Increased body fat is independently and negatively related with cardiorespiratory fitness levels in children and adolescents with normal weight.

Body mass index (BMI) is related with cardiorespiratory fitness (CRF), but less is known regarding the combined relationships between BMI and body fat (BF) on CRF. Cross-sectional study included 2361 girls and 2328 boys aged 10–18 years living in the area of Lisbon, Portugal. BMI was calculated by measuring height and weight, and obesity was assessed by international criteria. BF was assessed by bioimpedance. CRF was assessed by the 20-m shuttle run and the participants were classified as normal-to-high or low-CRF level according to Fitness gram criterion-referenced standards. The prevalence of low CRF was 47 and 39% in girls and boys, respectively. The corresponding values for the prevalence of obesity were 4.8 and 5.6% (not significant) and of excess BF of 12.1 and 25.1% (P <0.001), respectively. In both sexes, BMI and BF were inversely related with CRF: r = – 0.53 and – 0.45 for BMI and % BF, respectively, in boys and the corresponding values in girls were – 0.50 and – 0.33 (all P <0.01). When compared with a participant with normal BMI and BF, the odds ratios (95% confidence interval) for low CRF were 1.94 (1.46–2.58) for a participant with normal BMI and high BF, and 6.19 (5.02–7.63) for a participant with high BMI and high BF. The prevalence of low-CRF levels is high in Portuguese youths. BF negatively influences CRF levels among children/adolescents with normal BMI.

La probabilidad de supervivencia en un modelo con reaseguro proporcional de umbral

[spa] En este artículo presentamos una nueva estrategia de reaseguro, a la que denominamos estrategia de reaseguro umbral, que actúa de forma diferente en función del nivel de las reservas. Así, para unos niveles de las reservas inferiores a un determinado nivel, el gestor decide aplicar un reaseguro proporcional, y para niveles superiores, al considerar que se ha alcanzado cierta solvencia en la cartera, opta por no ceder ningún porcentaje del riesgo. El análisis del efecto de la introducción del reaseguro umbral sobre la probabilidad de supervivencia, y su comparación con el reaseguro proporcional y la opción de no reasegurar, nos permite hallar estrategias de reaseguro equivalentes desde el punto de vista de la solvencia. Palabras clave: teoría del riesgo, reaseguro de umbral, reaseguro proporcional, probabilidad de supervivencia.

Indications à la coronarographie en urgence. Partie II: syndromes coronariens aigus sans élévation du segment ST [Indications for urgent coronary angiography. Part II: Acute coronary syndromes without ST-segment elevation]

The optimal treatment strategy for patients presenting with an acute coronary syndrome without ST elevation is controversial and different therapeutic approaches are recognized. Currently, given the literature available, it is not possible to recommend a universal systematic invasive approach. It is essential to individually risk stratify patients in order to identify those high risk patients that have been shown to benefit from an invasive strategy. Compared to conservative medical treatment, patients at low risk have not been shown to benefit from an invasive strategy. Urgent coronary angiography remains recommended for those patients with persistent or recurrent ischemic symptoms under optimal medical treatment.

CD10 is inversely associated with nuclear factor-kappa B and predicts biochemical recurrence after radical prostatectomy.

INTRODUCTION: The cell surface endopeptidase CD10 (neutral endopeptidase) and nuclear factor-&#954;B (NF-&#954;B) have been independently associated with prostate cancer (PC) progression. We investigated the correlations between these two factors and their prognostic relevance in terms of biochemical (prostate-specific antigen, PSA) relapse after radical prostatectomy (RP) for localized PC. PATIENTS AND METHODS: The immunohistochemical expression of CD10 and NF-&#954;B in samples from 70 patients who underwent RP for localized PC was correlated with the preoperative PSA level, Gleason score, pathological stage and time to PSA failure. RESULTS: CD10 expression was inversely associated with NF-&#954;B expression (p < 0.001), stage (p = 0.03) and grade (p = 0.003), whereas NF-&#954;B was directly related with stage (p = 0.006) and grade (p = 0.002). The median time to PSA failure was 56 months. CD10 and NF-&#954;B were directly (p < 0.001) and inversely (p < 0.001) correlated with biochemical recurrence-free survival, respectively. CD10 expression (p = 0.022) and stage (p = 0.018) were independently associated with time to biochemical recurrence. CONCLUSION: Low CD10 expression is an adverse prognostic factor for biochemical relapse after RP in localized PC, which is also associated with high NF-&#954;B expression. Decreased CD10 expression which would lead to increased neuropeptide signaling and NF-&#954;B activity may be present in a subset of early PCs.

