Death from colonic disease in epidermolysis bullosa dystrophica

BACKGROUND: Squamous cell carcinomas and renal failure were reported the causes of death in patients with recessive dystrophic epidermolysis bullosa (RDEB). Death from colonic disease in epidermolysis bullosa (EB) is never reported. CASE PRESENTATION: We demonstrate a male patient with RDEB. He suffered megacolon due to fecal impaction and died from sigmoid colon perforation with peritonitis at age 35 years. CONCLUSION: Constipation is a common clinical feature of RDEB, but fetal complications of chronic constipation are rarely reported. To the author's best knowledge, it has not been reported or recognized in the English literature previously. The aggressive assessment of constipation with fecal impaction is recommended in patients with RDEB

Relationship of cognitive function in patients with schizophrenia in remission to disability: a cross-sectional study in an Indian sample

Background: Cognitive deficits in various domains have been consistently replicated in patients with schizophrenia. Most studies looking at the relationship between cognitive dysfunction and functional disability are from developed countries. Studies from developing countries are few. The purpose of the present study was to compare the neurocognitive function in patients with schizophrenia who were in remission with that of normal controls and to determine if there is a relationship between measures of cognition and functional disability. <p/>Methods: This study was conducted in the Psychiatric Unit of a General Hospital in Mumbai, India. Cognitive function in 25 patients with schizophrenia in remission was compared to 25 normal controls. Remission was confirmed using the brief psychiatric rating scale (BPRS) and scale for the assessment of negative symptoms (SANS). Subjects were administered a battery of cognitive tests covering aspects of memory, executive function and attention. The results obtained were compared between the groups. Correlation analysis was used to look for relationship between illness factors, cognitive function and disability measured using the Indian disability evaluation and assessment scale. <p/>Results: Patients with schizophrenia showed significant deficits on tests of attention, concentration, verbal and visual memory and tests of frontal lobe/executive function. They fared worse on almost all the tests administered compared to normal controls. No relationship was found between age, duration of illness, number of years of education and cognitive function. In addition, we did not find a statistically significant relationship between cognitive function and scores on the disability scale. <p/>Conclusion: The data suggests that persistent cognitive deficits are seen in patients with schizophrenia under remission. The cognitive deficits were not associated with symptomatology and functional disability. It is possible that various factors such as employment and family support reduce disability due to schizophrenia in developing countries like India. Further studies from developing countries are required to explore the relationship between cognitive deficits, functional outcome and the role of socio-cultural variables as protective factors

From theory to 'measurement' in complex interventions: methodological lessons from the development of an e-health normalisation instrument

<b>Background</b> Although empirical and theoretical understanding of processes of implementation in health care is advancing, translation of theory into structured measures that capture the complex interplay between interventions, individuals and context remain limited. This paper aimed to (1) describe the process and outcome of a project to develop a theory-based instrument for measuring implementation processes relating to e-health interventions; and (2) identify key issues and methodological challenges for advancing work in this field.<p></p> <b>Methods</b> A 30-item instrument (Technology Adoption Readiness Scale (TARS)) for measuring normalisation processes in the context of e-health service interventions was developed on the basis on Normalization Process Theory (NPT). NPT focuses on how new practices become routinely embedded within social contexts. The instrument was pre-tested in two health care settings in which e-health (electronic facilitation of healthcare decision-making and practice) was used by health care professionals.<p></p> <b>Results</b> The developed instrument was pre-tested in two professional samples (N = 46; N = 231). Ratings of items representing normalisation 'processes' were significantly related to staff members' perceptions of whether or not e-health had become 'routine'. Key methodological challenges are discussed in relation to: translating multi-component theoretical constructs into simple questions; developing and choosing appropriate outcome measures; conducting multiple-stakeholder assessments; instrument and question framing; and more general issues for instrument development in practice contexts.<p></p> <b>Conclusions</b> To develop theory-derived measures of implementation process for progressing research in this field, four key recommendations are made relating to (1) greater attention to underlying theoretical assumptions and extent of translation work required; (2) the need for appropriate but flexible approaches to outcomes measurement; (3) representation of multiple perspectives and collaborative nature of work; and (4) emphasis on generic measurement approaches that can be flexibly tailored to particular contexts of study

The molecular function of kallikrein-related peptidase 14 demonstrates a key modulatory role in advanced prostate cancer

Kallikrein-related peptidase 14 (KLK14) is one of several secreted KLK serine proteases involved in prostate cancer (PCa) pathogenesis. While relatively understudied, recent reports have identified KLK14 as overexpressed during PCa development. However, the modulation of KLK14 expression during PCa progression and the molecular and biological functions of this protease in the prostate tumour microenvironment remain unknown. To determine the modulation of KLK14 expression during PCa progression, we analysed the expression levels of KLK14 in patient samples using publicly available databases and immunohistochemistry. In order to delineate the molecular mechanisms involving KLK14 in PCa progression, we integrated proteomic, transcriptomic and in vitro assays with the goal to identify substrates, related-signalling pathways and functional roles of this protease. We showed that KLK14 expression is elevated in advanced PCa, and particularly in metastasis. Additionally, KLK14 levels were found to be decreased in PCa tissues from patients responsive to neo-adjuvant therapy compared to untreated patients. Furthermore, we also identified that KLK14 expression re-occurred in patients who developed castrate-resistant PCa. The combination of proteomic and transcriptomic analysis as well as functional assays revealed several new KLK14-substrates (agrin, desmoglein 2, vitronectin, laminins) and KLK14-regulated genes (Interleukin 32, midkine, Sox9), particularly an involvement of the MAPK1 and IL1RN pathways, and an involvement of KLK14 in the regulation of cellular migration, supporting its involvement in aggressive features of PCa progression. In conclusion, our work showed that KLK14 expression is associated with the development of aggressive PCa suggesting that targeting this protease could offer a novel route to limit the progression of prostate tumours. Additional work is necessary to determine the benefits and implications of targeting/co-targeting KLK14 in PCa as well as to determine the potential use of KLK14 expression as a predictor of PCa aggressiveness or response to treatment

