Prevalence and risk factors of late presentation for HIV diagnosis and care in a tertiary referral centre in Switzerland.

QUESTIONS UNDER STUDY We sought to identify reasons for late human immunodeficiency virus (HIV) testing or late presentation for care. METHODS A structured chart review was performed to obtain data on test- and health-seeking behaviour of patients presenting late with CD4 cell counts below 350 cells/µl or with acquired immunodeficiency syndrome (AIDS), at the Zurich centre of the Swiss HIV Cohort Study between January 2009 and December 2011. Logistic regression analyses were used to compare demographic characteristics of persons presenting late with not late presenters. RESULTS Of 281 patients, 45% presented late, 48% were chronically HIV-infected non-late presenters, and an additional 7% fulfilled the <350 CD4 cells/µl criterion for late presentation but a chart review revealed that lymphopenia was caused by acute HIV infection. Among the late presenters, 60% were first tested HIV positive in a private practice. More than half of the tests (60%) were suggested by a physician, only 7% following a specific risk situation. The majority (88%) of patients entered medical care within 1 month of testing HIV positive. Risk factors for late presentation were older age (odds ratio [OR] for ≥50 vs <30 years: 3.16, p = 0.017), Asian versus Caucasian ethnicity (OR 3.5, p = 0.021). Compared with men who have sex with men (MSM) without stable partnership, MSM in a stable partnership appeared less likely to present late (OR 0.50, p = 0.034), whereas heterosexual men in a stable partnership had a 2.72-fold increased odds to present late (p = 0.049). CONCLUSIONS The frequency of late testing could be reduced by promoting awareness, particularly among older individuals and heterosexual men in stable partnerships.

Genetic and microbial factors modulating the ubiquitin proteasome system in inflammatory bowel disease

OBJECTIVE: Altered microbiota composition, changes in immune responses and impaired intestinal barrier functions are observed in IBD. Most of these features are controlled by proteases and their inhibitors to maintain gut homeostasis. Unrestrained or excessive proteolysis can lead to pathological gastrointestinal conditions. The aim was to validate the identified protease IBD candidates from a previously performed systematic review through a genetic association study and functional follow-up. DESIGN: We performed a genetic association study in a large multicentre cohort of patients with Crohn's disease (CD) and UC from five European IBD referral centres in a total of 2320 CD patients, 2112 UC patients and 1796 healthy controls. Subsequently, we did an extensive functional assessment of the candidate genes to explore their causality in IBD pathogenesis. RESULTS: Ten single nucleotide polymorphisms (SNPs) in four genes were significantly associated with CD: CYLD, USP40, APEH and USP3. CYLD was the most significant gene with the intronically located rs12324931 the strongest associated SNP (pFDR=1.74e-17, OR=2.24 (1.83 to 2.74)). Five SNPs in four genes were significantly associated with UC: USP40, APEH, DAG1 and USP3. CYLD, as well as some of the other associated genes, is part of the ubiquitin proteasome system (UPS). We therefore determined if the IBD-associated adherent-invasive Escherichia coli (AIEC) can modulate the UPS functioning. Infection of intestinal epithelial cells with the AIEC LF82 reference strain modulated the UPS turnover by reducing poly-ubiquitin conjugate accumulation, increasing 26S proteasome activities and decreasing protein levels of the NF-κB regulator CYLD. This resulted in IκB-α degradation and NF-κB activation. This activity was very important for the pathogenicity of AIEC since decreased CYLD resulted in increased ability of AIEC LF82 to replicate intracellularly. CONCLUSIONS: Our results reveal the UPS, and CYLD specifically, as an important contributor to IBD pathogenesis, which is favoured by both genetic and microbial factors.

Spatial and temporal patterns of greenness on the Yamal Peninsula, Russia: interactions of ecological and social factors affecting the Arctic normalized difference vegetation index

