Rett Syndrome

Rett syndrome is a thief! It robs little girls of their projected life. It lulls their families into a false sense of security while their little girls develop normally for 6 to 18 months. Then it insidiously robs them of their skills and abilities until they are trapped in a body that won't respond. These little girls are called "silent angels" (Hunter, 2007). Rett syndrome (RS) was originally identified in 1966 by the Austrian neurologist Andreas Rett, but his research and findings were written in an obscure form of the German language the medical world could not and did not translate. It wasn't until 1983, that Rett syndrome was re-identified and labeled as its own disorder (Hunter, 2007). The Rett Syndrome Research Foundation (2006) summarizes the condition best with: Rett syndrome is a debilitating neurological disorder diagnosed almost exclusively in females. Children with Rett syndrome appear to develop normally until 6 to 18 months of age when they enter a period of regression, losing speech and motor skills. Most develop repetitive hand movements, irregular breathing patterns, seizures and extreme motor control problems. Rett syndrome leaves its victims profoundly disabled, requiring maximum assistance with every aspect of daily living. There is no cure. (Retrieved October 14, 2008 from http://www.rsrf.org/about_rett_syndrome/) Research is ever going to regards to Rett syndrome. What is known as of now is that Rett syndrome is caused by a mutation of the gene MECP2. It is not passed down in families and it knows no ethnic boundaries. The majority of Rett girls live to adulthood (RSRF, 2006). The male child doesn't usually survive birth with Rett syndrome

Leaders Fostering Resiliency In Schools

This single case study of a school district described how school leaders created educational programs and practices that feature elements of a caring environment wihtin which students were frequently offered choices in their learning experiences. Data from a survey, school observations, interviews and formal documents were analyzed using a mixed method qualitative approach of triangulation, expansion and complementarity methods of analysis. The study determined that a caring environment with student choices existed in the district and its programs and practices were consistent with the literature on resiliency. The study also found the environment that developed through several critical events over eighteen years translated a vision into the organizational mission and belief. The leadership role was characterized by commitment to vision, mobilization of structure, a superintendent's stable tenure, and a proliferation of programs in a small school district size

Pattern and prevalence of vaping nicotine and non-nicotine drugs in the United Kingdom: a cross-sectional study

Objectives: Electronic vaping devices are being used to consume nicotine and non-nicotine psychoactive drugs. We aimed to determine the pattern and prevalence of using vaping devices for nicotine and/or non-nicotine drug administration in the United Kingdom and how these differ by drug type and individual sociodemographic characteristics. We explored reasons for vaping onset and continuation. Design: An online cross-sectional survey Participants: A convenience sample of adults (aged ≥18 years) in the UK. Primary and secondary outcome measures: The primary outcome was prevalence of current use (within the last 30 days) of a vaping device to administer either nicotine or 18 types of non-nicotine drugs. We additionally evaluated reasons for onset and continuation of vaping. Sociodemographic characteristics were compared between the UK general population using census data and those vaping non-nicotine drugs. Results: We recruited 4027 participants of whom 1637 (40.7%) had ever used an electronic vaping device; 1495 (37.1%) had ever vaped nicotine and 593 (14.7%) had ever vaped a non-nicotine drug. Overall, 574 (14.3%) currently vaped nicotine and 74 (1.8%) currently vaped a non-nicotine drug. The most common currently vaped non-nicotine drug was cannabis (n=58, 1.4%). For nicotine, people’s modal reasons to start and continue vaping was to quit smoking tobacco. For almost all other drugs, people’s modal reason to start vaping was curiosity and to continue was enjoyment. Compared with the general population, the population who had ever vaped a non-nicotine drug were significantly younger, had more disabilities and fewer identified as white, female, heterosexual or religious. Conclusions: A non-trivial number of people report current use and ever use of an electronic vaping device for non-nicotine drug administration. As vaping technology advances and drug consumption changes, understanding patterns of use and associated behaviours are likely to be increasingly important to both users and healthcare professionals

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Genomic analyses in Cornelia de Lange Syndrome and related diagnoses: Novel candidate genes, <scp>genotype–phenotype</scp> correlations and common mechanisms

Cornelia de Lange Syndrome (CdLS) is a rare, dominantly inherited multisystem developmental disorder characterized by highly variable manifestations of growth and developmental delays, upper limb involvement, hypertrichosis, cardiac, gastrointestinal, craniofacial, and other systemic features. Pathogenic variants in genes encoding cohesin complex structural subunits and regulatory proteins (NIPBL, SMC1A, SMC3, HDAC8, and RAD21) are the major pathogenic contributors to CdLS. Heterozygous or hemizygous variants in the genes encoding these five proteins have been found to be contributory to CdLS, with variants in NIPBL accounting for the majority (&gt;60%) of cases, and the only gene identified to date that results in the severe or classic form of CdLS when mutated. Pathogenic variants in cohesin genes other than NIPBL tend to result in a less severe phenotype. Causative variants in additional genes, such as ANKRD11, EP300, AFF4, TAF1, and BRD4, can cause a CdLS‐like phenotype. The common role that these genes, and others, play as critical regulators of developmental transcriptional control has led to the conditions they cause being referred to as disorders of transcriptional regulation (or “DTRs”). Here, we report the results of a comprehensive molecular analysis in a cohort of 716 probands with typical and atypical CdLS in order to delineate the genetic contribution of causative variants in cohesin complex genes as well as novel candidate genes, genotype–phenotype correlations, and the utility of genome sequencing in understanding the mutational landscape in this population

Clinical outcomes and response to treatment of patients receiving topical treatments for pyoderma gangrenosum: a prospective cohort study

Background: pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. Objective: to estimate the effectiveness of topical therapies in the treatment of PG. Methods: prospective cohort study of UK secondary care patients with a clinical diagnosis of PG suitable for topical treatment (recruited July 2009 to June 2012). Participants received topical therapy following normal clinical practice (mainly Class I-III topical corticosteroids, tacrolimus 0.03% or 0.1%). Primary outcome: speed of healing at 6 weeks. Secondary outcomes: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality-of-life; treatment failure and recurrence. Results: Sixty-six patients (22 to 85 years) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28/66 (43.8%) of ulcers healed by 6 months. Median time-to-healing was 145 days (95% CI: 96 days, ∞). Initial ulcer size was a significant predictor of time-to-healing (hazard ratio 0.94 (0.88;80 1.00); p = 0.043). Four patients (15%) had a recurrence. Limitations: No randomised comparator Conclusion: Topical therapy is potentially an effective first-line treatment for PG that avoids possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone

Rare germline copy number variants (CNVs) and breast cancer risk.

Funder: CIHRGermline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance