Stroke in children with posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities (PHACE) syndrome: a systematic review of the literature.

Background and purposePHACE is an acronym for posterior fossa brain malformations, hemangiomas, arterial anomalies, coarctation of the aorta and cardiac defects, and eye abnormalities. Several case reports of arterial ischemic stroke (AIS) in individuals with PHACE have been published, but risk factors for AIS in PHACE have not been clearly defined. The objective of this article is to review all cases of stroke in PHACE in children and describe clinical characteristics that may be associated with an increased risk of AIS.MethodsA literature and registry search was conducted to identify patients with PHACE who had experienced AIS. Data were analyzed to determine age of onset, presenting signs and symptoms, and clinical features among this cohort compared with PHACE without AIS.ResultsTwenty-two individuals with PHACE and AIS were identified. Imaging of the arteries of the head and neck was reported in 20 of 22. Narrowing or nonvisualization of at least 1 great cerebral vessel was present in 19 of 20 and of those, 15 had ≥ 2 vessels involved. Aortic arch anomalies were reported in 13 of 22 individuals.ConclusionsAplasia, hypoplasia, or occlusion of a major cerebral artery appears to be a significant risk factor for AIS in children with PHACE, especially when >1 vessel is involved or if there is coarctation of the aorta

The SHED-IT community trial study protocol: a randomised controlled trial of weight loss programs for overweight and obese men

<p>Abstract</p> <p>Background</p> <p>Obesity is a major cause of preventable death in Australia with prevalence increasing at an alarming rate. Of particular concern is that approximately 68% of men are overweight/obese, yet are notoriously difficult to engage in weight loss programs, despite being more susceptible than women to adverse weight-related outcomes. There is a need to develop and evaluate obesity treatment programs that target and appeal to men. The primary aim of this study is to evaluate the efficacy of two relatively low intensity weight loss programs developed specifically for men.</p> <p>Methods and Design</p> <p>The study design is an assessor blinded, parallel-group randomised controlled trial that recruited 159 overweight and obese men in Newcastle, Australia. Inclusion criteria included: BMI 25-40 (kg/m²); no participation in other weight loss programs during the study; pass a health-screening questionnaire and pre-exercise risk assessment; available for assessment sessions; access to a computer with e-mail and Internet facilities; and own a mobile phone. Men were recruited to the SHED-IT (Self-Help, Exercise and Diet using Internet Technology) study via the media and emails sent to male dominated workplaces. Men were stratified by BMI category (overweight, obese class I, obese class II) and randomised to one of three groups: (1) SHED-IT <it>Resources </it>- provision of materials (DVD, handbooks, pedometer, tape measure) with embedded behaviour change strategies to support weight loss; (2) SHED-IT <it>Online </it>- same materials as SHED-IT <it>Resources </it>plus access to and instruction on how to use the study website; (3) Wait-list Control. The intervention programs are three months long with outcome measures taken by assessors blinded to group allocation at baseline, and 3- and 6-months post baseline. Outcome measures include: weight (primary outcome), % body fat, waist circumference, blood pressure, resting heart rate, objectively measured physical activity, self-reported dietary intake, sedentary behaviour, physical activity and dietary cognitions, sleepiness, quality of life, and perceived sexual health. Generalised linear mixed models will be used to assess all outcomes for the impact of group (<it>Resources</it>, <it>Online</it>, and <it>Control</it>), time (treated as categorical with levels baseline, 3-months and 6-months) and the group-by-time interaction. These three terms will form the base model. 'Intention-to-treat' analysis will include all randomised participants.</p> <p>Discussion</p> <p>Our study will compare evidence-based and theoretically driven, low cost and easily disseminated strategies specifically targeting weight loss in men. The SHED-IT community trial will provide evidence to inform development and dissemination of sustainable strategies to reduce obesity in men.</p> <p>Trial Registration</p> <p>Australian New Zealand Clinical Trials Registry (ACTRN12610000699066)</p

Spermatogenesis-Specific Features of the Meiotic Program in Caenorhabditis elegans

In most sexually reproducing organisms, the fundamental process of meiosis is implemented concurrently with two differentiation programs that occur at different rates and generate distinct cell types, sperm and oocytes. However, little is known about how the meiotic program is influenced by such contrasting developmental programs. Here we present a detailed timeline of late meiotic prophase during spermatogenesis in Caenorhabditis elegans using cytological and molecular landmarks to interrelate changes in chromosome dynamics with germ cell cellularization, spindle formation, and cell cycle transitions. This analysis expands our understanding C. elegans spermatogenesis, as it identifies multiple spermatogenesis-specific features of the meiotic program and provides a framework for comparative studies. Post-pachytene chromatin of spermatocytes is distinct from that of oocytes in both composition and morphology. Strikingly, C. elegans spermatogenesis includes a previously undescribed karyosome stage, a common but poorly understood feature of meiosis in many organisms. We find that karyosome formation, in which chromosomes form a constricted mass within an intact nuclear envelope, follows desynapsis, involves a global down-regulation of transcription, and may support the sequential activation of multiple kinases that prepare spermatocytes for meiotic divisions. In spermatocytes, the presence of centrioles alters both the relative timing of meiotic spindle assembly and its ultimate structure. These microtubule differences are accompanied by differences in kinetochores, which connect microtubules to chromosomes. The sperm-specific features of meiosis revealed here illuminate how the underlying molecular machinery required for meiosis is differentially regulated in each sex

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Introducing Physician Assistants to Ontario