The causes of a greening trend detected in the Arctic using the normalized difference vegetation index (NDVI) are still poorly understood. Changes in NDVI are a result of multiple ecological and social factors that affect tundra net primary productivity. Here we use a 25 year time series of AVHRR-derived NDVI data (AVHRR: advanced very high resolution radiometer), climate analysis, a global geographic information database and ground-based studies to examine the spatial and temporal patterns of vegetation greenness on the Yamal Peninsula, Russia. We assess the effects of climate change, gas-field development, reindeer grazing and permafrost degradation. In contrast to the case for Arctic North America, there has not been a significant trend in summer temperature or NDVI, and much of the pattern of NDVI in this region is due to disturbances. There has been a 37% change in early-summer coastal sea-ice concentration, a 4% increase in summer land temperatures and a 7% change in the average time-integrated NDVI over the length of the satellite observations. Gas-field infrastructure is not currently extensive enough to affect regional NDVI patterns. The effect of reindeer is difficult to quantitatively assess because of the lack of control areas where reindeer are excluded. Many of the greenest landscapes on the Yamal are associated with landslides and drainage networks that have resulted from ongoing rapid permafrost degradation. A warming climate and enhanced winter snow are likely to exacerbate positive feedbacks between climate and permafrost thawing. We present a diagram that summarizes the social and ecological factors that influence Arctic NDVI. The NDVI should be viewed as a powerful monitoring tool that integrates the cumulative effect of a multitude of factors affecting Arctic land-cover change.

Vitamin D time profile based on the contribution of non-genetic and genetic factors in HIV-infected individuals of European ancestry

BACKGROUND Vitamin D deficiency is prevalent in HIV-infected individuals and vitamin D supplementation is proposed according to standard care. This study aimed at characterizing the kinetics of 25(OH)D in a cohort of HIV-infected individuals of European ancestry to better define the influence of genetic and non-genetic factors on 25(OH)D levels. These data were used for the optimization of vitamin D supplementation in order to reach therapeutic targets. METHODS 1,397 25(OH)D plasma levels and relevant clinical information were collected in 664 participants during medical routine follow up visits. They were genotyped for 7 SNPs in 4 genes known to be associated with 25(OH)D levels. 25(OH)D concentrations were analyzed using a population pharmacokinetic approach. The percentage of individuals with 25(OH)D concentrations within the recommended range of 20-40ng/ml during 12 months of follow up and several dosage regimens were evaluated by simulation. RESULTS A one-compartment model with linear absorption and elimination was used to describe 25(OH)D pharmacokinetics, while integrating endogenous baseline plasma concentrations. Covariate analyses confirmed the effect of seasonality, body mass index, smoking habits, the analytical method, darunavir/r and the genetic variant in GC (rs2282679) on 25(OH)D concentrations. 11% of the interindividual variability in 25(OH)D levels was explained by seasonality and other non-genetic covariates and 1% by genetics. The optimal supplementation for severe vitamin D deficient patients was 300000 IU two times per year. CONCLUSIONS This analysis allowed identifying factors associated with 25(OH)D plasma levels in HIV-infected individuals. Improvement of dosage regimen and timing of vitamin D supplementation is proposed based on those results.

Mitochondrial outer membrane proteome of Trypanosoma brucei reveals macromolecular transport machineries and novel factors required to maintain mitochondrial morphology

The mitochondrial outer membrane (MOM) separates the mitochondria from the cytoplasm, serving both as a barrier and as a gateway. Protein complexes — believed to be universally conserved in all eukaryotes — reside in the MOM to orchestrate and control metabolite exchange, lipid metabolism and uptake of biopolymers such as protein and RNA. African trypanosomes are the causative agent of the sleeping sickness in humans. The parasites are among the earliest diverging eukaryotes that have bona fide mitochondria capable of oxidative phosphorylation. Trypanosomes have unique mitochondrial biology that concerns their mitochondrial metabolism and their unusual mitochondrial morphology that differs to great extent between life stages. Another striking feature is the organization of the mitochondrial genome that does not encode any tRNA genes, thus all tRNAs needed for mitochondrial translation have to be imported. However, the MOM of T. brucei is essentially unchartered territory. It lacks a canonical protein import machinery and facilitation of tRNA translocation remains completely elusive. Using biochemical fractionation and label-free quantitative mass spectrometry for correlated protein abundance-profiling we were able to identify a cluster of 82 candidate proteins that can be localized to the trypanosomal MOM with high confidence. This enabled us to identify a highly unusual, potentially archaic protein import machinery that might also transport tRNAs. Moreover, two-thirds of the identified polypeptides present on the MOM have never been associated with mitochondria before. 40 proteins share homology with proteins of known functions. The function of 42 proteins remains unknown. 11 proteins are essential for the disease-causing bloodstream form of T. brucei and therefore may be exploited as novel drug targets. A comparison with the outer membrane proteome of yeast defines a set of 17 common proteins that are likely present in the MOM of all eukaryotes. Known factors involved in the regulation of mitochondrial morphology are virtually absent in T. brucei. Interestingly, RNAi-mediated ablation of three outer membrane proteins of unknown function resulted in a collapse of the network-like mitochondrion of insect-stage parasites and therefore directly or indirectly are involved in the regulation of mitochondrial morphology.

