Do children with neurological disabilities use more inpatient resources: an observational study.

BACKGROUND: Advances in healthcare have improved the survival of children with neurological disabilities (ND). Studies in the US have shown that children with ND use a substantial proportion of resources in children's hospitals, however, little research has been conducted in the UK. We aimed to test the hypothesis that children with neurological disabilities use more inpatient resources than children without neurological disabilities, and to quantify any significant differences in resource use. METHODS: A retrospective observational study was conducted, looking at the number of hospital admissions, total inpatient days and the reason for admissions for paediatric inpatients from January 1st to March 31st 2015. Inpatients were assigned into one of three groups: children without ND, children with one ND, and children with more than one ND. RESULTS: The sample population included 942 inpatients (mean age 6y 6mo). Children with at least one ND accounted for 15.3% of the inpatients, 17.7% of total hospital inpatient admission episodes, and 27.8% of the total inpatients days. Neurological disability had a statistically significant effect on total hospital admissions (p < 0.001). Neurological disability also had a statistically significant effect on total inpatient days (p < 0.001). Neurological disability increased the length of inpatient stay across medicine, specialties, and surgery. CONCLUSIONS: Children with ND had more frequent hospital admission episode and longer inpatient stays. We identified a smaller group within this population, with arguably more complex neurological disabilities, children with more than one ND. This group had the highest number of admissions and longest inpatient stays. More frequent hospital admissions and longer inpatient stays may place children with ND at greater risk of the adverse effects of hospitalisations. We recommend further investigations looking at each the effects of the different categories of ND on inpatient resource use, and repeat of this study at a national level and over a longer period of time

A Phase 1 Randomized, Double Blind, Placebo Controlled Rectal Safety and Acceptability Study of Tenofovir 1% Gel (MTN-007)

Objective: Rectal microbicides are needed to reduce the risk of HIV acquisition associated with unprotected receptive anal intercourse. The MTN-007 study was designed to assess the safety (general and mucosal), adherence, and acceptability of a new reduced glycerin formulation of tenofovir 1% gel. Methods: Participants were randomized 1:1:1:1 to receive the reduced glycerin formulation of tenofovir 1% gel, a hydroxyethyl cellulose placebo gel, a 2% nonoxynol-9 gel, or no treatment. Each gel was administered as a single dose followed by 7 daily doses. Mucosal safety evaluation included histology, fecal calprotectin, epithelial sloughing, cytokine expression (mRNA and protein), microarrays, flow cytometry of mucosal T cell phenotype, and rectal microflora. Acceptability and adherence were determined by computer-administered questionnaires and interactive telephone response, respectively. Results: Sixty-five participants (45 men and 20 women) were recruited into the study. There were no significant differences between the numbers of ≥ Grade 2 adverse events across the arms of the study. Likelihood of future product use (acceptability) was 87% (reduced glycerin formulation of tenofovir 1% gel), 93% (hydroxyethyl cellulose placebo gel), and 63% (nonoxynol-9 gel). Fecal calprotectin, rectal microflora, and epithelial sloughing did not differ by treatment arms during the study. Suggestive evidence of differences was seen in histology, mucosal gene expression, protein expression, and T cell phenotype. These changes were mostly confined to comparisons between the nonoxynol-9 gel and other study arms. Conclusions: The reduced glycerin formulation of tenofovir 1% gel was safe and well tolerated rectally and should be advanced to Phase 2 development. Trial Registration: ClinicalTrials.gov NCT01232803

A recurrent mosaic mutation of SMO, encoding the hedgehog signal transducer smoothened, is the major cause of Curry-Jones syndrome

Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single affected individual; in another, biopsy of skin lesions showed features of trichoblastoma. The combination of asymmetric clinical features, patchy skin manifestations, and neoplastic association previously led to the suggestion that this could be a mosaic condition, possibly involving hedgehog (Hh) signaling. Here, we show that CJS is caused by recurrent somatic mosaicism for a nonsynonymous variant in SMO (c.1234C&gt;T [p.Leu412Phe]), encoding smoothened (SMO), a G-protein-coupled receptor that transduces Hh signaling. We identified eight mutation-positive individuals (two of whom had not been reported previously) with highly similar phenotypes and demonstrated varying amounts of the mutant allele in different tissues. We present detailed findings from brain MRI in three mutation-positive individuals. Somatic SMO mutations that result in constitutive activation have been described in several tumors, including medulloblastoma, ameloblastoma, and basal cell carcinoma. Strikingly, the most common of these mutations is the identical nonsynonymous variant encoding p.Leu412Phe. Furthermore, this substitution has been shown to activate SMO in the absence of Hh signaling, providing an explanation for tumor development in CJS. This raises therapeutic possibilities for using recently generated Hh-pathway inhibitors. In summary, our work uncovers the major genetic cause of CJS and illustrates strategies for gene discovery in the context of low-level tissue-specific somatic mosaicism

Mouse nuclear myosin I knock-out shows interchangeability and redundancy of myosin isoforms in the cell nucleus.

