Juvenile Dermatomyositis Forty Years On: Case Report

We present a case report of a 42 year old female, diagnosed at the age of 3 with Juvenile Dermatomyositis. The clinical course was severe and refractory to immunosuppressive therapy. Currently, she is mostly affected by severe muscle atrophy, large joint contractures, calcinosis, and a lipodystrophy associated metabolic syndrome with hypertriglyceridemia, insulin resistance, high total testosterone and hepatic steatosis. She developed Hodgkin´s lymphoma in the course of her disease. Personalized therapeutic choices are discussed as regards juvenile dermatomyositis complications.info:eu-repo/semantics/publishedVersio

Structural and biophysical insights into the mode of covalent binding of rationally designed potent BMX inhibitors.

The bone marrow tyrosine kinase in chromosome X (BMX) is pursued as a drug target because of its role in various pathophysiological processes. We designed BMX covalent inhibitors with single-digit nanomolar potency with unexploited topological pharmacophore patterns. Importantly, we reveal the first X-ray crystal structure of covalently inhibited BMX at Cys496, which displays key interactions with Lys445, responsible for hampering ATP catalysis and the DFG-out-like motif, typical of an inactive conformation. Molecular dynamic simulations also showed this interaction for two ligand/BMX complexes. Kinome selectivity profiling showed that the most potent compound is the strongest binder, displays intracellular target engagement in BMX-transfected cells with two-digit nanomolar inhibitory potency, and leads to BMX degradation PC3 in cells. The new inhibitors displayed anti-proliferative effects in androgen-receptor positive prostate cancer cells that where further increased when combined with known inhibitors of related signaling pathways, such as PI3K, AKT and Androgen Receptor. We expect these findings to guide development of new selective BMX therapeutic approaches

Burden, coping, physical symptoms and psychological morbidity in caregivers of functionally dependent family members

Objectives: this study assessed burden, coping, physical symptoms and psychological morbidity in caregivers of functionally dependent family members. Methods: fifty family caregivers completed self-reported measures of burden, physical symptoms, psychological morbidity and coping strategies. Results: there was a significant negative correlation between coping strategies and the different clinical variables, as well as a significant positive correlation between coping strategies and duration of care. It appears that the stronger bond between caregiver and family member leads to a poorer use of adaptive coping strategies. It also appears that the deterioration of the relationship between them and the lower perceived self-efficacy are more prominente in caregivers of family members with cognitive impairment, indicating that caregivers with family members without cognitive impairment face fewer difficulties. Conclusion: these results emphasize the need for interventions to include coping strategies, since they are important in reducing caregivers’ burden, psychological morbidity and physical symptoms

Patterns of Cognitive Performance in Healthy Ageing in Northern Portugal: A Cross-Sectional Analysis

Background: The Minho Integrative Neuroscience Database (MIND)-Ageing project aims to identify predictors of healthy cognitive ageing, including socio-demographic factors. In this exploratory analysis we sought to establish baseline cohorts for longitudinal assessment of age-related changes in cognition. Methods: The population sample (472 individuals) was strictly a convenient one, but similar to the Portuguese population in the age profile. Participants older than 55 years of age were included if they did not present defined disabling pathologies or dementia. A standardized clinical interview was conducted to assess medical history and a battery of neuropsychological tests was administered to characterize global cognition (Mini Mental State Examination), memory and executive functions (Selective Reminding Test; Stroop Color and Word Test; and Block Design subtest of the Wechsler Adult Intelligence Scale). Cross-sectional analysis of the neuropsychological performance with individual characteristics such as age, gender, educational level and setting (retirement home, senior university, day care center or community), allowed the establishment of baseline clusters for subsequent longitudinal studies. Results: Based on different socio-demographic characteristics, four main clusters that group distinctive patterns of cognitive performance were identified. The type of institution where the elders were sampled from, together with the level of formal education, were the major hierarchal factors for individual distribution in the four clusters. Of notice, education seems to delay the cognitive decline that is associated with age in all clusters. Conclusions: Social-inclusion/engagement and education seem to have a protective effect on mental ageing, although this effect may not be effective in the eldest elders

Does dietary calcium interact with dietary fiber against colorectal cancer? : a case-control study in Central Europe

