Antibiotic resistance and phylogenetic characterization of Acinetobacter baumannii strains isolated from commercial raw meat in Switzerland.

The spread of antibiotic-resistant bacteria through food has become a major public health concern because some important human pathogens may be transferred via the food chain. Acinetobacter baumannii is one of the most life-threatening gram-negative pathogens; multidrug-resistant (MDR) clones of A. baumannii are spreading worldwide, causing outbreaks in hospitals. However, the role of raw meat as a reservoir of A. baumannii remains unexplored. In this study, we describe for the first time the antibiotic susceptibility and fingerprint (repetitive extragenic palindromic PCR [rep-PCR] profile and sequence types [STs]) of A. baumannii strains found in raw meat retailed in Switzerland. Our results indicate that A. baumannii was present in 62 (25.0%) of 248 (CI 95%: 19.7 to 30.9%) meat samples analyzed between November 2012 and May 2013, with those derived from poultry being the most contaminated (48.0% [CI 95%: 37.8 to 58.3%]). Thirty-nine strains were further tested for antibiotic susceptibility and clonality. Strains were frequently not susceptible (intermediate and/or resistant) to third- and fourth-generation cephalosporins for human use (i.e., ceftriaxone [65%], cefotaxime [32%], ceftazidime [5%], and cefepime [2.5%]). Resistance to piperacillin-tazobactam, ciprofloxacin, colistin, and tetracycline was sporadically observed (2.5, 2.5, 5, and 5%, respectively), whereas resistance to carbapenems was not found. The strains were genetically very diverse from each other and belonged to 29 different STs, forming 12 singletons and 6 clonal complexes (CCs), of which 3 were new (CC277, CC360, and CC347). RepPCR analysis further distinguished some strains of the same ST. Moreover, some A. baumannii strains from meat belonged to the clonal complexes CC32 and CC79, similar to the MDR isolates responsible for human infections. In conclusion, our findings suggest that raw meat represents a reservoir of MDR A. baumannii and may serve as a vector for the spread of these pathogens into both community and hospital settings.

Immunologic response to the survivin-derived multi-epitope vaccine EMD640744 in patients with advanced solid tumors

PURPOSE Survivin is a member of the inhibitor-of-apoptosis family. Essential for tumor cell survival and overexpressed in most cancers, survivin is a promising target for anti-cancer immunotherapy. Immunogenicity has been demonstrated in multiple cancers. Nonetheless, few clinical trials have demonstrated survivin-vaccine-induced immune responses. EXPERIMENTAL DESIGN This phase I trial was conducted to test whether vaccine EMD640744, a cocktail of five HLA class I-binding survivin peptides in Montanide(®) ISA 51 VG, promotes anti-survivin T-cell responses in patients with solid cancers. The primary objective was to compare immunologic efficacy of EMD640744 at doses of 30, 100, and 300 μg. Secondary objectives included safety, tolerability, and clinical efficacy. RESULTS In total, 49 patients who received ≥2 EMD640744 injections with available baseline- and ≥1 post-vaccination samples [immunologic-diagnostic (ID)-intention-to-treat] were analyzed by ELISpot- and peptide/MHC-multimer staining, revealing vaccine-activated peptide-specific T-cell responses in 31 patients (63 %). This cohort included the per study protocol relevant ID population for the primary objective, i.e., T-cell responses by ELISpot in 17 weeks following first vaccination, as well as subjects who discontinued the study before week 17 but showed responses to the treatment. No dose-dependent effects were observed. In the majority of patients (61 %), anti-survivin responses were detected only after vaccination, providing evidence for de novo induction. Best overall tumor response was stable disease (28 %). EMD640744 was well tolerated; local injection-site reactions constituted the most frequent adverse event. CONCLUSIONS Vaccination with EMD640744 elicited T-cell responses against survivin peptides in the majority of patients, demonstrating the immunologic efficacy of EMD640744.

Beta-alanine supplementation improves jumping power and affects severe-intensity performance in professional alpine skiers.

INTRODUCTION Supplementation with beta-alanine may have positive effects on severe-intensity, intermittent, and isometric strength-endurance performance. These could be advantageous for competitive alpine skiers, whose races last 45 to 150 s, require metabolic power above the aerobic maximum, and involve isometric muscle work. Further, beta-alanine supplementation affects the muscle force-frequency relationship, which could influence explosiveness. We explored the effects of beta-alanine on explosive jump performance, severe exercise energy metabolism, and severe-intensity ski-like performance. METHODS Nine male elite alpine skiers consumed 4.8 g/d beta-alanine or placebo for 5 weeks in a double-blind fashion. Before and after, they performed countermovement jumps (CMJ), a 90-s cycling bout at 110% VO2max (CLT), and a maximal 90-s box jump test (BJ90). RESULTS Beta-alanine improved maximal (+7 ± 3%, d = 0.9) and mean CMJ power (+7 ± 2%, d = 0.7), tended to reduce oxygen deficit (-3 ± 8%, p = .06) and lactate accumulation (-12 ± 31%) and enhance aerobic energy contribution (+1.3 ± 2.9%, p = .07) in the CLT, and improved performance in the last third of BJ90 (+7 ± 4%, p = .02). These effects were not observed with placebo. CONCLUSIONS Beta-alanine supplementation improved explosive and repeated jump performance in elite alpine skiers. Enhanced muscle contractility could possibly explain improved explosive and repeated jump performance. Increased aerobic energy production could possibly help explain repeated jump performance as well.