In 2006, the Ontario Ministry of Health and Long-Term Care (MOHLTC) introduced Physician Assistants (PAs) through the announcement of demonstration projects, education and training programs, and subsequent funding. PAs are directly supervised by physicians and act as physician extenders by performing acts as delegated to them by their supervising physicians. PAs were proposed as a potential solution to help improve access to health care and reduce wait times throughout the province. Prior to the 2006 Ministry announcement, there was little public discussion regarding the acceptance of the PA role or its sustainability. Opposition from nursing and other groups emerged in response to the 2006 announcement and flared again when stakeholder comments were solicited in 2012 as part of the PA application for status as regulated health professionals. As a health reform, the introduction of PAs has neither succeeded nor failed. In 2013, the majority of PA funding continues to be provided by the MOHLTC, and it is unknown whether the PA role will be sustainable when the MOHTLC withdraws salary funding and health system employers must decide whether or not to continue employing PAs at their own expense. Le ministère de la santé et des soins de longue durée de l’Ontario (MSSLD) a introduit les Adjoints au Médecin (AM) en 2006 en annonçant des projets expérimentaux, des programmes de formation et d’éducation, ainsi que des financements à venir. Les AMs sont placés sous la direction directe des médecins et agissent comme des prolongements des médecins en effectuant des actes qui leur sont délégués par leur médecin superviseur. Les AMs ont été vus comme une solution possible aux problèmes d’accès aux soins et de délais d’attente dans la province. L’acceptabilité et la pérennité du rôle des AMs n’avaient pas vraiment été discutées publiquement avant cette annonce du ministère en 2006. Les infirmières, ainsi que d’autres groupes, ont marqué leur opposition en réponse à l’annonce de 2006, et de nouveau en 2012 lorsque des commentaires des parties prenantes ont été sollicitées dans le cadre d’un dépôt de demande de régulation en profession médicale par les AMs. L’introduction des AMs ne peut être qualifiée de succès ou d’échec. La majeure partie du financement des AMs est toujours assurée par le MSSLD en 2013 et il est impossible de savoir si le rôle des AMs sera pérennisé lorsque le MSSLD arrêtera de financer leur salaires, laissant les employeurs au sein du système de santé décider par eux mêmes s’ils veulent ou non continuer à employer des AMs sur leur propre budget.

Genetic Variation, Not Cell Type of Origin, Underlies the Majority of Identifiable Regulatory Differences in iPSCs

The advent of induced pluripotent stem cells (iPSCs) revolutionized human genetics by allowing us to generate pluripotent cells from easily accessible somatic tissues. This technology can have immense implications for regenerative medicine, but iPSCs also represent a paradigm shift in the study of complex human phenotypes, including gene regulation and disease. Yet, an unresolved caveat of the iPSC model system is the extent to which reprogrammed iPSCs retain residual phenotypes from their precursor somatic cells. To directly address this issue, we used an effective study design to compare regulatory phenotypes between iPSCs derived from two types of commonly used somatic precursor cells. We find a remarkably small number of differences in DNA methylation and gene expression levels between iPSCs derived from different somatic precursors. Instead, we demonstrate genetic variation is associated with the majority of identifiable variation in DNA methylation and gene expression levels. We show that the cell type of origin only minimally affects gene expression levels and DNA methylation in iPSCs, and that genetic variation is the main driver of regulatory differences between iPSCs of different donors. Our findings suggest that studies using iPSCs should focus on additional individuals rather than clones from the same individual

Expression Quantitative Trait Locus Mapping Studies in Mid-secretory Phase Endometrial Cells Identifies <i>HLA-F</i> and <i>TAP2</i> as Fecundability-Associated Genes

Fertility traits in humans are heritable, however, little is known about the genes that influence reproductive outcomes or the genetic variants that contribute to differences in these traits between individuals, particularly women. To address this gap in knowledge, we performed an unbiased genome-wide expression quantitative trait locus (eQTL) mapping study to identify common regulatory (expression) single nucleotide polymorphisms (eSNPs) in mid-secretory endometrium. We identified 423 cis-eQTLs for 132 genes that were significant at a false discovery rate (FDR) of 1%. After pruning for strong LD (r2 >0.95), we tested for associations between eSNPs and fecundability (the ability to get pregnant), measured as the length of the interval to pregnancy, in 117 women. Two eSNPs were associated with fecundability at a FDR of 5%; both were in the HLA region and were eQTLs for the TAP2 gene (P = 1.3x10-4) and the HLA-F gene (P = 4.0x10-4), respectively. The effects of these SNPs on fecundability were replicated in an independent sample. The two eSNPs reside within or near regulatory elements in decidualized human endometrial stromal cells. Our study integrating eQTL mapping in a primary tissue with association studies of a related phenotype revealed novel genes and associated alleles with independent effects on fecundability, and identified a central role for two HLA region genes in human implantation success

The SHED-IT community trial: a randomised controlled trial of Internet- and paper-based weight loss programs tailored for overweight and obese men

There is limited evidence for effective obesity treatment programs that engage men. This study evaluated the efficacy of two gender-tailored weight loss interventions for men, which required no face-to-face contact. This was a three-arm, randomized controlled trial: (1) Resources (n=54), gender-tailored weight loss materials (DVD, handbooks, pedometer, tape measure); (2) Online (n=53), Resources materials plus study website and e-feedback; and (3) Wait-list control (n=52). The interventions lasted 3 months and were grounded in Social Cognitive Theory. At 6 months, significantly greater weight loss was observed for the Online (−4.7 kg; 95 % CI −6.1, −3.2) and Resources (−3.7 kg; 95 % CI −4.9, −2.5) groups compared to the control (−0.5 kg; 95 % CI −1.4, 0.4). Additionally, both intervention groups significantly improved body mass index, percent body fat, waist circumference, blood pressure, physical activity, quality of life, alcohol risk, and portion size, compared to controls. Men achieved significant weight loss after receiving novel, minimal-contact, gender-tailored programs, which were designed for widespread dissemination