Analyse der therapeutischen Wirksamkeit von lokaler und systemischer Antibiotikatherapie nach einzeitigem Implantatwechsel bei Osteomyelitis im Ratteninfektmodell

Steigende Raten an komplizierten implantatassoziierten Knocheninfektionen und Erregerresistenzen machen eine intensive und innovative Osteomyelitisforschung notwendig. Wir etablierten mit unserer Arbeit ein valides Ratteninfektmodell, mit dem wir nach einem primären Infektionseingriff mit S.aureus  an der Tibia, kombiniert mit einem Titanimplantat, nach einer Woche fünf verschiedene einzeitige Therapiemethoden umsetzten und in ihrer Wirksamkeit untersuchten. Die erwartete Überlegenheit des Wechsels auf ein PDLLA-10%Gentamicin-Implantat kombiniert mit der system. Gentamicingabe zeigte sich mikrobiologisch nach 35 Tagen in einer Ausheilungsrate von 50%. Die signifikant höchsten Keimzahlen zeigten die Tiere, die lediglich ein unbeschichtetes Titanimplantat erhielten. Die lokale Gentamicintherapie scheint der systemischen Gabe in diesem Stadium überlegen zu sein. Anhand dieses Modelles können in Zukunft weitere antiinfektive oder immunmodulierende Therapieansätze getestet werden

Diabetes is an independent predictor for severe osteoarthritis: Results from a longitudinal cohort study

OBJECTIVE-To evaluate if type 2 diabetes is an independent risk predictor for severe oste-oarthritis (OA). RESEARCH DESIGN AND METHODS-Population-based cohort study with an age-and sex-stratified random sample of 927 men and women aged 40-80 years and followed over 20 years (1990-2010). RESULTS-Rates of arthroplasty (95% CI) were 17.7 (9.4-30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1-6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1-6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1-3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes. CONCLUSIONS-Type 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA.\ua9 2013 by the American Diabetes Association

Phlebotominae (Diptera, Psychodidae) na Província Espeleológica do Vale do Ribeira - 1. Parque Estadual Intervales (PEI), estado de São Paulo, Brasil

The identification of the sandfly fauna and investigation of some ecological aspects of its populations in areas frequented by tourists of the PEI, an Atlantic forest reserve with many caves, were the objective of this study. Captures were undertaken monthly from January 2001 to December 2002, with automatic light traps installed in 13 ecotopes, including caves, forests, domiciliary and peridomiciliary environments, and by aspiration in armadillo burrows. Additionally, although not at regular intervals, Shannon traps were installed in forests and anthropic environments, aspirations were made on cave walls, among roots and fallen leaves, and some insects were captured while biting researchers. A total of 891 sandflies belonging to 21 species were captured. Six hundred specimens representing 19 species were captured with light traps, 215 in anthropic (2.24 insects/trap) and 385 in extra-domiciliary (1.46 insects/trap) environments. Brumptomyia troglodytes was the most abundant species (the Standardised Index of Species Abundance = 0.705). Pintomyia monticola predominated in the Shannon traps and showed anthropophilic and diurnal activity. Psathyromyia pascalei predominated in the aspirations; the largest number being in armadillo burrows. Eleven species were captured in caves; although some might be troglophiles, the majority used these ecotopes as resting places. Nyssomyia intermedia, Nyssomyia neivai and Migonemyia migonei, implicated in the transmission of cutaneous leishmaniasis in the Southeastern Brazilian region, were all found, though in such low densities as to suggest minimal risk of the disease in the PEI.A identificação da fauna flebotomínea e de alguns aspectos ecológicos de suas populações em áreas freqüentadas por turistas no PEI, situado em reserva de mata Atlântica, constituem-se nos objetivos deste estudo. As capturas foram mensais de janeiro/2001 a dezembro/2002, com armadilhas automáticas luminosas em 13 ecótopos, incluindo cavernas, matas e peridomicílio e aspiração em tocas de tatus. Sem intervalos regulares, foram realizadas capturas com armadilhas de Shannon na mata e ambientes antrópicos, aspiração em paredes de cavernas e entre raízes e folhedo e em membros da equipe quando picados por flebotomíneos. No total foram capturados 891 flebotomíneos pertencentes a 21 espécies. Com as armadilhas automáticas luminosas capturou-se 19 espécies e 600 espécimes, 215 em ambiente antrópico (2,24 insetos/armadilha) e 385 em ambiente natural (1,46 insetos/armadilha). Brumptomyia troglodytes foi a mais abundante, com o índice de abundância das espécies padronizado = 0,705. Pintomyia monticola predominou nas armadilhas de Shannon, mostrando-se antropofílica e com atividade hematofágica diurna e noturna. Psathyromyia pascalei predominou nas aspirações, com a maioria dos espécimes aspirados de tocas de tatu. Das 11 espécies capturadas em cavernas, embora algumas possam ser consideradas troglófilas, a maioria usa este ecótopo como local de abrigo. Nyssomyia intermedia, Nyssomyia neivai e Migonemyia migonei, implicados na transmissão da leishmaniose tegumentar na Região Sudeste do Brasil foram capturados, todavia em tão baixa densidade que sugere risco mínimo da doença no PEI.FAPESPIBAMA-S