De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy.

Epileptic encephalopathies are a phenotypically and genetically heterogeneous group of severe epilepsies accompanied by intellectual disability and other neurodevelopmental features. Using next-generation sequencing, we identified four different de novo mutations in KCNA2, encoding the potassium channel KV1.2, in six isolated patients with epileptic encephalopathy (one mutation recurred three times independently). Four individuals presented with febrile and multiple afebrile, often focal seizure types, multifocal epileptiform discharges strongly activated by sleep, mild to moderate intellectual disability, delayed speech development and sometimes ataxia. Functional studies of the two mutations associated with this phenotype showed almost complete loss of function with a dominant-negative effect. Two further individuals presented with a different and more severe epileptic encephalopathy phenotype. They carried mutations inducing a drastic gain-of-function effect leading to permanently open channels. These results establish KCNA2 as a new gene involved in human neurodevelopmental disorders through two different mechanisms, predicting either hyperexcitability or electrical silencing of KV1.2-expressing neurons.

Scent-marking behaviour and social dynamics in a wild population of Eurasian lynx Lynx lynx.

Scent-marking is widespread among mammals and has been observed in many felid species. Although the behaviour is well-described, little is known about its function in wild felid populations. We investigated patterns of scent-marking and its role in intra- and intersexual communication among resident and non-resident Eurasian lynx Lynx lynx by observing interactions among wild lynx at natural marking sites by means of infrared camera traps. Marking activity of resident animals showed a peak during the mating season and was lowest during the time when females gave birth and lactated. Both sexes scent-marked, but male lynx visited marking sites much more often than females and marked relatively more often when visiting a site. Most visits to marking sites were by residents but we also observed scent-marking by non-residents. Juveniles were never observed marking. We found no evidence of lynx regularly renewing scent-marks after a certain 'expiry date' but the presence of a strange scent-mark triggered over-marking. Males responded similarly to the presence of another individual's scent-mark, irrespective of whether it was the top- or the underlying scent-mark in a mixture of scent-marks they encountered. Our results suggest that marking sites could serve as 'chemical bulletin boards', where male lynx advertise their presence and gain information on ownership relationships in a given area. Females placed their urine marks on top of the ones left by resident males, but further studies are needed to explain the functions of over-marking in females.

Copeptin Is Associated with Kidney Length, Renal Function, and Prevalence of Simple Cysts in a Population-Based Study.

Arginine vasopressin (AVP) has a key role in osmoregulation by facilitating water transport in the collecting duct. Recent evidence suggests that AVP may have additional effects on renal function and favor cyst growth in polycystic kidney disease. Whether AVP also affects kidney structure in the general population is unknown. We analyzed the association of copeptin, an established surrogate for AVP, with parameters of renal function and morphology in a multicentric population-based cohort. Participants from families of European ancestry were randomly selected in three Swiss cities. We used linear multilevel regression analysis to explore the association of copeptin with renal function parameters as well as kidney length and the presence of simple renal cysts assessed by ultrasound examination. Copeptin levels were log-transformed. The 529 women and 481 men had median copeptin levels of 3.0 and 5.2 pmol/L, respectively (P<0.001). In multivariable analyses, the copeptin level was associated inversely with eGFR (β=-2.1; 95% confidence interval [95% CI], -3.3 to -0.8; P=0.002) and kidney length (β=-1.2; 95% CI, -1.9 to -0.4; P=0.003) but positively with 24-hour urinary albumin excretion (β=0.11; 95% CI, 0.01 to 0.20; P=0.03) and urine osmolality (β=0.08; 95% CI, 0.05 to 0.10; P<0.001). A positive association was found between the copeptin level and the presence of renal cysts (odds ratio, 1.6; 95% CI, 1.1 to 2.4; P=0.02). These results suggest that AVP has a pleiotropic role in renal function and may favor the development of simple renal cysts.

Associations of ambulatory blood pressure with urinary caffeine and caffeine metabolite excretions.

Intake of caffeinated beverages might be associated with reduced cardiovascular mortality possibly via the lowering of blood pressure. We estimated the association of ambulatory blood pressure with urinary caffeine and caffeine metabolites in a population-based sample. Families were randomly selected from the general population of Swiss cities. Ambulatory blood pressure monitoring was conducted using validated devices. Urinary caffeine, paraxanthine, theophylline, and theobromine excretions were measured in 24 hours urine using ultrahigh performance liquid chromatography tandem mass spectrometry. We used mixed models to explore the associations of urinary excretions with blood pressure although adjusting for major confounders. The 836 participants (48.9% men) included in this analysis had mean age of 47.8 and mean 24-hour systolic and diastolic blood pressure of 120.1 and 78.0 mm Hg. For each doubling of caffeine excretion, 24-hour and night-time systolic blood pressure decreased by 0.642 and 1.107 mm Hg (both P values <0.040). Similar inverse associations were observed for paraxanthine and theophylline. Adjusted night-time systolic blood pressure in the first (lowest), second, third, and fourth (highest) quartile of paraxanthine urinary excretions were 110.3, 107.3, 107.3, and 105.1 mm Hg, respectively (P trend <0.05). No associations of urinary excretions with diastolic blood pressure were generally found, and theobromine excretion was not associated with blood pressure. Anti-hypertensive therapy, diabetes mellitus, and alcohol consumption modify the association of caffeine urinary excretion with systolic blood pressure. Ambulatory systolic blood pressure was inversely associated with urinary excretions of caffeine and other caffeine metabolites. Our results are compatible with a potential protective effect of caffeine on blood pressure.

