Sibling relationships and family functioning in siblings of early adolescents, adolescents and young adults with autism spectrum disorder

The purpose of the study was to investigate how family functioning (defined as the ability that family members hold to manage stressful events, and intimate and social relationships), the degree to which family members feel happy and fulfilled with each other (called family satisfaction), and the demographical characteristics of siblings (age and gender) impacted on sibling relationships. The Circumplex Model of Marital and Family Systems and Behavioral Systems constituted the theoretical frameworks that guided our study. Eighty-six typically developing adolescents and young adults having a sister or a brother with autism spectrum disorder were enrolled. Results indicated that the youngest age group (early adolescents) reported to engage more frequently in negative behaviors with their siblings with ASD than the two older age groups (middle adolescents and young adults). No significant differences were found among the three age groups regarding behaviors derived from attachment, caregiving and affiliative systems. Family satisfaction and age significantly predicted behaviors during sibling interactions. Suggestions on prevention and intervention programs were discussed in order to prevent parentification among typically developing siblings and decrease episodes of quarrels and overt conflicts between brothers and sisters with and without AS

Managing lifestyle change to reduce coronary risk: a synthesis of qualitative research on peoples’ experiences

Background Coronary heart disease is an incurable condition. The only approach known to slow its progression is healthy lifestyle change and concordance with cardio-protective medicines. Few people fully succeed in these daily activities so potential health improvements are not fully realised. Little is known about peoples’ experiences of managing lifestyle change. The aim of this study was to synthesise qualitative research to explain how participants make lifestyle change after a cardiac event and explore this within the wider illness experience. Methods A qualitative synthesis was conducted drawing upon the principles of meta-ethnography. Qualitative studies were identified through a systematic search of 7 databases using explicit criteria. Key concepts were identified and translated across studies. Findings were discussed and diagrammed during a series of audiotaped meetings. Results The final synthesis is grounded in findings from 27 studies, with over 500 participants (56% male) across 8 countries. All participants experienced a change in their self-identity from what was ‘familiar’ to ‘unfamiliar’. The transition process involved ‘finding new limits and a life worth living’ , ‘finding support for self’ and ‘finding a new normal’. Analyses of these concepts led to the generation of a third order construct, namely an ongoing process of ‘reassessing past, present and future lives’ as participants considered their changed identity. Participants experienced a strong urge to get back to ‘normal’. Support from family and friends could enable or constrain life change and lifestyle changes. Lifestyle change was but one small part of a wider ‘life’ change that occurred. Conclusions The final synthesis presents an interpretation, not evident in the primary studies, of a person-centred model to explain how lifestyle change is situated within ‘wider’ life changes. The magnitude of individual responses to a changed health status varied. Participants experienced distress as their notion of self identity shifted and emotions that reflected the various stages of the grief process were evident in participants’ accounts. The process of self-managing lifestyle took place through experiential learning; the level of engagement with lifestyle change reflected an individual’s unique view of the balance needed to manage ‘realistic change’ whilst leading to a life that was perceived as ‘worth living’. Findings highlight the importance of providing person centred care that aligns with both psychological and physical dimensions of recovery which are inextricably linked

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Discovery and characterization of chromatin states for systematic annotation of the human genome

A plethora of epigenetic modifications have been described in the human genome and shown to play diverse roles in gene regulation, cellular differentiation and the onset of disease. Although individual modifications have been linked to the activity levels of various genetic functional elements, their combinatorial patterns are still unresolved and their potential for systematic de novo genome annotation remains untapped. Here, we use a multivariate Hidden Markov Model to reveal 'chromatin states' in human T cells, based on recurrent and spatially coherent combinations of chromatin marks. We define 51 distinct chromatin states, including promoter-associated, transcription-associated, active intergenic, large-scale repressed and repeat-associated states. Each chromatin state shows specific enrichments in functional annotations, sequence motifs and specific experimentally observed characteristics, suggesting distinct biological roles. This approach provides a complementary functional annotation of the human genome that reveals the genome-wide locations of diverse classes of epigenetic function.National Science Foundation (U.S.). (Award 0905968)National Human Genome Research Institute (U.S.) (Award U54-HG004570)National Human Genome Research Institute (U.S.) (Award RC1-HG005334