A polynomial-time algorithm for optimizing over N-fold 4-block decomposable integer programs

In this paper we generalize N-fold integer programs and two-stage integer programs with N scenarios to N-fold 4-block decomposable integer programs. We show that for fixed blocks but variable N, these integer programs are polynomial-time solvable for any linear objective. Moreover, we present a polynomial-time computable optimality certificate for the case of fixed blocks, variable N and any convex separable objective function. We conclude with two sample applications, stochastic integer programs with second-order dominance constraints and stochastic integer multi-commodity flows, which (for fixed blocks) can be solved in polynomial time in the number of scenarios and commodities and in the binary encoding length of the input data. In the proof of our main theorem we combine several non-trivial constructions from the theory of Graver bases. We are confident that our approach paves the way for further extensions

Validation of the German Classification of Diverticular Disease (VADIS)—a prospective bicentric observational study

Purpose: The German Classification of Diverticular Disease was introduced a few years ago. The aim of this study was to determine whether Classification of Diverticular Disease enables an exact stratification of different types of diverticular disease in terms of course and treatment. Methods: This was a prospective, bicentric observational trial. Patients aged ≥ 18 years with diverticular disease were prospectively included. The primary endpoint was the rate of recurrence within 2 year follow-up. Secondary outcome measures were Gastrointestinal Quality of Life Index, Quality of life measured by SF-36, frequency of gastrointestinal complaints, and postoperative complications. Results: A total of 172 patients were included. After conservative management, 40% of patients required surgery for recurrence in type 1b vs. 80% in type 2a/b (p = 0.04). Sixty percent of patients with type 2a (micro-abscess) were in need of surgery for recurrence vs. 100% of patients with type 2b (macro-abscess) (p = 0.11). Patients with type 2a reached 123 ± 15 points in the Gastrointestinal Quality of Life Index compared with 111 ± 14 in type 2b (p = 0.05) and higher scores in the “Mental Component Summary” scale of SF-36 (52 ± 10 vs. 43 ± 13; p = 0.04). Patients with recurrent diverticulitis without complications (type 3b) had less often painful constipation (30% vs. 73%; p = 0.006) when they were operated compared with conservative treatment. Conclusion: Differentiation into type 2a and 2b based on abscess size seems reasonable as patients with type 2b required surgery while patients with type 2a may be treated conservatively. Sigmoid colectomy in patients with type 3b seems to have gastrointestinal complaints during long-term follow-up. Trial registration: https://www.drks.de ID: DRKS0000557

Diabetes is an independent predictor for severe osteoarthritis: Results from a longitudinal cohort study