BACKGROUND: An unfavorable trend of increasing rates of colorectal cancer has been observed across modern societies. In general, dietary factors are understood to be responsible for up to 70% of the disease’s incidence, though there are still many inconsistencies regarding the impact of specific dietary items. Among the dietary minerals, calcium intake may play a crucial role in the prevention. The purpose of this study was to assess the effect of intake of higher levels of dietary calcium on the risk of developing of colorectal cancer, and to evaluate dose dependent effect and to investigate possible effect modification. METHODS: A hospital based case–control study of 1556 patients (703 histologically confirmed colon and rectal incident cases and 853 hospital-based controls) was performed between 2000–2012 in Krakow, Poland. The 148-item semi-quantitative Food Frequency Questionnaire to assess dietary habits and level of nutrients intake was used. Data regarding possible covariates was also collected. RESULTS: After adjustment for age, gender, education, consumption of fruits, raw and cooked vegetables, fish, and alcohol, as well as for intake of fiber, vitamin C, dietary iron, lifetime recreational physical activity, BMI, smoking status, and taking mineral supplements, an increase in the consumption of calcium was associated with the decrease of colon cancer risk (OR = 0.93, 95% CI: 0.89-0.98 for every 100 mg Ca/day increase). Subjects consumed >1000 mg/day showed 46% decrease of colon cancer risk (OR = 0.54, 95% CI: 0.35-0.83). The effect of dietary calcium was modified by dietary fiber (p for interaction =0.015). Finally, consistent decrease of colon cancer risk was observed across increasing levels of dietary calcium and fiber intake. These relationships were not proved for rectal cancer. CONCLUSIONS: The study confirmed the effect of high doses of dietary calcium against the risk of colon cancer development. This relationship was observed across different levels of dietary fiber, and the beneficial effect of dietary calcium depended on the level of dietary fiber suggesting modification effect of calcium and fiber. Further efforts are needed to confirm this association, and also across higher levels of dietary fiber intake

Socioeconomic Inequalities in the Prevalence of Nine Established Cardiovascular Risk Factors in a Southern European Population

The evaluation of the gender-specific prevalence of cardiovascular risk factors across socioeconomic position (SEP) categories may unravel mechanisms involved in the development of coronary heart disease. Using a sample of 1704 community dwellers of a Portuguese urban center aged 40 years or older, assessed in 1999–2003, we quantified the age-standardized prevalence of nine established cardiovascular risk factors (diabetes mellitus, hypertension, hypercholesterolemia, smoking, sedentariness, abdominal obesity, poor diet, excessive alcohol intake and depression) across SEP and gender categories. Data on individual education and occupation were collected by questionnaire and used to characterize SEP. The prevalence of seven out of nine well-established risk factors was higher in men. Among women, the prevalence of most of the studied risk factors was higher in lower SEP groups. The main exception was smoking, which increased with education and occupation levels. Among men, socioeconomic gradients were less clear, but lower SEP was associated with a higher prevalence of diabetes, excessive alcohol intake and depression in a graded mode. The historical cultural beliefs and practices captured throughout the lifecourse frame the wide socioeconomic gradients discernible in our study conducted in an unequal European developed population. While men were more exposed to most risk factors, the clearer associations between SEP and risk factors among women support that their adoption of particular healthy behaviors is more dependent on material and symbolic conditions. To fully address the issue of health inequalities, interventions within the health systems should be complemented with population-based policies specifically designed to reduce socioeconomic gradients

Evaluation of Group Genetic Ancestry of Populations from Philadelphia and Dakar in the Context of Sex-Biased Admixture in the Americas

Population history can be reflected in group genetic ancestry, where genomic variation captured by the mitochondrial DNA (mtDNA) and non-recombining portion of the Y chromosome (NRY) can separate female- and male-specific admixture processes. Genetic ancestry may influence genetic association studies due to differences in individual admixture within recently admixed populations like African Americans.We evaluated the genetic ancestry of Senegalese as well as European Americans and African Americans from Philadelphia. Senegalese mtDNA consisted of approximately 12% U haplotypes (U6 and U5b1b haplotypes, common in North Africa) while the NRY haplotypes belonged solely to haplogroup E. In Philadelphia, we observed varying degrees of admixture. While African Americans have 9-10% mtDNAs and approximately 31% NRYs of European origin, these results are not mirrored in the mtDNA/NRY pools of European Americans: they have less than 7% mtDNAs and less than 2% NRYs from non-European sources. Additionally, there is <2% Native American contribution to Philadelphian African American ancestry and the admixture from combined mtDNA/NRY estimates is consistent with the admixture derived from autosomal genetic data. To further dissect these estimates, we have analyzed our samples in the context of different demographic groups in the Americas.We found that sex-biased admixture in African-derived populations is present throughout the Americas, with continual influence of European males, while Native American females contribute mainly to populations of the Caribbean and South America. The high non-European female contribution to the pool of European-derived populations is consistently characteristic of Iberian colonization. These data suggest that genomic data correlate well with historical records of colonization in the Americas