The Universal One-Loop Effective Action

We present the universal one-loop effective action for all operators of dimension up to six obtained by integrating out massive, non-degenerate multiplets. Our general expression may be applied to loops of heavy fermions or bosons, and has been checked against partial results available in the literature. The broad applicability of this approach simplifies one-loop matching from an ultraviolet model to a lower-energy effective field theory (EFT), a procedure which is now reduced to the evaluation of a combination of matrices in our universal expression, without any loop integrals to evaluate. We illustrate the relationship of our results to the Standard Model (SM) EFT, using as an example the supersymmetric stop and sbottom squark Lagrangian and extracting from our universal expression the Wilson coefficients of dimension-six operators composed of SM fields.Comment: 30 pages, v2 contains additional comments and corrects typos, version accepted for publication in JHE

Role of Esrrg in the Fibrate-Mediated Regulation of Lipid Metabolism Genes in Human ApoA-I Transgenic Mice

We have used a new ApoA-I transgenic mouse model to identify by global gene expression profiling, candidate genes that affect lipid and lipoprotein metabolism in response to fenofibrate treatment. Multilevel bioinformatical analysis and stringent selection criteria (2-fold change, 0% false discovery rate) identified 267 significantly changed genes involved in several molecular pathways. The fenofibrate-treated group did not have significantly altered levels of hepatic human APOA-I mRNA and plasma ApoA-I compared with the control group. However, the treatment increased cholesterol levels to 1.95-fold mainly due to the increase in high-density lipoprotein (HDL) cholesterol. The observed changes in HDL are associated with the upregulation of genes involved in phospholipid biosynthesis and lipid hydrolysis, as well as phospholipid transfer protein. Significant upregulation was observed in genes involved in fatty acid transport and β-oxidation, but not in those of fatty acid and cholesterol biosynthesis, Krebs cycle and gluconeogenesis. Fenofibrate changed significantly the expression of seven transcription factors. The estrogen receptor-related gamma gene was upregulated 2.36-fold and had a significant positive correlation with genes of lipid and lipoprotein metabolism and mitochondrial functions, indicating an important role of this orphan receptor in mediating the fenofibrate-induced activation of a specific subset of its target genes.National Institutes of Health (HL48739 and HL68216); European Union (LSHM-CT-2006-0376331, LSHG-CT-2006-037277); the Biomedical Research Foundation of the Academy of Athens; the Hellenic Cardiological Society; the John F Kostopoulos Foundatio

Modified Laminar Bone in Ampelosaurus atacis and Other Titanosaurs (Sauropoda): Implications for Life History and Physiology

BACKGROUND: Long bone histology of the most derived Sauropoda, the Titanosauria suggests that titanosaurian long bone histology differs from the uniform bone histology of basal Sauropoda. Here we describe the long bone histology of the titanosaur Ampelosaurus atacis and compare it to that of basal neosauropods and other titanosaurs to clarify if a special titanosaur bone histology exists. METHODOLOGY/PRINCIPAL FINDINGS: Ampelosaurus retains the laminar vascular organization of basal Sauropoda, but throughout most of cortical growth, the scaffolding of the fibrolamellar bone, which usually is laid down as matrix of woven bone, is laid down as parallel-fibered or lamellar bone matrix instead. The remodeling process by secondary osteons is very extensive and overruns the periosteal bone deposition before skeletal maturity is reached. Thus, no EFS is identifiable. Compared to the atypical bone histology of Ampelosaurus, the large titanosaur Alamosaurus shows typical laminar fibrolamellar bone. The titanosaurs Phuwiangosaurus, Lirainosaurus, and Magyarosaurus, although differing in certain features, all show this same low amount or absence of woven bone from the scaffolding of the fibrolamellar bone, indicating a clear reduction in growth rate resulting in a higher bone tissue organization. To describe the peculiar primary cortical bone tissue of Phuwiangosaurus, Ampelosaurus, Lirainosaurus, and Magyarosaurus, we here introduce a new term, "modified laminar bone" (MLB). CONCLUSIONS/SIGNIFICANCE: Importantly, MLB is as yet not known from extant animals. At least in Lirainosaurus and Magyarosaurus the reduction of growth rate indicated by MLB is coupled with a drastic body size reduction and maybe also a reduction in metabolic rate, interpreted as a result of dwarfing on the European islands during the Late Cretaceous. Phuwiangosaurus and Ampelosaurus both show a similar reduction in growth rate but not in body size, possibly indicating also a reduced metabolic rate. The large titanosaur Alamosaurus, on the other hand, retained the plesiomorphic bone histology of basal neosauropods

The Development of a Content Analysis Model for Assessing Students’ Cognitive Learning in Asynchronous Online Discussions

The purpose of this study was to develop and validate a content analysis model for assessing students\u27 cognitive learning in asynchronous online discussions. It adopted a fully mixed methods design, in which qualitative and quantitative methods were employed sequentially for data analysis and interpretation. Specifically, the design was a sequential exploratory (QUAL→ quan) design with priority given to qualitative data and methods. Qualitative data were 800 online postings collected in two online courses. Quantitative data were 803 online postings from the same two courses but from different discussion topics and different weeks. During the qualitative process, a grounded theory approach was adopted to construct a content analysis model based on qualitative data. During the quantitative process, chi-square tests and confirmative factor analysis (CFA) which used online postings as cases or observations and was the first of its kind were performed to test if the new model fit the quantitative data