IgA-Nephropathie und Purpura Schönlein-Henoch - ein breites Spektrum

IgA nephropathy is the most common glomerulonephritis in Europe. The disease has been discovered in 1968 in Paris by Jean Berger at the Necker-Children's Hospital. Diagnosis is made by kidney biopsy and requires the presence of mesangial deposits of IgA. This form of glomerulonephritis can be seen in children and adults. In childhood, it most frequently presents within the context of Schoenlein-Henoch purpura. In adulthood, the most common form is limited to the kidney. Schoenlein-Henoch purpura can be seen in adults and manifests as a very aggressive vasculitis, usually in the context of a specific drug intake. The underlying pathophysiological concept today is an insufficient glycosylation of the IgA1 hinge region triggering the formation of autoantibodies against this site. Therapeutic options for the disease are limited. Important is optimal blood pressure control. Selected patients will profit from steroid therapy.

Oxygen consumption while standing iwth and unstable shoe design

This study explored the effects of unstable shoe design on oxygen consumption. Methods. Oxygen consumption (VO2) and heart rate (HR) were measured in 16 individuals while barefoot, wearing unstable shoes (Masai Barefoot Technology) and wearing conventional sport shoes while standing and walking on a treadmill and for 5 individuals while walking around a 400 m track. Results. When wearing the MBT shoes, a significant (p < 0.01) increase of 9.3 ± 5.2% in VO2 was measured while standing quietly for 6 min. No differences in VO2 and HR were observed between the MBT shoes or weight-adjusted conventional shoes (to match the weight of the MBT shoes) while walking on a treadmill. However, significant increases (p < 0.01) in VO2 (4.4 ± 8.2%) and HR (3.6 ± 7.3%) were observed for the MBT shoes compared with being barefoot. No significant differences in VO2 and HR were recorded while walking around a 400 m track either with MBT shoes, weight-adjusted conventional shoes or barefoot. Nonetheless, a comparison of the MBT shoes with barefoot revealed a tendency for VO2 to be higher when wearing the MBT shoes (7.1 ± 6.5%, p < 0.1) although HR was not significantly affected. Conclusions. The unstable shoe design predominantly effects oxygen consumption while standing, most likely due to increased muscle activity of the lower extremities.

Determination of respiratory gas flow by electrical impedance tomography in an animal model of mechanical ventilation

Background A recent method determines regional gas flow of the lung by electrical impedance tomography (EIT). The aim of this study is to show the applicability of this method in a porcine model of mechanical ventilation in healthy and diseased lungs. Our primary hypothesis is that global gas flow measured by EIT can be correlated with spirometry. Our secondary hypothesis is that regional analysis of respiratory gas flow delivers physiologically meaningful results. Methods In two sets of experiments n = 7 healthy pigs and n = 6 pigs before and after induction of lavage lung injury were investigated. EIT of the lung and spirometry were registered synchronously during ongoing mechanical ventilation. In-vivo aeration of the lung was analysed in four regions-of-interest (ROI) by EIT: 1) global, 2) ventral (non-dependent), 3) middle and 4) dorsal (dependent) ROI. Respiratory gas flow was calculated by the first derivative of the regional aeration curve. Four phases of the respiratory cycle were discriminated. They delivered peak and late inspiratory and expiratory gas flow (PIF, LIF, PEF, LEF) characterizing early or late inspiration or expiration. Results Linear regression analysis of EIT and spirometry in healthy pigs revealed a very good correlation measuring peak flow and a good correlation detecting late flow. PIFEIT = 0.702 · PIFspiro + 117.4, r2 = 0.809; PEFEIT = 0.690 · PEFspiro-124.2, r2 = 0.760; LIFEIT = 0.909 · LIFspiro + 27.32, r2 = 0.572 and LEFEIT = 0.858 · LEFspiro-10.94, r2 = 0.647. EIT derived absolute gas flow was generally smaller than data from spirometry. Regional gas flow was distributed heterogeneously during different phases of the respiratory cycle. But, the regional distribution of gas flow stayed stable during different ventilator settings. Moderate lung injury changed the regional pattern of gas flow. Conclusions We conclude that the presented method is able to determine global respiratory gas flow of the lung in different phases of the respiratory cycle. Additionally, it delivers meaningful insight into regional pulmonary characteristics, i.e. the regional ability of the lung to take up and to release air.