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Biallelic mutations in LIG4 encoding DNA-ligase 4 cause a rare immunodeficiency syndrome manifesting as infant-onset life-threatening and/or opportunistic infections, skeletal malformations, radiosensitivity and neoplasia. LIG4 is pivotal during DNA repair and during V(D)J recombination as it performs the final DNA-break sealing step. This study explored whether monoallelic LIG4 missense mutations may underlie immunodeficiency and autoimmunity with autosomal dominant inheritance. Extensive flow-cytometric immune-phenotyping was performed. Rare variants of immune system genes were analyzed by whole exome sequencing. DNA repair functionality and T-cell–intrinsic DNA damage tolerance was tested with an ensemble of in vitro and in silico tools. Antigen-receptor diversity and autoimmune features were characterized by high-throughput sequencing and autoantibody arrays. Reconstitution of wild-type versus mutant LIG4 were performed in LIG4 knockout Jurkat T cells, and DNA damage tolerance was subsequently assessed. A novel heterozygous LIG4 loss-of-function mutation (p.R580Q), associated with a dominantly inherited familial immune-dysregulation consisting of autoimmune cytopenias, and in the index patient with lymphoproliferation, agammaglobulinemia, and adaptive immune cell infiltration into nonlymphoid organs. Immunophenotyping revealed reduced naive CD4+ T cells and low TCR-Vα7.2+ T cells, while T-/B-cell receptor repertoires showed only mild alterations. Cohort screening identified 2 other nonrelated patients with the monoallelic LIG4 mutation p.A842D recapitulating clinical and immune-phenotypic dysregulations observed in the index family and displaying T-cell–intrinsic DNA damage intolerance. Reconstitution experiments and molecular dynamics simulations categorize both missense mutations as loss-of-function and haploinsufficient. This study provides evidence that certain monoallelic LIG4 mutations may cause human immune dysregulation via haploinsufficiency. [ABSTRACT FROM AUTHOR]

Pascal Bovet1, Philippe Hirsiger2, Frédéric Emery3, Jessica De Bernardini2, Christophe Rossier3, Josefine Trebeljahr2, Isabelle Hagon-Traub21Institute of Social and Preventive Medicine (IUMSP), University of Lausanne and Centre Universitaire Hospitalier Vaudois (CHUV), Lausanne, Switzerland; 2Public Health Service, Department of Health and Social Action, Canton of Vaud, Lausanne, Switzerland; 3Association of Pharmacists, Canton of Vaud, Lausanne, SwitzerlandBackground: Community-based diabetes screening programs can help sensitize the population and identify new cases. However, the impact of such programs is rarely assessed in high-income countries, where concurrent health information and screening opportunities are common place.Intervention and methods: A 2-week screening and awareness campaign was organized as part of a new diabetes program in the canton of Vaud (population of 697,000) in Switzerland. Screening was performed without appointment in 190 out of 244 pharmacies in the canton at the subsidized cost of 10 Swiss Francs per participant. Screening included questions on risk behaviors, measurement of body mass index, blood pressure, blood cholesterol, random blood glucose (RBG), and A1c if RBG was ≥7.0 mmol/L. A mass media campaign promoting physical activity and a healthy diet was channeled through several media, eg, 165 spots on radio, billboards in 250 public places, flyers in 360 public transport vehicles, and a dozen articles in several newspapers. A telephone survey in a representative sample of the population of the canton was performed after the campaign to evaluate the program.Results: A total of 4222 participants (0.76% of all persons aged ≥18 years) underwent the screening program (median age: 53 years, 63% females). Among participants not treated for diabetes, 3.7% had RBG ≥ 7.8 mmol/L and 1.8% had both RBG ≥ 7.0 mmol/L and A1c ≥ 6.5. Untreated blood pressure ≥140/90 mmHg and/or untreated cholesterol ≥5.2 mmol/L were found in 50.5% of participants. One or several treated or untreated modifiable risk factors were found in 78% of participants. The telephone survey showed that 53% of all adults in the canton were sensitized by the campaign. Excluding fees paid by the participants, the program incurred a cost of CHF 330,600.Conclusion: A community-based screening program had low efficiency for detecting new cases of diabetes, but it identified large numbers of persons with elevated other cardiovascular risk factors. Our findings suggest the convenience of A1c for mass screening of diabetes, the usefulness of extending diabetes screening to other cardiovascular risk factors, and the importance of a robust background communication campaign.Keywords: hypertension, cholesterol, community-based program, evaluation, Switzerland

Pascal Bovet, Philippe Hirsiger, Frédéric Emery, Jessica De Bernardini, Christophe Rossier, Josefine Trebeljahr, Isabelle Hagon-Traub. Impact and cost of a 2-week community-based screening and awareness program for diabetes and cardiovascular risk factors in a Swiss canton. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy 2011;4:213-223Original Article