High colonization rates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Swiss Travellers to South Asia- a prospective observational multicentre cohort study looking at epidemiology, microbiology and risk factors.

BACKGROUND International travel contributes to the worldwide spread of multidrug resistant Gram-negative bacteria. Rates of travel-related faecal colonization with extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae vary for different destinations. Especially travellers returning from the Indian subcontinent show high colonization rates. So far, nothing is known about region-specific risk factors for becoming colonized. METHODS An observational prospective multicentre cohort study investigated travellers to South Asia. Before and after travelling, rectal swabs were screened for third-generation cephalosporin- and carbapenem-resistant Enterobacteriaceae. Participants completed questionnaires to identify risk factors for becoming colonized. Covariates were assessed univariately, followed by a multivariate regression. RESULTS Hundred and seventy persons were enrolled, the largest data set on travellers to the Indian subcontinent so far. The acquired colonization rate with ESBL-producing Escherichia coli overall was 69.4% (95% CI 62.1-75.9%), being highest in travellers returning from India (86.8%; 95% CI 78.5-95.0%) and lowest in travellers returning from Sri Lanka (34.7%; 95% CI 22.9-48.7%). Associated risk factors were travel destination, length of stay, visiting friends and relatives, and eating ice cream and pastry. CONCLUSIONS High colonization rates with ESBL-producing Enterobacteriaceae were found in travellers returning from South Asia. Though risk factors were identified, a more common source, i.e. environmental, appears to better explain the high colonization rates.

Mastitis in dairy heifers: Prevalence and risk factors

Poor udder health represents a serious problem in dairy production and has been investigated intensively, but heifers generally have not been the main focus of mastitis control. The aim of this study was to evaluate the prevalence, risk factors and consequences of heifer mastitis in Switzerland. The study included 166,518 heifers of different breeds (Swiss Red Pied, Swiss Brown Cattle and Holstein). Monthly somatic cell counts (SCCs) provided by the main dairy breeding organisations in Switzerland were monitored for 3 years; the prevalence of subclinical mastitis (SCM) was determined on the basis of SCCs ≥100,000 cells/mL at the first test date. The probability of having SCM at the first test date during lactation was modelled using logistic regression. Analysed factors included data for the genetic background, morphological traits, geographical region, season of parturition and milk composition. The overall prevalence of SCM in heifers during the period from 2006 to 2010 was 20.6%. Higher frequencies of SCM were present in heifers of the Holstein breed (odds ratio, OR, 1.62), heifers with high fat:protein ratios (OR 1.97) and heifers with low milk urea concentrations combined with high milk protein concentrations (OR 3.97). Traits associated with a low risk of SCM were high set udders, high overall breeding values and low milk breeding values. Heifers with SCM on the first test day had a higher risk of either developing chronic mastitis or leaving the herd prematurely.

Periodontal pathogens and associated factors in aggressive periodontitis: results 5-17 years after active periodontal therapy

OBJECTIVES To assess the association between presence of periodontal pathogens and recurrence of disease in patients with aggressive periodontitis (AgP) after active periodontal therapy (APT) and further influencing factors. MATERIAL & METHODS Microbiological samples were taken from 73 patients with AgP 5-17 years after APT at 292 sites (deepest site per quadrant). Real-time polymerase chain reactions were used to detect the periodontal pathogens Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Uni- and multivariate analyses evaluated the associations between pathogens and recurrence of disease, smoking and adjunctive antibiotic therapy. RESULTS At re-examination A. actinomycetemcomitans could be detected in six patients (8.2%), P. gingivalis in 24 (32.9%), T. forsythia in 31 (42.5%) and T. denticola in 35 (48.0%). Increased levels of T. forsythia and T. denticola at re-examination were significantly associated with recurrence of disease in multivariate analyses (OR: 12.72, p < 0.001; OR 5.55, p = 0.002 respectively). Furthermore, high counts of T. denticola were found in patients with increased percentage of sites with clinical attachment levels (CAL) ≥ 6 mm compared to those with low counts (13.8% versus 3.2%, p = 0.005). CONCLUSION In patients with recurrence of disease T. forsythia and T. denticola were detected more frequently and in higher counts. Furthermore, T. denticola was found more frequently in patients with increased CAL.