Nuclear myosin I (NM1) is a nuclear isoform of the well-known "cytoplasmic" Myosin 1c protein (Myo1c). Located on the 11(th) chromosome in mice, NM1 results from an alternative start of transcription of the Myo1c gene adding an extra 16 amino acids at the N-terminus. Previous studies revealed its roles in RNA Polymerase I and RNA Polymerase II transcription, chromatin remodeling, and chromosomal movements. Its nuclear localization signal is localized in the middle of the molecule and therefore directs both Myosin 1c isoforms to the nucleus. In order to trace specific functions of the NM1 isoform, we generated mice lacking the NM1 start codon without affecting the cytoplasmic Myo1c protein. Mutant mice were analyzed in a comprehensive phenotypic screen in cooperation with the German Mouse Clinic. Strikingly, no obvious phenotype related to previously described functions has been observed. However, we found minor changes in bone mineral density and the number and size of red blood cells in knock-out mice, which are most probably not related to previously described functions of NM1 in the nucleus. In Myo1c/NM1 depleted U2OS cells, the level of Pol I transcription was restored by overexpression of shRNA-resistant mouse Myo1c. Moreover, we found Myo1c interacting with Pol II. The ratio between Myo1c and NM1 proteins were similar in the nucleus and deletion of NM1 did not cause any compensatory overexpression of Myo1c protein. We observed that Myo1c can replace NM1 in its nuclear functions. Amount of both proteins is nearly equal and NM1 knock-out does not cause any compensatory overexpression of Myo1c. We therefore suggest that both isoforms can substitute each other in nuclear processes

Purification and functional characterisation of rhiminopeptidase A, a novel aminopeptidase from the venom of Bitis gabonica rhinoceros

This study describes the discovery and characterisation of a novel aminopeptidase A from the venom of B. g. rhinoceros and highlights its potential biological importance. Similar to mammalian aminopeptidases, rhiminopeptidase A might be capable of playing roles in altering the blood pressure and brain function of victims. Furthermore, it could have additional effects on the biological functions of other host proteins by cleaving their N-terminal amino acids. This study points towards the importance of complete analysis of individual components of snake venom in order to develop effective therapies for snake bites

Electronic search strategies to identify reports of cluster randomized trials in MEDLINE: low precision will improve with adherence to reporting standards

BACKGROUND: Cluster randomized trials (CRTs) present unique methodological and ethical challenges. Researchers conducting systematic reviews of CRTs (e.g., addressing methodological or ethical issues) require efficient electronic search strategies (filters or hedges) to identify trials in electronic databases such as MEDLINE. According to the CONSORT statement extension to CRTs, the clustered design should be clearly identified in titles or abstracts; however, variability in terminology may make electronic identification challenging. Our objectives were to (a) evaluate sensitivity ( recall ) and precision of a well-known electronic search strategy ( randomized controlled trial as publication type) with respect to identifying CRTs, (b) evaluate the feasibility of new search strategies targeted specifically at CRTs, and (c) determine whether CRTs are appropriately identified in titles or abstracts of reports and whether there has been improvement over time. METHODS: We manually examined a wide range of health journals to identify a gold standard set of CRTs. Search strategies were evaluated against the gold standard set, as well as an independent set of CRTs included in previous systematic reviews. RESULTS: The existing strategy (randomized controlled trial.pt) is sensitive (93.8%) for identifying CRTs, but has relatively low precision (9%, number needed to read 11); the number needed to read can be halved to 5 (precision 18.4%) by combining with cluster design-related terms using the Boolean operator AND; combining with the Boolean operator OR maximizes sensitivity (99.4%) but would require 28.6 citations read to identify one CRT. Only about 50% of CRTs are clearly identified as cluster randomized in titles or abstracts; approximately 25% can be identified based on the reported units of randomization but are not amenable to electronic searching; the remaining 25% cannot be identified except through manual inspection of the full-text article. The proportion of trials clearly identified has increased from 28% between the years 2000-2003, to 60% between 2004-2007 (absolute increase 32%, 95% CI 17 to 47%). CONCLUSIONS: CRTs should include the phrase cluster randomized trial in titles or abstracts; this will facilitate more accurate indexing of the publication type by reviewers at the National Library of Medicine, and efficient textword retrieval of the subset employing cluster randomization

