Will Familial Hypercholesterolaemia Cohorts Hide Many More Lisosomal Acid Lipase Deficiency Patients?

Aims: Lisosomal Acid Lipase Deficiency (LALD), historical known as Cholesterol Ester Storage Disease (CESD), is an autosomal lisosomal storage recessive disorder and an unrecognized cause of dyslipidaemia. Mutations in LIPA gene are the underlying cause of LALD, being a mutation in the splice site of exon 8 the most common cause of the disease. Patients with LALD present dyslipidaemia and altered liver function. The aim of this work was to analyze LIPA gene in patients with unexplained dyslipidaemia.

Complex Congenital Heart Disease: The Influence of Prenatal Diagnosis

INTRODUCTION: Complex congenital heart disease is a group of severe conditions. Prenatal diagnosis has implications on morbidity and mortality for most severe conditions. The purpose of this work was to evaluate the influence of prenatal diagnosis and distance of residence and birth place to a reference center, on immediate morbidity and early mortality of complex congenital heart disease. MATERIAL AND METHODS: Retrospective study of complex congenital heart disease patients of our Hospital, born between 2007 and 2012. RESULTS: There were 126 patients born with complex congenital heart disease. In 95%, pregnancy was followed since the first trimester, with prenatal diagnosis in 42%. There was a statistically significant relation between birth place and prenatal diagnosis. Transposition of great arteries was the most frequent complex congenital heart disease (45.2%), followed by pulmonary atresia with ventricular septal defect (17.5%) and hypoplastic left ventricle (9.5%). Eighty-two patients (65.1%) had prostaglandin infusion and 38 (30.2%)were ventilated before an intervention. Surgery took place in the neonatal period in 73%. Actuarial survival rate at 30 days, 12 and 24 months was 85%, 80% and 75%, respectively. There was no statistically significant relation between prenatal diagnosis and mortality. DISCUSSION: Most patients with complex congenital heart disease did not have prenatal diagnosis. All cases with prenatal diagnosis were born in a tertiary center. Prenatal diagnosis did not influence significantly neonatal mortality, as already described in other studies with heterogeneous complex heart disease. CONCLUSION: prenatal diagnosis of complex congenital heart disease allowed an adequate referral. Most patients with complex congenital heart disease were not diagnosed prenatally. This data should be considered when planning prenatal diagnosis of congenital heart disease.

A new eosinophilic esophagitis (EoE)-like disease without tissue eosinophilia found in EoE Families

BACKGROUND Eosinophilic esophagitis (EoE) is a rapidly emerging, chronic inflammatory, genetically impacted disease of the esophagus, defined clinically by symptoms of esophageal dysfunction and, pathologically, by an eosinophil-predominant tissue infiltration. However, in four EoE-families, we have identified patients presenting with EoE-typical and corticosteroid-responsive symptoms, but without tissue eosinophilia. It was the aim of this study to clinically and immunologically characterize these patients with EoE-like disease. METHODS Five patients suffering from an EoE-like disease were evaluated with endoscopic, histologic, functional and quantitative immunohistologic examinations, and mRNA expression determination. RESULTS The frequency of first generation offspring of EoE-like disease patients affected by EoE or EoE-like disease was 40%. Immunofluorescence analysis confirmed an almost complete absence of eosinophils in the esophageal tissues of patients with EoE-like disease, but revealed a considerable T cell infiltration, comparable to EoE. In contrast to EoE, eotaxin-3 mRNA and protein were markedly reduced in EoE-like disease (P < 0.05). The mRNA expression levels of three selected EoE genes (eotaxin-3, MUC4 and CDH26) allowed to discriminate between EoE-like disease, EoE and normal epithelium. CONCLUSIONS Patients suffering from "EoE without eosinophilia" do not fulfill formally the diagnostic criteria for EoE. However, their clinical manifestation, immunohistology and gene-expression pattern, plus the fact that they bequeath EoE to their offspring, suggest a uniform underlying pathogenesis. Conventional EoE, with its prominent eosinophilia, therefore appears to be only one phenotype of a broader "inflammatory dysphagia syndrome" spectrum. In this light, the role of the eosinophils, the definition of EoE, and its diagnostic criteria must likely be reconsidered. This article is protected by copyright. All rights reserved.

Burden of heart disease and stroke in Illinois : mortality, morbidity and risk factors.

"February 2007"

Heart disease and stroke in Illinois : now is the time for public health action : 2007-2012 state plan.

"6/07"--Colophon.

Facts about-- women : heart disease and stroke.

Mode of access: Internet.

