Early intervention in Portugal: study of professionals’ perceptions

Early intervention (EI) has been characterized by considerable advances in its domain, which has had great repercussions in the implementation of the family-centered approach. These changes have had implications in the practices and in the adoption and learning of new values that should be implemented in EI. This study evaluates the professional perspectives regarding familycentered practices in EI programs in Portugal. The results highlight the importance of effective collaboration and coordination between health, education, and social services and the importance of providing child and family support in a natural context. These results reinforce the need to invest in professional training to improve the quality of services offered to families in EI.Fundação para a Ciência e a Tecnologia (FCT) no âmbito do projecto PEst-OE/CED/UI1661/2014 do CIEd

KIAA0101 Is Overexpressed, and Promotes Growth and Invasion in Adrenal Cancer

Background: KIAA0101 is a proliferating cell nuclear antigen-associated factor that is overexpressed in some human malignancies. Adrenocortical neoplasm is one of the most common human neoplasms for which the molecular causes are poorly understood. Moreover, it is difficult to distinguish between localized benign and malignant adrenocortical tumors. For these reasons, we studied the expression, function and possible mechanism of dysregulation of KIAA0101 in human adrenocortical neoplasm. Methodology/Principal Findings: KIAA0101 mRNA and protein expression levels were determined in 112 adrenocortical tissue samples (21 normal adrenal cortex, 80 benign adrenocortical tumors, and 11 adrenocortical carcinoma (ACC). SiRNA knockdown was used to determine the functional role of KIAA0101 on cell proliferation, cell cycle, apoptosis, soft agar anchorage independent growth and invasion in the ACC cell line, NCI-H295R. In addition, we explored the mechanism of KIAA0101 dysregulation by examining the mutational status. KIAA0101 mRNA (9.7 fold) and protein expression were significantly higher in ACC (p,0.0001). KIAA0101 had sparse protein expression in only a few normal adrenal cortex samples, which was confined to adrenocortical progenitor cells. KIAA0101 expression levels were 84 % accurate for distinguishing between ACC and normal and benign adrenocortical tumor samples. Knockdown of KIAA0101 gene expression significantly decreased anchorage independent growth by 80 % and invasion by 60 % (p = 0.001; p = 0.006). W

2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS) : Document covering atherosclerotic disease of extracranial carotid and vertebral, mesenteric, renal, upper and lower extremity arteries

Endorsed by: the European Stroke Organization (ESO), The Task Force for the Diagnosis and Treatment of Peripheral Arterial Diseases of the European Society of Cardiology (ESC) and of the European Society for Vascular Surgery (ESVS)Peer reviewe

TLR Tolerance Reduces IFN-Alpha Production Despite Plasmacytoid Dendritic Cell Expansion and Anti-Nuclear Antibodies in NZB Bicongenic Mice

Genetic loci on New Zealand Black (NZB) chromosomes 1 and 13 play a significant role in the development of lupus-like autoimmune disease. We have previously shown that C57BL/6 (B6) congenic mice with homozygous NZB chromosome 1 (B6.NZBc1) or 13 (B6.NZBc13) intervals develop anti-nuclear antibodies and mild glomerulonephritis (GN), together with increased T and B cell activation. Here, we produced B6.NZBc1c13 bicongenic mice with both intervals, and demonstrate several novel phenotypes including: marked plasmacytoid and myeloid dendritic cell expansion, and elevated IgA production. Despite these changes, only minor increases in anti-nuclear antibody production were seen, and the severity of GN was reduced as compared to B6.NZBc1 mice. Although bicongenic mice had increased levels of baff and tnf-α mRNA in their spleens, the levels of IFN-α-induced gene expression were reduced. Splenocytes from bicongenic mice also demonstrated reduced secretion of IFN-α following TLR stimulation in vitro. This reduction was not due to inhibition by TNF-α and IL-10, or regulation by other cellular populations. Because pDC in bicongenic mice are chronically exposed to nuclear antigen-containing immune complexes in vivo, we examined whether repeated stimulation of mouse pDC with TLR ligands leads to impaired IFN-α production, a phenomenon termed TLR tolerance. Bone marrow pDC from both B6 and bicongenic mice demonstrated markedly inhibited secretion of IFN-α following repeated stimulation with a TLR9 ligand. Our findings suggest that the expansion of pDC and production of anti-nuclear antibodies need not be associated with increased IFN-α production and severe kidney disease, revealing additional complexity in the regulation of autoimmunity in systemic lupus erythematosus

A Sulfhydryl-Reactive Ruthenium (II) Complex and Its Conjugation to Protein G as a Universal Reagent for Fluorescent Immunoassays

To develop a fluorescent ruthenium complex for biosensing, we synthesized a novel sulfhydryl-reactive compound, 4-bromophenanthroline bis-2,2′-dipyridine Ruthenium bis (hexafluorophosphate). The synthesized Ru(II) complex was crosslinked with thiol-modified protein G to form a universal reagent for fluorescent immunoassays. The resulting Ru(II)-protein G conjugates were identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The emission peak wavelength of the Ru(II)-protein G conjugate was 602 nm at the excitation of 452 nm which is similar to the spectra of the Ru(II) complex, indicating that Ru(II)-protein G conjugates still remain the same fluorescence after conjugation. To test the usefulness of the conjugate for biosensing, immunoglobulin G (IgG) binding assay was conducted. The result showed that Ru(II)-protein G conjugates were capable of binding IgG and the more cross-linkers to modify protein G, the higher conjugation efficiency. To demonstrate the feasibility of Ru(II)-protein G conjugates for fluorescent immunoassays, the detection of recombinant histidine-tagged protein using the conjugates and anti-histidine antibody was developed. The results showed that the histidine-tagged protein was successfully detected with dose-response, indicating that Ru(II)-protein G conjugate is a useful universal fluorescent reagent for quantitative immunoassays