Toward optimal implementation of cancer prevention and control programs in public health: A study protocol on mis-implementation

Abstract Background Much of the cancer burden in the USA is preventable, through application of existing knowledge. State-level funders and public health practitioners are in ideal positions to affect programs and policies related to cancer control. Mis-implementation refers to ending effective programs and policies prematurely or continuing ineffective ones. Greater attention to mis-implementation should lead to use of effective interventions and more efficient expenditure of resources, which in the long term, will lead to more positive cancer outcomes. Methods This is a three-phase study that takes a comprehensive approach, leading to the elucidation of tactics for addressing mis-implementation. Phase 1: We assess the extent to which mis-implementation is occurring among state cancer control programs in public health. This initial phase will involve a survey of 800 practitioners representing all states. The programs represented will span the full continuum of cancer control, from primary prevention to survivorship. Phase 2: Using data from phase 1 to identify organizations in which mis-implementation is particularly high or low, the team will conduct eight comparative case studies to get a richer understanding of mis-implementation and to understand contextual differences. These case studies will highlight lessons learned about mis-implementation and identify hypothesized drivers. Phase 3: Agent-based modeling will be used to identify dynamic interactions between individual capacity, organizational capacity, use of evidence, funding, and external factors driving mis-implementation. The team will then translate and disseminate findings from phases 1 to 3 to practitioners and practice-related stakeholders to support the reduction of mis-implementation. Discussion This study is innovative and significant because it will (1) be the first to refine and further develop reliable and valid measures of mis-implementation of public health programs; (2) bring together a strong, transdisciplinary team with significant expertise in practice-based research; (3) use agent-based modeling to address cancer control implementation; and (4) use a participatory, evidence-based, stakeholder-driven approach that will identify key leverage points for addressing mis-implementation among state public health programs. This research is expected to provide replicable computational simulation models that can identify leverage points and public health system dynamics to reduce mis-implementation in cancer control and may be of interest to other health areas

Quorum Sensing Primes the Oxidative Stress Response in the Insect Endosymbiont, Sodalis glossinidius

quorum sensing system relies on the function of two regulatory proteins; SogI (a LuxI homolog) synthesizes a signaling molecule, characterized as N-(3-oxohexanoyl) homoserine lactone (OHHL), and SogR1 (a LuxR homolog) interacts with OHHL to modulate transcription of specific target genes. and SOPE. and SOPE indicates the potential for neofunctionalization to occur during the process of genome degeneration

Development and assessment of a questionnaire for a descriptive cross – sectional study concerning parents' knowledge, attitudes and practises in antibiotic use in Greece

<p>Abstract</p> <p>Background</p> <p>Upper Respiratory Infections (URIs) are common in children. The cause is usually viral, but parents' attitude often contributes to inappropriate antibiotic prescribing, promoting antibiotic resistance. The objective is to describe the process of developing a questionnaire to assess parents' Knowledge, Attitude and Practices (KAP) concerning the role of antibiotics when children suffer from URIs, as well as to evaluate the response rates, the completeness and the reliability (Cronbach) of the questionnaires. Finally, to note any limitations of the study.</p> <p>Methods</p> <p>Literature review, along with pre – testing yielded a questionnaire designed to assess the parents' KAP – level. A postal survey was set, in a national sample of 200 schools stratified by geographical region. The participants consist of a multistage geographical cluster sample of 8000 parents. The influence of demographic characteristics (i.e. sex, age, education) was analyzed. Cronbach index test and factor analysis were used to assess the reliability of the questionnaire.</p> <p>Results</p> <p>The response rate of the parents was 69%. Islands presented the lowest response rate while in Northern Greece the response rate was the highest. Sixty – eight point nine percent of the sample returned questionnaires fully completed, while 91.5% completed 95% of the questions. Three questions out of 70 were answered in a very low rate which was associated mostly with immigrant respondents. The section describing parents' attitude toward antibiotic use was not completed as much as the sections of knowledge or practices. The questions were factor analyzed and 10 out of the 21 extracted factors were finally evaluated, reducing the number of independent variables to 46. The reliability of the questionnaire was 0.55. However, only items that increased the Cronbach when added were eventually included in the final scales raising the internal consistency to 0.68. Limitations of the study, such as the vocabulary and form of the questionnaire and the idiocycrancy of the respondents, emerged during the analysis.</p> <p>Conclusion</p> <p>The response rate and the completeness of the questionnaires were higher than expected, probably attributed to the involvement of the teachers. The study findings were satisfactory regarding the development of a reliable instrument capable to measure parents' KAP characteristics.</p