OBJECTIVE-To evaluate if type 2 diabetes is an independent risk predictor for severe oste-oarthritis (OA). RESEARCH DESIGN AND METHODS-Population-based cohort study with an age-and sex-stratified random sample of 927 men and women aged 40-80 years and followed over 20 years (1990-2010). RESULTS-Rates of arthroplasty (95% CI) were 17.7 (9.4-30.2) per 1,000 person-years in patients with type 2 diabetes and 5.3 (4.1-6.6) per 1,000 person-years in those without (P < 0.001). Type 2 diabetes emerged as an independent risk predictor for arthroplasty: hazard ratios (95% CI), 3.8 (2.1-6.8) (P < 0.001) in an unadjusted analysis and 2.1 (1.1-3.8) (P = 0.023) after adjustment for age, BMI, and other risk factors for OA. The probability of arthroplasty increased with disease duration of type 2 diabetes and applied to men and women, as well as subgroups according to age and BMI. Our findings were corroborated in cross-sectional evaluation by more severe clinical symptoms of OA and structural joint changes in subjects with type 2 diabetes compared with those without type 2 diabetes. CONCLUSIONS-Type 2 diabetes predicts the development of severe OA independent of age and BMI. Our findings strengthen the concept of a strong metabolic component in the pathogenesis of OA.© 2013 by the American Diabetes Association

Does subclinical inflammation contribute to impairment of function of knee joints in aged individuals? High prevalence of ultrasound inflammatory findings

Objectives. To investigate the prevalence of knee US findings of inflammation and structural damage in aged individuals (≥60 years) of a long-term population-based cohort and to correlate these findings with demographic, clinical and laboratory parameters. Methods. Cross-sectional clinical and US investigation of both knee joints during the 2010 follow-up of the prospective population-based Bruneck Study. Demographic variables, physical activity, comorbidities, medications, pain, and functional scales related to the knee joints were recorded. US-assessed parameters were synovial hypertrophy, power Doppler signal, joint effusion, cartilage abnormalities, osteophytes, enthesopathy and bursitis. Statistics included univariate and multivariate regression analysis. Results. A total of 488 subjects (mean age 72.5 years; 53.5% females, 46.5% males) were examined by clinical assessment, and 433 of these underwent US examination of both knees. Both inflammatory and structural abnormalities were found in 296 (68.8%) subjects. Inflammatory abnormalities were significantly associated with age in years, male gender, diabetes and the presence of knee joint symptoms. In the multivariate analysis, age, male gender and knee swelling emerged as independent predictors of inflammation [odds ratio (OR) (95% CI) = 1.06 (1.03, 1.09), 2.55 (1.55, 4.21) and 5.92 (1.99, 17.58), respectively]. Conclusion. The present study showed a high prevalence of US inflammatory abnormalities in the knee joints of a normal aged population. These data suggest a substantial contribution of inflammation in progressive impairment of joint function with age

Adaptive Evolution of the Myo6 Gene in Old World Fruit Bats (Family: Pteropodidae)

PMCID: PMC3631194This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Profinite rigidity for Seifert fibre spaces

An interesting question is whether two 3-manifolds can be distinguished by computing and comparing their collections of finite covers; more precisely, by the profinite completions of their fundamental groups. In this paper, we solve this question completely for closed orientable Seifert fibre spaces. In particular, all Seifert fibre spaces are distinguished from each other by their profinite completions apart from some previously-known examples due to Hempel. We also characterize when bounded Seifert fibre space groups have isomorphic profinite completions, given some conditions on the boundary

A Myo6 Mutation Destroys Coordination between the Myosin Heads, Revealing New Functions of Myosin VI in the Stereocilia of Mammalian Inner Ear Hair Cells

Myosin VI, found in organisms from Caenorhabditis elegans to humans, is essential for auditory and vestibular function in mammals, since genetic mutations lead to hearing impairment and vestibular dysfunction in both humans and mice. Here, we show that a missense mutation in this molecular motor in an ENU-generated mouse model, Tailchaser, disrupts myosin VI function. Structural changes in the Tailchaser hair bundles include mislocalization of the kinocilia and branching of stereocilia. Transfection of GFP-labeled myosin VI into epithelial cells and delivery of endocytic vesicles to the early endosome revealed that the mutant phenotype displays disrupted motor function. The actin-activated ATPase rates measured for the D179Y mutation are decreased, and indicate loss of coordination of the myosin VI heads or ‘gating’ in the dimer form. Proper coordination is required for walking processively along, or anchoring to, actin filaments, and is apparently destroyed by the proximity of the mutation to the nucleotide-binding pocket. This loss of myosin VI function may not allow myosin VI to transport its cargoes appropriately at the base and within the stereocilia, or to anchor the membrane of stereocilia to actin filaments via its cargos, both of which lead to structural changes in the stereocilia of myosin VI–impaired hair cells, and ultimately leading to deafness