Coding haplotype analysis supports HCR as the putative susceptibility gene for psoriasis at the MHC PSORS1 locus

PSORS1, near HLA-C, is the major genetic determinant of psoriasis. We present genetic and structural evidence suggesting a major role for the HCR gene at the PSORS1 locus. Genotyping of 419 families from six populations revealed that coding single-nucleotide polymorphisms of HCR formed a conserved allele HCR*WWCC that associated highly significantly with psoriasis and with the HLA-Cw6 allele in all populations. Because of strong linkage disequilibrium between HLA-Cw6 and HCR*WWCC, the two genes could not be genetically distinguished by this sample size. However, the variant HCR allele was predicted to differ in secondary structure from the wild-type protein. HCR protein expression in lesional psoriatic skin differed considerably from that observed in normal skin. These results provide strong evidence for the HCR*WWCC allele as a major genetic determinant for psoriasis, probably by a mechanism impacting on keratinocyte proliferation.     

Upper and lower gastrointestinal endoscopical investigation in elderly patients with iron deficiency anaemia

Iron deficiency anaemia is frequently observed in male adults and postmenopausal women due to chronic occult bleeding, usually from the gastrointestinal tract. Practically, as endoscopical investigation of the gastrointestinal system is an invasive procedure, iron replacement treatment was generally started without investigation of the underlying aetiology even in first-line health institutions. This study evaluates the role of endoscopy in the investigation of the aetiology of anaemia in 95 patients (51 males, 44 females), aged 64.9+/-12.5 years (range 50-90 years). All patients having iron deficiency anaemia were investigated by upper gastrointestinal endoscopy and colonoscopy. Upper and lower gastrointestinal pathologies were seen in 10 (10.6%) and 55 (57.8%) patients, respectively. However, no gastrointestinal lesion was found in 30 (31.6%) patients with iron deficiency anaemia. Out of the 95 patients, 16 (16.9%) had erosive gastritis, 15 (15.8%) duodenal ulcer, 8 (8.4%) gastric ulcer, 7 (7.3%) gastric tumours, 7 (7.3%) oesophagitis. 5 (5.4%) colon tumours, 3 (3.2%) haemorrhoids, 2 (2.1%) non-tropical sprue, 1 (1%) colonic polyp, and 1 (1%) colitis. In the majority of elderly patients with iron deficiency anaemia, upper gastrointestinal system disease was found. In 12 (12.7%) patients in the study group, malignancies were detected. In elderly patients with iron deficiency anaemia, the aetiology should be highlighted before giving iron supplementation.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia

Copy number variations (CNVs) account for a substantial proportion of human genomic variation, and have been shown to cause neurodevelopmental disorders. We sought to determine the relevance of CNVs to the aetiology of schizophrenia (SZ). Whole-genome, high-resolution, tiling path BAC array comparative genomic hybridization (array CGH) was employed to test DNA from 93 individuals with DSM-IV SZ. Common DNA copy number changes that are unlikely to be directly pathogenic in SZ were filtered out by comparison to a reference dataset of 372 control individuals analyzed in our laboratory, and a screen against the Database of Genomic Variants. The remaining aberrations were validated with Affymetrix 250K SNP arrays or 244K Agilent oligo-arrays and tested for inheritance from the parents. A total of 13 aberrations satisfied our criteria. Two of them are very likely to be pathogenic. The first one is a deletion at 2p16.3 that was present in an affected sibling and disrupts NRXN1. The second one is a de novo duplication at 15q13.1 spanning APBA2. The proteins of these two genes interact directly and play a role in synaptic development and function. Both genes have been affected by CNVs in patients with autism and mental retardation, but neither has been previously implicated in SZ.     

Enhancing behavioral science education at the Ohio State University College of Medicine.

The social and behavioral sciences play key roles in patient health outcomes. Given this reality, successful development of social and behavioral science curricula in medical education is critically important to the quality of patients' lives and the effectiveness of health care delivery systems. The Institute of Medicine, in a recent report, recommended that medical schools enhance their curricula in these areas and identified four institutions as "exemplars" of social and behavioral science education. The authors describe an ongoing curriculum development and improvement process that produced one such exemplary program at The Ohio State University College of Medicine.The authors provide a historical perspective on behavioral science education, discuss issues that led to curricular change, and describe the principles and processes used to implement reform. Critical factors underlying positive change are addressed: increase active learning, recruit a core group of small-group facilitators who are primary care physicians, diversify teaching methods, support student-directed educational initiatives, enhance student-teacher relationships, centralize course administration, obtain funding, implement a faculty development program, and apply curriculum quality improvement methods. Outcome data from evaluations completed by both students and small-group physician faculty are presented, and future directions regarding further revision are outlined. The authors believe that the strategies they describe can be applied at other institutions and assist behavioral science educators who may experience the challenges typically encountered in this important field of medical education.     

