High prevalence of respiratory symptoms among workers in the development section of a manually operated coal mine in a developing country: A cross sectional study

Background  

Few studies of miners have been carried out in African countries; most are from South Africa, where the working conditions are assumed to be better than in the rest of Africa. Several studies have focused on respiratory disorders among miners, but development workers responsible for creating underground road ways have not been studied explicitly. This is the first study assessing the associations between exposure to dust and quartz and respiratory symptoms among coal mine workers in a manually operated coal mine in Tanzania, focusing on development workers, as they have the highest exposure to coal dust.     

Characterization of B-cell lines established from two X-linked severe combined immunodeficiency patients: interleukin-15 binds to the B cells but is not internalized efficiently

X-linked severe combined immunodeficiency (XSCID) is characterized by absent or profoundly reduced numbers of T cells and normal numbers of B cells in the circulation. Affected patients have mutations of the interleukin-2 (IL-2) receptor gamma chain gene. Using Epstein-Barr virus-transformed B-lymphoblastoid cell lines (B-LCLs) established from two unrelated XSCID patients, we could show that neither expressed the IL-2 receptor gamma chain on the cell surface. A novel cytokine IL-15, which has biologic activities similar to those of IL-2, could bind to the XSCID B-LCLs in the absence of the gamma chain, although both the beta and gamma chains of the human IL-2 receptor were previously shown to be required for IL-15 binding by transfected COS cells. Furthermore, a significant reduction and delay of IL-15 internalization by B lymphoblasts from XSCID patients was observed when compared with that of normal control B-LCLs. These results show the existence of a novel IL-15-specific receptor component that contributes to IL-15 binding but is insufficient for IL-15 internalization in the absence of the IL-2 receptor gamma chain.     

In vivo neutrophil and lymphocyte function studies in a patient with leukocyte adhesion deficiency type II

We investigated in vivo neutrophil and lymphocyte function in a patient who lacks Sialyl-Lewis-X, a ligand for the selectin family of leukocyte adhesion molecules (leukocyte adhesion deficiency II, LAD II). As assessed by skin chamber and skin window techniques, in vivo chemotaxis of neutrophils was markedly impaired (less than 6% of normal values). A marginal pool was present as determined by an increase in circulating neutrophils after epinephrine injection and calculated recovery of infused radiolabeled autologous neutrophils. Kinetic studies showed a reduced half-life of 3.2 hours (normal 7 hours) and markedly increased turnover rate (cells/kg/d) of approximately eight times the normal value. A normal antibody response to the T-cell-dependent antigen bacteriophage phi X174 showed that T/B-cell interaction is not affected in LAD II. These findings provide direct evidence that the selectin family and its ligands play an important role in neutrophil function.     

Missed opportunities for diagnosis: lessons learned from diagnostic errors in primary care

Background

Because of the difficulties inherent in diagnosis in primary care, it is inevitable that diagnostic errors will occur. However, despite the important consequences associated with diagnostic errors and their estimated high prevalence, teaching and research on diagnostic error is a neglected area.

Aim

To ascertain the key learning points from GPs’ experiences of diagnostic errors and approaches to clinical decision making associated with these.

Design and setting

Secondary analysis of 36 qualitative interviews with GPs in Oxfordshire, UK.

Method

Two datasets of semi-structured interviews were combined. Questions focused on GPs’ experiences of diagnosis and diagnostic errors (or near misses) in routine primary care and out of hours. Interviews were audiorecorded, transcribed verbatim, and analysed thematically.

Results

Learning points include GPs’ reliance on ‘pattern recognition’ and the failure of this strategy to identify atypical presentations; the importance of considering all potentially serious conditions using a ‘restricted rule out’ approach; and identifying and acting on a sense of unease. Strategies to help manage uncertainty in primary care were also discussed.

Conclusion

Learning from previous examples of diagnostic errors is essential if these events are to be reduced in the future and this should be incorporated into GP training. At a practice level, learning points from experiences of diagnostic errors should be discussed more frequently; and more should be done to integrate these lessons nationally to understand and characterise diagnostic errors.     

Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment

Expression of the granulocyte-macrophage colony-stimulating factor (GM- CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.     