Incidence of and risk factors for severe hypoglycaemia in treated type 2 diabetes mellitus patients in the UK - a nested case-control analysis

AIMS To assess incidence rates (IRs) of and identify risk factors for incident severe hypoglycaemia in patients with type 2 diabetes newly treated with antidiabetic drugs. METHODS Using the UK-based General Practice Research Database, we performed a retrospective cohort study between 1994 and 2011 and a nested case-control analysis. Ten controls from the population at risk were matched to each case with a recorded severe hypoglycaemia during follow-up on general practice, years of history in the database and calendar time. Using multivariate conditional logistic regression analyses, we adjusted for potential confounders. RESULTS Of 130,761 patients with newly treated type 2 diabetes (mean age 61.7 ± 13.0 years), 690 (0.5%) had an incident episode of severe hypoglycaemia recorded [estimated IR 11.97 (95% confidence interval, CI, 11.11-12.90) per 10,000 person-years (PYs)]. The IR was markedly higher in insulin users [49.64 (95% CI, 44.08-55.89) per 10,000 PYs] than in patients not using insulin [8.03 (95% CI, 7.30-8.84) per 10,000 PYs]. Based on results of the nested case-control analysis increasing age [≥ 75 vs. 20-59 years; adjusted odds ratio (OR), 2.27; 95% CI, 1.65-3.12], cognitive impairment/dementia (adjusted OR, 2.00; 95% CI, 1.37-2.91), renal failure (adjusted OR, 1.34; 95% CI, 1.04-1.71), current use of sulphonylureas (adjusted OR, 4.45; 95% CI, 3.53-5.60) and current insulin use (adjusted OR, 11.83; 95% CI, 9.00-15.54) were all associated with an increased risk of severe hypoglycaemia. CONCLUSIONS Severe hypoglycaemia was recorded in 12 cases per 10,000 PYs. Risk factors for severe hypoglycaemia included increasing age, renal failure, cognitive impairment/dementia, and current use of insulin or sulphonylureas.

Incidence and risk factors for early adjacent vertebral fractures after balloon kyphoplasty for osteoporotic fractures: analysis of the SWISSspine registry

PURPOSE The SWISSspine registry (SSR) was launched in 2005 to assess the safety and effectiveness of balloon kyphoplasty (BKP). In the meantime, repeated reports on high rates of adjacent vertebral fractures (ASF) after BKP of vertebral insufficiency fractures were published. The causes for ASF and their risk factors are still under debate. The purpose of this study was to report the incidence and potential risk factors of ASF within the SSR dataset. METHODS The SSR data points are collected perioperatively and during follow-ups, with surgeon- and patient-based information. All patients documented with a monosegmental osteoporotic vertebral insufficiency fracture between March 2005 and May 2012 were included in the study. The incidence of ASF, significant associations with co-variates (patient age, gender, fracture location, cement volume, preoperative segmental kyphosis, extent of kyphosis correction, and individual co-morbidities) and influence on quality of life (EQ-5D) and back pain (VAS) were analyzed. RESULTS A total of 375 patients with a mean follow-up of 3.6 months was included. ASF were found in 9.9 % (n = 37) and occurred on average 2.8 months postoperatively. Preoperative segmental kyphosis >30° (p = 0.026), and rheumatoid arthritis (p = 0.038) and cardiovascular disease (p = 0.047) were significantly associated with ASF. Furthermore, patients with ASF had significantly higher back pain at the final follow-up (p = 0.001). No further significant associations between the studied co-variates and ASF were seen in the adjusted analysis. CONCLUSIONS The findings suggest that patients with a preoperative segmental kyphosis >30° or patients with co-morbidities like rheumatoid arthritis and a cardiovascular disease are at high risk of ASF within 6 months after the index surgery. In case of an ASF event, back pain levels are significantly increased. LEVEL OF EVIDENCE IV.

Does the (structural) context matter? Analysing individual and structural factors of members’ commitment to sports clubs