Closed-Loop Deep Brain Stimulation: Bidirectional Neuroprosthetics for Tremor and BCI

Thesis (Ph.D.)--University of Washington, 2016-06

Longitudinal relationships among overweight, life satisfaction, and aspirations in young women

Objective: This study investigated associations of overweight status and changes in overweight status over time with life satisfaction and future aspirations among a community sample of young women. Research Methods and Procedures: A total of 7865 young women, initially 18 to 23 years of age, completed two surveys that were 4 years apart. These women provided data on their future life aspirations in the areas of further education, work/career, marital status, and children, as well as their satisfaction with achievements to date in a number of life domains. Women reported their height and weight and their sociodemographic characteristics, including current socioeconomic status (occupation). Results: Young women's aspirations were cross-sectionally related to BMI category, such that obese women were less likely to aspire to further education, although this relationship seemed explained largely by current occupation. Even after adjusting for current occupation, young women who were obese were more dissatisfied with work/career/study, family relationships, partner relationships, and social activities. Weight status was also longitudinally associated with aspirations and life satisfaction. Women who were overweight or obese at both surveys were more likely than other women to aspire to other types of employment (including self-employed and unpaid work in the home) as opposed to full-time employment. They were also less likely to be satisfied with study or partner relationships. Women who resolved their overweight/obesity status were more likely to aspire to being childless than other women. Discussion: These results suggest that being overweight/obese may have a lasting effect on young women's life satisfaction and their future life aspirations.

Characterization of heat shock protein-specific T cells in atherosclerosis

A role for infection and inflammation in atherogenesis is widely accepted. Arterial endothelium has been shown to express heat shock protein 60 (HSP60) and, since human (hHSP60) and bacterial (GroEL) HSP60s are highly conserved, the immune response to bacteria may result in cross-reactivity, leading to endothelial damage and thus contribute to the pathogenesis of atherosclerosis. In this study, GroEL-specific T-cell lines from peripheral blood and GroEL-, hHSP60-, and Porphyromonas gingivalis-specific T-cell lines from atherosclerotic plaques were established and characterized in terms of their cross-reactive proliferative responses, cytokine and chemokine profiles, and T-cell receptor (TCR) V beta expression by flow cytometry. The cross-reactivity of several lines was demonstrated. The cytokine profiles of the artery T-cell lines specific for GroEL, hHSP60, and P. gingivalis demonstrated Th2 phenotype predominance in the CD4 subset and Tc0 phenotype predominance in the CD8 subset. A higher proportion of CD4 cells were positive for interferon-inducible protein 10 and RANTES, with low percentages of cells positive for monocyte chemoattractant protein 1 and macrophage inflammatory protein la, whereas a high percentage of CD8 cells expressed all four chemokines. Finally, there was overexpression of the TCR V beta 5.2 family in all lines. These cytokine, chemokine, and V beta profiles are similar to those demonstrated previously for P. gingivalis-specific lines established from periodontal disease patients. These results support the hypothesis that in some patients cross-reactivity of the immune response to bacterial HSPs, including those of periodontal pathogens, with arterial endothelial cells expressing hHSP60 may explain the apparent association between atherosclerosis and periodontal infection.

A population of HLA-DR+ immature cells accumulates in the blood dendritic cell compartment of patients with different types of cancer

Dendritic cell (DC) defects are an important component of immunosuppression in cancer. Here, we assessed whether cancer could affect circulating DC populations and its correlation with tumor progression. The blood DC compartment was evaluated in 136 patients with breast cancer, prostate cancer, and malignant glioma. Phenotypic, quantitative, and functional analyses were performed at various stages of disease. Patients had significantly fewer circulating myeloid (CD11c(+)) and plasmacytoid (CD123(+)) DC, and a concurrent accumulation of CD11c(-)CD123(-) immature cells that expressed high levels of HLA-DR+ immature cells (DR+IC). Although DR+IC exhibited a limited expression of markers ascribed to mature hematopoietic lineages, expression of HLA-DR, CD40, and CD86 suggested a role as antigen-presenting cells. Nevertheless, DR+IC had reduced capacity to capture antigens and elicited poor proliferation and interferon-gamma secretion by T-lymphocytes. Importantly, increased numbers of DR+IC correlated with disease status. Patients with metastatic breast cancer showed a larger number of DR+IC in the circulation than patients with local/nodal disease. Similarly, in patients with fully resected glioma, the proportion of DR+IC in the blood increased when evaluation indicated tumor recurrence. Reduction of blood DC correlating with accumulation of a population of immature cells with poor immunologic function may be associated with increased immunodeficiency observed in cancer.