HD‐CAB: A cognitive assessment battery for clinical trials in Huntington's disease1,2,3

Cognitive dysfunction is central to Huntington's disease (HD) and undermines quality of life. Clinical trials are now targeting cognitive outcomes in HD; however, no cognitive battery has been optimized for HD clinical trials. We evaluated 16 cognitive tests in a 20‐site, five‐country, observational study designed to mimic aspects of a clinical trial (e.g., data collection managed by a contract research organization, repeated testing, prespecified statistical analyses). Fifty‐five early HD, 103 premanifest HD (pre‐HD), and 105 controls were tested at visit 1, visit 2 (1‐3 days later), and visit 3 (5‐7 weeks after visit 1). For inclusion in a recommended battery, tests were evaluated for sensitivity, practice effects, reliability, domain coverage, feasibility, and tolerability. Most tests differentiated controls from pre‐HD and early HD and showed excellent psychometric properties. We selected six tests to constitute the Huntington's Disease Cognitive Assessment Battery (HD‐CAB): Symbol Digit Modalities Test, Paced Tapping, One Touch Stockings of Cambridge (abbreviated), Emotion Recognition, Trail Making B, and the Hopkins Verbal Learning Test. These tests demonstrated sensitivity to disease status (Cohen's d effect sizes: early HD= ?1.38 to ?1.90 and pre‐HD= ?0.41 to ?0.78), and acceptable reliability (r's 0.73‐0.93). A composite score yielded large effect sizes (early HD = ?2.44 and pre‐HD = ?0.87) and high reliability (r = 0.95). HD‐CAB is the first cognitive battery designed specifically for use in late premanifest and early HD clinical trials. Adoption of the HD‐CAB will facilitate evaluation of treatments to improve cognition in HD. © 2014 International Parkinson and Movement Disorder Society     

Seeing the Wood for the Trees: A Minimal Reference Phylogeny for the Human Y Chromosome

During the last few decades, a wealth of studies dedicated to the human Y chromosome and its DNA variation, in particular Y‐chromosome single‐nucleotide polymorphisms (Y‐SNPs), has led to the construction of a well‐established Y‐chromosome phylogeny. Since the recent advent of new sequencing technologies, the discovery of additional Y‐SNPs is exploding and their continuous incorporation in the phylogenetic tree is leading to an ever higher resolution. However, the large and increasing amount of information included in the “complete” Y‐chromosome phylogeny, which now already includes many thousands of identified Y‐SNPs, can be overwhelming and complicates its understanding as well as the task of selecting suitable markers for genotyping purposes in evolutionary, demographic, anthropological, genealogical, medical, and forensic studies. As a solution, we introduce a concise reference phylogeny whereby we do not aim to provide an exhaustive tree that includes all known Y‐SNPs but, rather, a quite stable reference tree aiming for optimal global discrimination capacity based on a strongly reduced set that includes only the most resolving Y‐SNPs. Furthermore, with this reference tree, we wish to propose a common standard for Y‐marker as well as Y‐haplogroup nomenclature. The current version of our tree is based on a core set of 417 branch‐defining Y‐SNPs and is available online at http://www.phylotree.org/Y .     

Combination of short CAG and GGN repeats in the androgen receptor gene is associated with acne risk in North East China

Background Acne vulgaris is one of the most common skin disorders, and androgen is known to play a key role in the development of acne. However, the exact genetic mechanism by which androgen receptor (AR) gene affects acne development is still unclear. Objective Our study aimed to investigate whether CAG and GGN polymorphism of the AR gene are associated with acne risk. Patients and methods Two hundred thirty‐eight patients and 207 controls were included in the study. The repeat lengths of the AR gene were determined by GeneScan analysis. Results Men with CAG < 23 and women with CAG < 24 had significant risk compared to those men with CAG ≥ 23 [odds ratio (OR), 2.07; 95% confidence interval (95% CI), 1.21–3.54] and women with CAG ≥ 24 (OR, 2.05; 95% CI, 1.18–3.56). In males, GGN repeats, considered independently of the CAG repeat, have no significant effect on the acne risk; however, when combined with CAG repeats, the acne patients exhibited significantly higher frequency of the haplotypes CAG < 23/GGN ≤ 23 (OR, 3.33; 95% CI, 1.10–10.07; P < 0.05) compared with the controls. Conclusion Our results of this study strongly indicated that a shorter CAG repeat length and specific haplotypes of AR attributed to the risk of acne development and thus could serve as a susceptibility marker.