Introduction: Over the last decades, Swiss sports clubs have lost their "monopoly" in the market for sports-related services and increasingly are in competition with other sports providers. For many sport clubs long-term membership cannot be seen as a matter of course. Current research on sports clubs in Switzerland – as well as for other European countries – confirms the increasing difficulties in achieving long-term member commitment. Looking at recent findings of the Swiss sport clubs report (Lamprecht, Fischer & Stamm, 2012), it can be noted, that a decrease in memberships does not equally affect all clubs. There are sports clubs – because of their specific situational and structural conditions – that have few problems with member fluctuation, while other clubs show considerable declines in membership. Therefore, a clear understanding of individual and structural factors that trigger and sustain member commitment would help sports clubs to tackle this problem more effectively. This situation poses the question: What are the individual and structural determinants that influence the tendency to continue or to quit the membership? Methods: Existing research has extensively investigated the drivers of members’ commitment at an individual level. As commitment of members usually occurs within an organizational context, the characteristics of the organisation should be also considered. However, this context has been largely neglected in current research. This presentation addresses both the individual characteristics of members and the corresponding structural conditions of sports clubs resulting in a multi-level framework for the investigation of the factors of members’ commitment in sports clubs. The multilevel analysis grant a adequate handling of hierarchically structured data (e.g., Hox, 2002). The influences of both the individual and context level on the stability of memberships are estimated in multi-level models based on a sample of n = 1,434 sport club members from 36 sports clubs. Results: Results of these multi-level analyses indicate that commitment of members is not just an outcome of individual characteristics, such as strong identification with the club, positively perceived communication and cooperation, satisfaction with sports clubs’ offers, or voluntary engagement. It is also influenced by club-specific structural conditions: stable memberships are more probable in rural sports clubs, and in clubs that explicitly support sociability, whereas sporting-success oriented goals in clubs have a destabilizing effect. Discussion/Conclusion: The proposed multi-level framework and the multi-level analysis can open new perspectives for research concerning commitment of members to sports clubs and other topics and problems of sport organisation research, especially in assisting to understand individual behavior within organizational contexts. References: Hox, J. J. (2002). Multilevel analysis: Techniques and applications. Mahwah: Lawrence Erlbaum. Lamprecht, M., Fischer, A., & Stamm, H.-P. (2012). Die Schweizer Sportvereine – Strukturen, Leistungen, Herausforderungen. Zurich: Seismo.

Does context matter? Analysing structural and individual factors of member commitment in sport clubs

This article addresses factors that infl uence member commitment in sport clubs. Based on the theory of social action and the economic behaviour theory, it focuses not only on individual characteristics of club members but also on the corresponding structural conditions of sport clubs. Accordingly, a multilevel framework is developed for explaining member commitment in sport clubs. Different multilevel models were estimated in order to analyse the infl uences of both the individual and corresponding context Level in a sample of n = 1,699 members of 42 Swiss and German sport clubs. The multilevel analysis permitted an adequate handling of hierarchically structured data. Results of These multilevel analyses indicated that the commitment of members is not just an outcome of individual characteristics such as strong identifi cation with their club, positively perceived (collective) solidarity, satisfaction with their sport club, or voluntary engagement. It is also determined by club-specific structural conditions: commitment proves to be more probable in rural sport clubs and clubs that explicitly support sociability. Furthermore, cross-level effects in relation to member commitment were also found between the context variable sociability and the individual variable identification.

Babesia spp. in European wild ruminant species: parasite diversity and risk factors for infection.

Babesia are tick-borne parasites that are increasingly considered as a threat to animal and public health. We aimed to assess the role of European free-ranging wild ruminants as maintenance mammalian hosts for Babesia species and to determine risk factors for infection. EDTA blood was collected from 222 roe deer (Capreolus c. capreolus), 231 red deer (Cervus e. elaphus), 267 Alpine chamois (Rupicapra r. rupicapra) and 264 Alpine ibex (Capra i. ibex) from all over Switzerland and analysed by PCR with pan-Babesia primers targeting the 18S rRNA gene, primers specific for B. capreoli and Babesia sp. EU1, and by sequencing. Babesia species, including B. divergens, B. capreoli, Babesia sp. EU1, Babesia sp. CH1 and B. motasi, were detected in 10.7% of all samples. Five individuals were co-infected with two Babesia species. Infection with specific Babesia varied widely between host species. Cervidae were significantly more infected with Babesia spp. than Caprinae. Babesia capreoli and Babesia sp. EU1 were mostly found in roe deer (prevalences 17.1% and 7.7%, respectively) and B. divergens and Babesia sp. CH1 only in red deer. Factors significantly associated with infection were low altitude and young age. Identification of Babesia sp. CH1 in red deer, co-infection with multiple Babesia species and infection of wild Caprinae with B. motasi and Babesia sp. EU1 are novel findings. We propose wild Caprinae as spillover or accidental hosts for Babesia species but wild Cervidae as mammalian reservoir hosts for B. capreoli, possibly Babesia sp. EU1 and Babesia sp. CH1, whereas their role regarding B. divergens is more elusive.