Deletion of Nlrp3 protects from inflammation-induced skeletal muscle atrophy

BACKGROUND: Critically ill patients develop atrophic muscle failure, which increases morbidity and mortality. Interleukin-1β (IL-1β) is activated early in sepsis. Whether IL-1β acts directly on muscle cells and whether its inhibition prevents atrophy is unknown. We aimed to investigate if IL-1β activation via the Nlrp3 inflammasome is involved in inflammation-induced atrophy. METHODS: We performed an experimental study and prospective animal trial. The effect of IL-1β on differentiated C2C12 muscle cells was investigated by analyzing gene-and-protein expression, and atrophy response. Polymicrobial sepsis was induced by cecum ligation and puncture surgery in Nlrp3 knockout and wild type mice. Skeletal muscle morphology, gene and protein expression, and atrophy markers were used to analyze the atrophy response. Immunostaining and reporter-gene assays showed that IL-1β signaling is contained and active in myocytes. RESULTS: Immunostaining and reporter gene assays showed that IL-1β signaling is contained and active in myocytes. IL-1β increased Il6 and atrogene gene expression resulting in myocyte atrophy. Nlrp3 knockout mice showed reduced IL-1β serum levels in sepsis. As determined by muscle morphology, organ weights, gene expression, and protein content, muscle atrophy was attenuated in septic Nlrp3 knockout mice, compared to septic wild-type mice 96 h after surgery. CONCLUSIONS: IL-1β directly acts on myocytes to cause atrophy in sepsis. Inhibition of IL-1β activation by targeting Nlrp3 could be useful to prevent inflammation-induced muscle failure in critically ill patients

Socioeconomic status, severity of disease and level of family members’ care in adult surgical intensive care patients: the prospective ECSSTASI study

Low socioeconomic status (SES) is associated with increased mortality from cardiovascular disease, cancer and trauma. However, individual-level prospective data on SES in relation to health outcomes among critically ill patients admitted to intensive care units (ICU) are unavailable. In a cohort of 1,006 patients at a 24-bed surgical ICU of an academic tertiary care facility in Germany, we examined levels of SES in relation to disease severity at admission, time period of mechanical ventilation, length of stay and frequency of phone calls and visits by next-of-kin. Patients with low SES had higher risk for Sequential Organ Failure Assessment (SOFA) score greater or equal to 5 [multivariate-adjusted odds ratio (OR) 1.49; 95% confidence interval (CI) 0.95-2.33; p = 0.029] and a trend for higher risk for Simplified Acute Physiology Score (SAPS II) greater or equal to 31 (OR 1.28; 95% CI 0.80-2.05; p = 0.086) at admission as compared with patients with high SES. When compared with men with high SES, those with low SES had greater risk for ICU treatment a parts per thousand yen5 days (multivariate-adjusted OR 1.99; 95% CI 1.06-3.74; p = 0.036) and showed a trend for a low number of visits from next-of-kin (< 0.5 visits per day) (OR 1.85; 95% CI 0.79-4.30; p = 0.054). In women such associations could not be demonstrated. Socioeconomic status is inversely related to severity of disease at admission and to length of stay in ICU, and positively associated with the level of care by next-of-kin. Whether relations differ by gender requires further examination

Codon usage in vertebrates is associated with a low risk of acquiring nonsense mutations