Sibling relationships in adolescence: Learning and growing together

fit this article, I discuss the reasons for my interest in sibling relationships, and showcase studies on sibling relationships in adolescence carried out with my colleagues and students, in the context of the broader literature on sibling relationships. Our studies have focused on a number of important issues concerned with sibling relationships. First, I report on the associations between sibling relationships and other family relationships and the ways that the various family relationships affect each other. Second, I report a study of sibling relationships in the context of parental separation and divorce and show that sibling relationships in these families are more likely to be high in both warmth and hostility than is true for relationships in 2-parent families. Third, I report on several data sets showing an association between the quality of sibling relationships and adolescent adjustment and the link between differential parenting, adolescent adjustment, and the quality of the sibling relationship. Fourth, I report on a study of comparison and competition in sibling relationships and the associations between sibling relationship quality and reactions to being outperformed by a sibling. Finally, I discuss possible future directions for research on sibling relationships, including the importance of multimethod studies and a longitudinal perspective.

Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data

Background Our aim was to calculate the global burden of disease and risk factors for 2001, to examine regional trends from 1990 to 2001, and to provide a starting point for the analysis of the Disease Control Priorities Project (DCPP). Methods We calculated mortality, incidence, prevalence, and disability adjusted life years (DALYs) for 136 diseases and injuries, for seven income/geographic country groups. To assess trends, we re-estimated all-cause mortality for 1990 with the same methods as for 2001. We estimated mortality and disease burden attributable to 19 risk factors. Findings About 56 million people died in 2001. Of these, 10.6 million were children, 99% of whom lived in low-and-middle-income countries. More than half of child deaths in 2001 were attributable to acute respiratory infections, measles, diarrhoea, malaria, and HIV/AIDS. The ten leading diseases for global disease burden were perinatal conditions, lower respiratory infections, ischaemic heart disease, cerebrovascular disease, HIV/AIDS, diarrhoeal diseases, unipolar major depression, malaria, chronic obstructive pulmonary disease, and tuberculosis. There was a 20% reduction in global disease burden per head due to communicable, maternal, perinatal, and nutritional conditions between 1990 and 2001. Almost half the disease burden in low-and-middle-income countries is now from non-communicable diseases (disease burden per head in Sub-Saharan Africa and the low-and-middle-income countries of Europe and Central Asia increased between 1990 and 2001). Undernutrition remains the leading risk factor for health loss. An estimated 45% of global mortality and 36% of global disease burden are attributable to the joint hazardous effects of the 19 risk factors studied. Uncertainty in all-cause mortality estimates ranged from around 1% in high-income countries to 15-20% in Sub-Saharan Africa. Uncertainty was larger for mortality from specific diseases, and for incidence and prevalence of non-fatal outcomes. Interpretation Despite uncertainties about mortality and burden of disease estimates, our findings suggest that substantial gains in health have been achieved in most populations, countered by the HIV/AIDS epidemic in Sub-Saharan Africa and setbacks in adult mortality in countries of the former Soviet Union. our results on major disease, injury, and risk factor causes of loss of health, together with information on the cost-effectiveness of interventions, can assist in accelerating progress towards better health and reducing the persistent differentials in health between poor and rich countries.

Volumetric and areal bone mineral density measures are associated with cardiovascular disease in older men and women: The health, aging, and body composition study

The associations of volumetric (vBMD) and areal (aBMD) bone mineral density measures with prevalent cardiovascular disease (CVD) and subclinical peripheral arterial disease (PAD) were investigated in a cohort of older men and women enrolled in the Health, Aging, and Body Composition Study. Participants were 3,075 well-functioning white and black men and women (42% black, 51% women), aged 68-80 years. Total hip, femoral neck, and trochanter aBMD were measured using dual-energy X-ray absorptiometry. Quantitative computed tomography was used to evaluate spine trabecular, integral, and cortical vBMD measures in a subgroup (n = 1,489). Logistic regression was performed to examine associations of BMD measures with CVD and PAD. The prevalence of CVD (defined by coronary heart disease, PAD, cerebrovascular disease, or congestive heart failure) was 29.8%. Among participants without CVD, 10% had subclinical PAD (defined as ankle-arm index < 0.9). Spine vBMD measures were inversely associated with CVD in men (odds ratio of integral [ORintegral] = 1.34, 95% confidence interval [CI] 1.10-1.63; ORtrabecular = 1.25, 95% CI 1.02-1.53; ORcortical = 1.36, 95% CI 1.11-1.65). In women, for each standard deviation decrease in integral vBMD, cortical vBMD, or trochanter aBMD, the odds of CVD were significantly increased by 28%, 27%, and 22%, respectively. Total hip aBMD was associated with subclinical PAD in men (OR = 1.39, 95% CI 1.03-1.84) but not in women. All associations were independent of age and shared risk factors between BMD and CVD and were not influenced by inflammatory cytokines (interleukin-6 and tumor necrosis factors-alpha). In conclusion, our results provide further evidence for an inverse association between BMD and CVD in men and women. Future research should investigate common pathophysiological links for osteoporosis and CVD.