High prevalence of severe vitamin D deficiency in combined antiretroviral therapy-naive and successfully treated Swiss HIV patients.

OBJECTIVES: To evaluate the prevalence of 25-hydroxyvitamin D [25(OH)D] deficiency in HIV-positive patients, a population at risk for osteoporosis. DESIGN: Retrospective assessment of vitamin D levels by season and initiation of combined antiretroviral therapy (cART). METHODS: 25(OH)D was measured in 211 HIV-positive patients: samples were taken before initiation of cART from February to April or from August to October as well as 12 (same season) and 18 months (alternate season) after starting cART. 1,25-Dihydroxyvitamin D [1,25(OH)2D] was measured in a subset of 74 patients. Multivariable analyses included season, sex, age, ethnicity, BMI, intravenous drug use (IDU), renal function, time since HIV diagnosis, previous AIDS, CD4 cell count and cART, in particular nonnucleoside reverse transcriptase inhibitor (NNRTI) and tenofovir (TDF) use. RESULTS: At baseline, median 25(OH)D levels were 37 (interquartile range 20-49) nmol/l in spring and 57 (39-74) nmol/l in the fall; 25(OH)D deficiency less than 30 nmol/l was more prevalent in spring (42%) than in fall (14%), but remained unchanged regardless of cART exposure. In multivariable analysis, 25(OH)D levels were higher in white patients and those with a longer time since HIV diagnosis and lower in springtime measurements and in those with active IDU and NNRTI use. 1-Hydroxylation rates were significantly higher in patients with low 25(OH)D. Hepatitis C seropositivity, previous AIDS and higher CD4 cell counts correlated with lower 1,25(OH)2D levels, whereas BMI and TDF use were associated with higher levels. In TDF-treated patients, higher 1,25(OH)2D correlated with increases in serum alkaline phosphatase. CONCLUSION: Based on the high rate of vitamin D deficiency in HIV-positive patients, systematic screening with consideration of seasonality is warranted. The impact of NNRTIs on 25(OH)D and TDF on 1,25(OH)2D needs further attention.

Fibrin sealant for fasciocutaneous flaps.

Fibrin sealant is used in many areas of surgery. We present a novel aspect of flap insetting in the ischial region using fibrin spray to seal the transferred tissue. We analyzed 10 patients suffering from decubital ulcers and assessed drainage output, time of drain removal, as well as complications following fasciocutaneous flap surgery. Patients were randomized to receive sprayed fibrin glue (study group) or not (control group) before wound closure. The mean drainage time was 4 +/- 1 days in the study group and 6 +/- 1 days in the control group ( P = 0.06). The mean drainage volume was 100 +/- 20 mL in the study group and 168 +/- 30 mL in the control group ( P &lt; 0.01). Fibrin sealant led to reduced drainage volumes and duration of drainage, indicating a beneficial effect of the application of fibrin glue in fasciocutaneous flap surgery for pressure sore coverage.

International consensus guidelines on the management of cytomegalovirus in solid organ transplantation.

Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.

Putative adverse outcome pathways relevant to neurotoxicity.