Background Chronic anterior sternoclavicular (SC) instability is a rare but potentially disabling condition. It can arise in conjunction with trauma or hyperlaxity, or both. Numerous surgical techniques have been described, but no gold standard exists. SC instability is often position-dependent and can be reduced with the arm in a specific position. Methods To directly address this issue, we used a technique of corrective osteotomy of the clavicle with the goal to reorient the articular portion of the medial end of the clavicle so that it remains stable in all functional positions of the arm. To illustrate the technique and the correction in space, we performed postoperative 3-dimensional computed tomography analyses of the shoulder girdle of 4 patients. Clinical scores were obtained at the final follow-up and compared with preoperative scores. Results Mean follow-up was 64 months (range, 19-191 months). The mean Constant score improved from 58 (range, 45-68) preoperatively to 73 (range, 69-84) postoperatively and the Subjective Shoulder Value from 42 (range, 15-80) to 79 (range, 50-100). All patients reported good or very good stability of the SC joint at the last follow-up. We recorded no intraoperative or direct postoperative complications. During follow-up, 3 patients underwent removal of the plate, 1 of them for plate breakage. The mean postoperative correction for combined rotations is given as a 3-dimensional angle and averaged 28.0° (range, 8.6°-39.7°). Conclusion In this pilot study, medial corrective clavicular osteotomy using the described technique treated anterior SC instability with improvement of clinical shoulder function scores and good patient satisfaction. The technique appears simple and safe and deserves further evaluation. [ABSTRACT FROM AUTHOR]

Three-dimensional computer-assisted preoperative planning, combined with patient-specific surgical guides, has become an effective technique for treating complex extra- and intraarticular bone malunions by corrective osteotomy. The feasibility and accuracy of such a technique has not yet been evaluated for ankle deformities. Four surgical cases of varying complexity and location were selected for evaluation. Three-dimensional bone models of the affected and contralateral healthy lower limb were generated from computed tomography scans. The preoperative planning software permitted quantification of the deformity in 3 dimensions and subsequent simulation of reduction, yielding a precise surgical plan. Patient-specific surgical guides were designed, manufactured, and finally applied during surgery to reproduce the preoperative plan. Evaluation of the postoperative computed tomography scans indicated adequate reduction accuracy with residual translational and rotational errors of <3 mm and <6°, respectively. Two patients required revision surgery owing to anterior osseous impingement or delayed union of the osteotomy. All patients were satisfied with the postoperative course and were pain free at a mean follow-up period of 2.5 (range 1 to 4) years. These promising results require confirmation in a clinical study with a larger sample size. [ABSTRACT FROM AUTHOR]

We present the case of a 31-year-old woman who was referred with a 12-month history of a tumor on the ulnar side of her dominant right hand. The eventual histopathologic diagnosis was an atypical pleomorphous lipomatous tumor, an entity that has only been recently classified in the World Health Organization Classification of Soft Tissue and Bone Tumors. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial consumption in veterinary medicine is of great importance. Increased awareness by the public and media has led to demands for decreased use of antimicrobials in pigs. This study aimed to identify risk factors for regular oral antimicrobial consumption in Swiss fattening pig farms, and to quantify the amount of antimicrobial active substances administered orally to pigs at the farm level., Results: A case-control study was performed on 99 fattening farms between May 2014 and January 2015. Seventy-two case farms (with oral group treatment of antimicrobials in at least 50 % of pigs) and 27 control farms (with no regular oral group treatment) were visited once during the study. Data about potential risk factors and antimicrobial consumption were collected by questionnaire. Antimicrobial consumption was recorded and treatment incidence (TI) was calculated for all farms over a one year period. Sulphonamides and tetracyclines were the antimicrobials consumed in the greatest quantity. The median TI for oral antimicrobial use in the case group was 224.7. In the control group, the median TI was 0 for oral antimicrobial use, with values ranging from 0 to 140.1. In a multivariable regression model, seven risk factors associated with regular oral antimicrobial group treatment were identified: mixing pigs from different suppliers within the same pen, absence of a work protocol that ensures treating of healthy pigs before sick pigs, distance to next pig farm < 500 metres, external analysis of production parameters, no availability of dirty visitor boots, the farmer not working on other farms, and no application of homoeopathic agents., Conclusions: The results of this study point out the importance of increasing farmers' awareness of good farming practices and biosecurity. Important recommendations for decreasing oral antimicrobial consumption identified by this study include avoiding mixing pigs from different suppliers in the same pen and strictly handling sick pigs after healthy ones. Improvements in these areas could enhance the overall health of pigs and thereby reduce the consumption of antimicrobials on pig farms.

In the present study, risk factors for the use of oral antibiotics in weaned piglets were collected on 112 pig farms by a personal questionaire. The most common indication for an antibiotic group therapy was diarrhoea, and the most frequently used antibiotic was Colistin. On average, 27.33 daily doses in the control farms and 387.21 daily doses in the problem farms per 1000 weaners were administered on a given day. The significant risk factors in the multivariate model were poor hygiene in the water supply of suckling piglets, less than two doses ofprestarter feed daily, lack of an all-in-and-all-out production system in weaners, no herd book performance data analysis, and less than two of the legally prescribed veterinary visits per year. Furthermore, the treatment incidence of weaners for oral antibiotics was calculated on the basis of the drug inventory. This study provides evidence that the use of oral antibiotics in weaners can be reduced by interventions in hygiene and management.

The attitude as well as the expertise of a person affect the behavior and actions in daily life. To investigate the influence of attitude and knowledge of pig producers on the use of antibiotics in farms, 220 Swiss pig producers were questioned on health awareness, attitude towards sustainable production, risk behavior, intrinsic motivation and knowledge about antibiotics and resistance development. In addition, the strategy of antibiotic use (therapeutic or prophylactic) and the business practice (single or group therapy) for the amount of antibiotics on one hand and for the risk of antibiotic resistance development on the other hand, were determined in a personal interview. Farmers using antibiotics only therapeutically had a better business practice. A direct link between the personal attitude and the antibiotic use or a higher risk of development of antibiotic resistance was not found in this investigation.