emocional, pero que tampoco lo detecta el personal de salud o que, cuando lo hace, le resta importancia. Lo anterior se relaciona con las condiciones actuales del servicio, que no ofrece una atención integral y adolece de una visión psicosocial.

Emotional distress is the subjective sensation of diminishment in well-being which manifests itself in a number of unspecific symptoms. It might be a risk factor for the development of mental illness, especially among individuals with psychosocial or biological vulnerability. Recent studies show that primary health care services receive a growing number of patients who suffer distress, but do not fulfill the diagnostic criteria of a mental or physical illness. This phenomenon is more frequent among women. The objective of this paper is to analyze the emotional distress experienced by a group of women who attended primary health care institutions in Mexico City, as well as their perceptions and experiences around the attention received, in order to identify their treatment needs. Data was gathered through techniques and instruments pertaining qualitative methodology. The information was coded and analyzed according to the meaning categorization method developed by Kvale. The results show that the main triggers of emotional distress are associated to daily life worries (lack of money, problems with children, domestic violence, among others). In some cases, it is associated as well with traumatic events, such as violence and sexual abuse in the past or at present. Data also suggest that women do not talk about emotional distress directly during medical consultations and that health care professionals do not identify distress or minimize its importance. These aspects are related to the current characteristics of the service, which lacks a comprehensive approach and a psychosocial point of view.

Genotype in BRCA-associated breast cancers.

Women with BRCA1 or 2 mutations are at high risk for breast cancer. For BRCA1, a trend of increasing risk has been associated with increasing downstream (3') location for mutations compared to the upstream (5') mutations in the gene. For BRCA2, an increased risk of breast cancer has been associated with mutations outside of the ovarian cancer cluster region (OCCR). We sought to determine the mutation position in BRCA-associated breast cancers and whether or not there was a genotype-phenotype correlation. Breast cancer patients with BRCA1/2 mutations were identified by a search of a prospectively maintained data base. Mutation site, patient, and tumor characteristics were determined through retrospective review. One hundred and sixty-four patients with BRCA1-associated breast cancer and 109 patients with BRCA2-associated breast cancer were identified. Among patients with BRCA1-associated cancers, 86 (52%) had mutations in the 5' half of the gene. Among patients with BRCA2-associated breast cancers, 40 (37%) had OCCR mutations. Although BRCA1-associated tumors were more likely to be ER/PR- than BRCA2-associated cancers (p < 0.0001), there was no difference in the tumor characteristics among BRCA1 or BRCA2-associated cancers based on mutation location. In this single-institution study, over half of BRCA1-associated and over a third of BRCA2-associated breast cancers were associated with putative lower risk mutations. Although we cannot exclude the possibility that mutations in these regions confer a lower relative risk for breast cancer, vigilance in cancer screening and prevention remains necessary. Further studies in genotype/phenotype correlation are needed to individualize prevention strategies.