Association of mast cells with microvessel density in urothelial carcinomas of the urinary bladder

This study aims to investigate the relation of mast cell (MC) accumulation with tumor grade and stage in urothelial carcinomas of the urinary bladder and to determine its relationship with angiogenesis. A total of 78 urothelial carcinomas obtained by transurethral resection were investigated immunohistochemically by using c-Kit (CD117) and anti-CD34. The correlation between MC counts and microvessels was evaluated and compared with histopathologic parameters including tumor stage and grade. There were significant correlations between MC counts, grade, and stage (P < .05; r = 0.69 and 0.63, respectively). However, MC counts in adjacent nontumoral bladder mucosa significantly were higher than the MC counts in tumoral zone (P < .001). On the other hand, significant correlation was found between the number of MCs in tumoral zone and the microvessel density (P < .05, r = 0.56). The results of our study suggest that c-Kit positive MCs in tumoral zone may contribute to tumor angiogenesis and play a significant role in tumor growth and invasion. Further studies are needed to support these observations.     

Kinship,dispersal and hantavirus transmission in bank and common voles

Hantaviruses are among the main emerging infectious agents in Europe. Their mode of transmission in natura is still not well known. In particular, social features and behaviours could be crucial for understanding the persistence and the spread of hantaviruses in rodent populations. Here, we investigated the importance of kinclustering and dispersal in hantavirus transmission by combining a fine-scale spatiotemporal survey (4 km²) and a population genetics approach. Two specific host-hantavirus systems were identified and monitored: the bank vole Myodes, earlier Clethrionomys glareolus––Puumala virus and the common vole Microtus arvalis—Tula virus. Sex, age and landscape characteristics significantly influenced the spatial distribution of infections in voles. The absence of temporal stability in the spatial distributions of viruses suggested that dispersal is likely to play a role in virus propagation. Analysing vole kinship from microsatellite markers, we found that infected voles were more closely related to each other than non-infected ones. Winter kin-clustering, shared colonies within matrilineages or delayed dispersal could explain this pattern. These two last results hold, whatever the host-hantavirus system considered. This supports the roles of relatedness and dispersal as general features for hantavirus transmission. N. Charbonnel and J.-F. Cosson have contributed equally.     

Investigating in vivo airway wall mechanics during tidal breathing with optical coherence tomography

Optical coherence tomography (OCT) is a nondestructive imaging technique offering high temporal and spatial resolution, which makes it a natural choice for assessing tissue mechanical properties. We have developed methods to mechanically analyze the compliance of the rabbit trachea in vivo using tissue deformations induced by tidal breathing, offering a unique tool to assess the behavior of the airways during their normal function. Four-hundred images were acquired during tidal breathing with a custom-built endoscopic OCT system. The surface of the tissue was extracted from a set of these images via image processing algorithms, filtered with a bandpass filter set at respiration frequency to remove cardiac and probe motion, and compared to ventilatory pressure to calculate wall compliance. These algorithms were tested on elastic phantoms to establish reliability and reproducibility. The mean tracheal wall compliance (in five animals) was 1.3±0.3×10(-5) (mm Pa)(-1). Unlike previous work evaluating airway mechanics, this new method is applicable in vivo, noncontact, and loads the trachea in a physiological manner. The technique may have applications in assessing airway mechanics in diseases such as asthma that are characterized by significant airway remodeling.     

Medical and psychology students' self-assessed communication skills: A pilot study

Objective

The purpose of this study was to describe how psychology and medical students assess their own competency and skills before and after training, in which role-play was used to teach interpersonal and communication skills.

Method

Interpersonal and communication skills were assessed with a semi-structured questionnaire before and after the training.

Results

The students of both medicine and psychology estimated their skill levels to be higher after the course. The psychology students estimated their skills for communication, motivating interviewing, empathy and reflection, and change orientation to be better at the end of the course. Medical students estimated their communication skills, motivating interviewing skills, and change orientation skills to be better at the end of the course.

Conclusion

Even a short period of training in interpersonal and communication skills can positively affect the self-assessed skills of the medical students.

Practice implications

In the future, it would be worthwhile to pay attention to reflective teaching practices in the training of both medical and psychology students. The cognitive and emotional components of these practices help students to develop their own communication skills.