<p>Abstract</p> <p>Background</p> <p>Codon usage in genomes is biased towards specific subsets of codons. Codon usage bias affects translational speed and accuracy, and it is associated with the tRNA levels and the GC content of the genome. Spontaneous mutations drive genomes to a low GC content. Active cellular processes are needed to maintain a high GC content, which influences the codon usage of a species. Loss-of-function mutations, such as nonsense mutations, are the molecular basis of many recessive alleles, which can greatly affect the genome of an organism and are the cause of many genetic diseases in humans.</p> <p>Methods</p> <p>We developed an event based model to calculate the risk of acquiring nonsense mutations in coding sequences. Complete coding sequences and genomes of 40 eukaryotes were analyzed for GC and CpG content, codon usage, and the associated risk of acquiring nonsense mutations. We included one species per genus for all eukaryotes with available reference sequence.</p> <p>Results</p> <p>We discovered that the codon usage bias detected in genomes of high GC content decreases the risk of acquiring nonsense mutations (Pearson's <it>r </it>= -0.95; <it>P </it>< 0.0001). In the genomes of all examined vertebrates, including humans, this risk was lower than expected (0.93 ± 0.02; mean ± SD) and lower than the risk in genomes of non-vertebrates (1.02 ± 0.13; <it>P </it>= 0.019).</p> <p>Conclusions</p> <p>While the maintenance of a high GC content is energetically costly, it is associated with a codon usage bias harboring a low risk of acquiring nonsense mutations. The reduced exposure to this risk may contribute to the fitness of vertebrates.</p

Awareness and acceptability of human papillomavirus vaccine: an application of the instrumental variables bivariate probit model

<p>Abstract</p> <p>Background</p> <p>Although lower uptake rates of the human papillomavirus (HPV) vaccine among socioeconomically disadvantaged populations have been documented, less is known about the relationships between awareness and acceptability, and other factors affecting HPV vaccine uptake.</p> <p>The current study aimed to estimate the potential effectiveness of increased HPV vaccine awareness on the acceptability of HPV vaccination in a nationally representative sample of women, using a methodology that controlled for potential non-random selection.</p> <p>Methods</p> <p>This study used a population-based sample from the 2007 Health Information National Trends Survey, a cross-sectional study of the US population aged 18 years or older, and focused on the subsample of 742 women who have any female children under the age of 18 years in the household. An instrumental variables bivariate probit model was used to jointly estimate HPV vaccine awareness and acceptability.</p> <p>Results</p> <p>The proportion of HPV vaccine acceptability among the previously aware and non-aware groups was 58% and 47%, respectively. Results from the instrumental variables bivariate probit model showed that the estimated marginal effect of awareness on acceptability was 46 percentage points, an effect that was even greater than observed.</p> <p>Conclusions</p> <p>Among populations who are not currently aware of the HPV vaccine, the potential impact of raising awareness on acceptability of HPV vaccination is substantial. This finding provides additional support to strengthening public health programs that increase awareness and policy efforts that address barriers to HPV vaccination.</p

Diabetes-related molecular signatures in infrared spectra of human saliva

WOS: 000290261500001PubMed ID: 20630088Background: There is an ongoing need for improvements in non-invasive, point-of-care tools for the diagnosis and prognosis of diabetes mellitus. Ideally, such technologies would allow for community screening. Methods: In this study, we employed infrared spectroscopy as a novel diagnostic tool in the prediction of diabetic status by analyzing the molecular and sub-molecular spectral signatures of saliva collected from subjects with diabetes (n = 39) and healthy controls (n = 22). Results: Spectral analysis revealed differences in several major metabolic components - lipid, proteins, glucose, thiocyanate and carboxylate - that clearly demarcate healthy and diseased saliva. The overall accuracy for the diagnosis of diabetes based on infrared spectroscopy was 100% on the training set and 88.2% on the validation set. Therefore, we have established that infrared spectroscopy can be used to generate complex biochemical profiles in saliva and identify several potential diabetes-associated spectral features. Conclusions: Infrared spectroscopy may represent an appropriate tool with which to identify novel diseases mechanisms, risk factors for diabetic complications and markers of therapeutic efficacy. Further study into the potential utility of infrared spectroscopy as diagnostic and prognostic tool for diabetes is warranted