Analysing the Large Decline in Coronary Heart Disease Mortality in the Icelandic Population Aged 25-74 between the Years 1981 and 2006

BACKGROUND: Coronary heart disease (CHD) mortality rates have been decreasing in Iceland since the 1980s. We examined how much of the decrease between 1981 and 2006 could be attributed to medical and surgical treatments and how much to changes in cardiovascular risk factors. METHODOLOGY: The previously validated IMPACT CHD mortality model was applied to the Icelandic population. The data sources were official statistics, national quality registers, published trials and meta-analyses, clinical audits and a series of national population surveys. PRINCIPAL FINDINGS: Between 1981 and 2006, CHD mortality rates in Iceland decreased by 80% in men and women aged 25 to 74 years, which resulted in 295 fewer deaths in 2006 than if the 1981 rates had persisted. Incidence of myocardial infarction (MI) decreased by 66% and resulted in some 500 fewer incident MI cases per year, which is a major determinant of possible deaths from MI. Based on the IMPACT model approximately 73% (lower and upper bound estimates: 54%-93%) of the mortality decrease was attributable to risk factor reductions: cholesterol 32%; smoking 22%; systolic blood pressure 22%, and physical inactivity 5% with adverse trends for diabetes (-5%), and obesity (-4%). Approximately 25% (lower and upper bound estimates: 8%-40%) of the mortality decrease was attributable to treatments in individuals: secondary prevention 8%; heart failure treatments 6%; acute coronary syndrome treatments 5%; revascularisation 3%; hypertension treatments 2%, and statins 0.5%. CONCLUSIONS: Almost three quarters of the large CHD mortality decrease in Iceland between 1981 and 2006 was attributable to reductions in major cardiovascular risk factors in the population. These findings emphasize the value of a comprehensive prevention strategy that promotes tobacco control and a healthier diet to reduce incidence of MI and highlights the potential importance of effective, evidence based medical treatments

Serum Calcium Levels Are Associated with Novel Cardiometabolic Risk Factors in the Population-Based CoLaus Study

BACKGROUND: Associations of serum calcium levels with the metabolic syndrome and other novel cardio-metabolic risk factors not classically included in the metabolic syndrome, such as those involved in oxidative stress, are largely unexplored. We analyzed the association of albumin-corrected serum calcium levels with conventional and non-conventional cardio-metabolic risk factors in a general adult population. METHODOLOGY/PRINCIPAL FINDINGS: The CoLaus study is a population-based study including Caucasians from Lausanne, Switzerland. The metabolic syndrome was defined using the Adult Treatment Panel III criteria. Non-conventional cardio-metabolic risk factors considered included: fat mass, leptin, LDL particle size, apolipoprotein B, fasting insulin, adiponectin, ultrasensitive CRP, serum uric acid, homocysteine, and gamma-glutamyltransferase. We used adjusted standardized multivariable regression to compare the association of each cardio-metabolic risk factor with albumin-corrected serum calcium. We assessed associations of albumin-corrected serum calcium with the cumulative number of non-conventional cardio-metabolic risk factors. We analyzed 4,231 subjects aged 35 to 75 years. Corrected serum calcium increased with both the number of the metabolic syndrome components and the number of non-conventional cardio-metabolic risk factors, independently of the metabolic syndrome and BMI. Among conventional and non-conventional cardio-metabolic risk factors, the strongest positive associations were found for factors related to oxidative stress (uric acid, homocysteine and gamma-glutamyltransferase). Adiponectin had the strongest negative association with corrected serum calcium. CONCLUSIONS/SIGNIFICANCE: Serum calcium was associated with the metabolic syndrome and with non-conventional cardio-metabolic risk factors independently of the metabolic syndrome. Associations with uric acid, homocysteine and gamma-glutamyltransferase were the strongest. These novel findings suggest that serum calcium levels may be associated with cardiovascular risk via oxidative stress

Changes in Dietary Fat Intake and Projections for Coronary Heart Disease Mortality in Sweden: A Simulation Study.

OBJECTIVE: In Sweden, previous favourable trends in blood cholesterol levels have recently levelled off or even increased in some age groups since 2003, potentially reflecting changing fashions and attitudes towards dietary saturated fatty acids (SFA). We aimed to examine the potential effect of different SFA intake on future coronary heart disease (CHD) mortality in 2025. METHODS: We compared the effect on future CHD mortality of two different scenarios for fat intake a) daily SFA intake decreasing to 10 energy percent (E%), and b) daily SFA intake rising to 20 E%. We assumed that there would be moderate improvements in smoking (5%), salt intake (1g/day) and physical inactivity (5% decrease) to continue recent, positive trends. RESULTS: In the baseline scenario which assumed that recent mortality declines continue, approximately 5,975 CHD deaths might occur in year 2025. Anticipated improvements in smoking, dietary salt intake and physical activity, would result in some 380 (-6.4%) fewer deaths (235 in men and 145 in women). In combination with a mean SFA daily intake of 10 E%, a total of 810 (-14%) fewer deaths would occur in 2025 (535 in men and 275 in women). If the overall consumption of SFA rose to 20 E%, the expected mortality decline would be wiped out and approximately 20 (0.3%) additional deaths might occur. CONCLUSION: CHD mortality may increase as a result of unfavourable trends in diets rich in saturated fats resulting in increases in blood cholesterol levels. These could cancel out the favourable trends in salt intake, smoking and physical activity