The Adverse Outcome Pathway (AOP) framework provides a template that facilitates understanding of complex biological systems and the pathways of toxicity that result in adverse outcomes (AOs). The AOP starts with an molecular initiating event (MIE) in which a chemical interacts with a biological target(s), followed by a sequential series of KEs, which are cellular, anatomical, and/or functional changes in biological processes, that ultimately result in an AO manifest in individual organisms and populations. It has been developed as a tool for a knowledge-based safety assessment that relies on understanding mechanisms of toxicity, rather than simply observing its adverse outcome. A large number of cellular and molecular processes are known to be crucial to proper development and function of the central (CNS) and peripheral nervous systems (PNS). However, there are relatively few examples of well-documented pathways that include causally linked MIEs and KEs that result in adverse outcomes in the CNS or PNS. As a first step in applying the AOP framework to adverse health outcomes associated with exposure to exogenous neurotoxic substances, the EU Reference Laboratory for Alternatives to Animal Testing (EURL ECVAM) organized a workshop (March 2013, Ispra, Italy) to identify potential AOPs relevant to neurotoxic and developmental neurotoxic outcomes. Although the AOPs outlined during the workshop are not fully described, they could serve as a basis for further, more detailed AOP development and evaluation that could be useful to support human health risk assessment in a variety of ways.

Cost effectiveness and cost utility of risedronate for osteoporosis treatment and fracture prevention in women: a Swiss perspective.

OBJECTIVES: To assess the incremental cost-effectiveness ratio (ICER) and incremental cost-utility ratio (ICUR) of risedronate compared to no intervention in postmenopausal osteoporotic women in a Swiss perspective. METHODS: A previously validated Markov model was populated with epidemiological and cost data specific to Switzerland and published utility values, and run on a population of 1,000 women of 70 years with established osteoporosis and previous vertebral fracture, treated over 5 years with risedronate 35 mg weekly or no intervention (base case), and five cohorts (according to age at therapy start) with eight risk factor distributions and three lengths of residual effects. RESULTS: In the base case population, the ICER of averting a hip fracture and the ICUR per quality-adjusted life year gained were both dominant. In the presence of a previous vertebral fracture, the ICUR was below euro45,000 (pound30,000) in all the scenarios. For all osteoporotic women&gt;or=70 years of age with at least one risk factor, the ICUR was below euro45,000 or the intervention may even be cost saving. Age at the start of therapy and the fracture risk profile had a significant impact on results. CONCLUSION: Assuming a 2-year residual effect, that ICUR of risedronate in women with postmenopausal osteoporosis is below accepted thresholds from the age of 65 and even cost saving above the age of 70 with at least one risk factor.

State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs--liver, lung, skin, brain--are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.

Transolecranon anterior fracture dislocation.

Between January 1996 and July 2003, 93 consecutive patients operated on with a diagnosis of olecranon fractures were identified from our trauma unit files. Fourteen transolecranon fracture-dislocations were found after a retrospective X-radiographic evaluation. Eight patients were women and six were men, with a mean age of 54 years. There were 4 noncomminuted olecranon fractures, treated with K-wires and single tension-band wiring. The remaining 10 fractures were complex fractures, treated in 3 cases with multiple K-wires and single tension-band wiring, in 2 by use of one-third tubular plates, in 1 with a 3.5-mm dynamic compression plate, and in the remaining 4 with 3.5-mm reconstruction plates. Ligament repair was not performed in any case. Three patients needed reoperation because of early failure of primary fixation. Patients were reviewed at a mean follow-up of 3.6 years. Two reported difficulties in daily activities, none with any symptoms of elbow instability. According to the Broberg and Morrey score, 4 patients had excellent results, 6 had good results, 2 had fair results, and 2 had poor results. Four patients showed signs of degenerative arthritis on the radiographs obtained at follow-up. We conclude that transolecranon fracture-dislocation is an underreported and misdiagnosed injury. Various fixation techniques can restore the anatomic relationships and contour of the trochlear notch; the imperative goal is to obtain a good stable primary fixation and allow early active mobilization.