Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation

© 2016 Taylor & Francis. Osteogenesis imperfecta (OI) is a heterogeneous group of inherited disorders of bone formation, resulting in low bone mass and an increased propensity to fracture. Over 90% of patients with OI have a mutation in COL1A1/COL1A2, which shows an autosomal dominant pattern of inheritance. In-depth phenotyping and in particular, studies involving manifestations in the skin connective tissue have not previously been undertaken in OI. The aims of the study were to perform histological and ultrastructural examination of skin biopsies in a cohort of patients with OI; to identify common and distinguishing features in order to inform genotype-phenotype correlation; and to identify common and distinguishing features between the different subtypes of OI. As part of the RUDY (Rare Diseases in Bone, Joints and/or Blood Vessels) study, in collaboration with the NIHR Rare Diseases Translational Research Collaboration, we undertook a national study of skin biopsies in patients with OI. We studied the manifestations in the skin connective tissue and undertook in-depth clinical and molecular phenotyping of 16 patients with OI. We recruited 16 patients: analyses have shown that in type 1 collagen mutation positive patients (COL1A1/ COL1A2) (n-4/16) consistent findings included: variable collagen fibril diameter (CFD) and presence of collagen flowers. Histological examination in these patients showed an increase in elastic fibers that are frequently fragmented and clumped. These observations provide evidence that collagen flowers and CFD variability are consistent features in OI due to type 1 collagen defects and reinforce the need for accurate phenotyping in conjunction with genomic analyses

Higher Doses of Subcutaneous IgG Reduce Resource Utilization in Patients with Primary Immunodeficiency

The recommended dose of IgG in primary immunodeficiency (PID) has been increasing since its first use. This study aimed to determine if higher subcutaneous IgG doses resulted in improved patient outcomes by comparing results from two parallel clinical studies with similar design. One patient cohort received subcutaneous IgG doses that were 1.5 times higher than their previous intravenous doses (mean 213 mg/kg/week), whereas the other cohort received doses identical to previous subcutaneous or intravenous doses (mean 120 mg/kg/week). While neither cohort had any serious infections, the cohort maintained on higher mean IgG dose had significantly lower rates of non-serious infections (2.76 vs. 5.18 episodes/year, P < 0.0001), hospitalization (0.20 vs. 3.48 days/year, P < 0.0001), antibiotic use (48.50 vs. 72.75 days/year, P < 0.001), and missed work/school activity (2.10 vs. 8.00 days/year, P < 0.001). The higher-dose cohort had lower health care utilization and improved indices of well being compared to the cohort treated with traditional IgG doses

What are the important components of the clinical assessment of hand problems in older adults in primary care? Results of a Delphi study

<p>Abstract</p> <p>Background</p> <p>To identify clinical questions and assessments regarded by health care practitioners as important when assessing undifferentiated hand pain or problems in adults aged 50 years and over presenting to primary care.</p> <p>Methods</p> <p>A purposively selected panel of 26 UK-based Health Care Practitioners comprising occupational therapists, physiotherapists, rheumatologists and general practitioners, were invited to take part in a consensus study involving three postal rounds of a Delphi questionnaire with accompanying case scenarios. Participants were asked to generate questions and assessments (round 1), rate their importance (round 2), and vote on which items were most important (round 3).</p> <p>Results</p> <p>Sixteen Health Care Practitioners agreed to participate with 11 completing all three rounds. The first round of the Delphi study generated 156 questions and 143 assessments. After three rounds agreement was reached on the importance of 25 questions and 19 assessments. Questions were weighted towards current symptoms, but also included the history of previous hand problems, self-reported hand function, co-morbidity and general health. Observation and palpation of features predominated in the choice of assessment, but specific tests, grip strength, evaluation of sensation and hand function were also included.</p> <p>Conclusions</p> <p>A pool of clinical questions and assessments were generated by Health Care Practitioners, and those considered most important for assessing older adults presenting with undifferentiated hand pain and hand problems in primary care were identified. Further evaluation is required to establish the reliability and feasibility of using these questions and assessments in primary care. In particular, the relative contribution of these questions and assessments in evaluating the nature and severity of hand problems, assisting diagnosis, indicating appropriate management, and predicting future course requires further investigation.</p

Oncolytic Measles Virotherapy and Opposition to Measles Vaccination

Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination

Differentiating between monozygotic twins through methylation specific high resolution melt curve analysis

Whilst DNA profiling is an extremely powerful human identification tool, it is limited when it comes to monozygotic (MZ) or identical twins, where in such cases they would exhibit the same DNA profile. This creates issues where the suspect is one of the twins. Currently, efforts are being made to resolve this through whole genome or next generation sequencing, which can be very expensive. This study explores the feasibility of using high resolution melt curve analysis to characterize the DNA methylation status. DNA methylation can be altered by environmental factors, consequently over the life of monozygotic twins; they can end up with differing DNA methylation patterns, typically characterized by sequencing. Buccal swabs were collected from five sets of MZ twins of differing ages, as well as from a full sibling (non-MZ). All samples underwent DNA extraction, bi-sulfite treatment, amplification and then underwent high resolution melt curve analysis using a 7500 Fast Real-Time PCR machine, targeting a section of the Alu-SP region and the promoter region of the E2F3 gene. Significantly different melting temperatures (Tm) were obtained in four of the five MZ twins of the alu- SP samples, as well as in the non-MZ full sibling samples, and all 5 twin sets of samples analysing the E2F3 fragment; thus indicating that a relatively cheaper faster test could be used to differentiate between MZ twins in a forensic context

Dissemination of Competitive Intelligence

The paper argues that competitive intelligence is a vital function and attempts to study how it is distributed, especially by technologies, within organizations. Related topics, the sources of competitive intelligence, and who distributes and receives competitive intelligence, are also addressed. A literature-based study is extended by a quantitative survey of members of the Society of Competitive Information Professionals (SCIP) and email interviews with a self-chosen sample of respondees. The paper concludes that the distribution of competitive intelligence can be aided by technology but to be effective must be primarily 'person-focused'. Competitive intelligence itself needs to be seen as a form of knowledge management rather than an information provision function. This has implications for sources and for the professional roots of those who provide competitive intelligence. Evaluation of competitive information provision is seen as a next step for research