Spinning around or stagnation - what do osteoblasts and chondroblasts really like?

<p>Abstract</p> <p>Objective</p> <p>The influcence of cytomechanical forces in cellular migration, proliferation and differentation of mesenchymal stem cells (MSCs) is still poorly understood in detail.</p> <p>Methods</p> <p>Human MSCs were isolated and cultivated onto the surface of a 3 × 3 mm porcine collagen I/III carrier. After incubation, cell cultures were transfered to the different cutures systems: regular static tissue flasks (group I), spinner flasks (group II) and rotating wall vessels (group III). Following standard protocols cells were stimulated lineage specific towards the osteogenic and chondrogenic lines. To evaluate the effects of applied cytomechanical forces towards cellular differentiation distinct parameters were measured (morphology, antigen and antigen expression) after a total cultivation period of 21 days in vitro.</p> <p>Results</p> <p>Depending on the cultivation technique we found significant differences in both gen and protein expression.</p> <p>Conclusion</p> <p>Cytomechanical forces with rotational components strongly influence the osteogenic and chondrogenic differentiation.</p

An Adaptive Chlamydia trachomatis-Specific IFN-γ-Producing CD4+ T Cell Response Is Associated With Protection Against Chlamydia Reinfection in Women

Background: Adaptive immune responses that mediate protection against Chlamydia trachomatis (CT) remain poorly defined in humans. Animal chlamydia models have demonstrated that CD4+ Th1 cytokine responses mediate protective immunity against reinfection. To better understand protective immunity to CT in humans, we investigated whether select CT-specific CD4+ Th1 and CD8+ T cell cytokine responses were associated with protection against CT reinfection in women. Methods: Peripheral blood mononuclear cells were collected from 135 CT-infected women at treatment and follow-up visits and stimulated with CT antigens. CD4+ and CD8+ T-cells expressing IFN-γ, TNF-α, and/or IL-2 were assessed using intracellular cytokine staining and cytokine responses were compared between visits and between women with vs. without CT reinfection at follow-up. Results: A CD4+TNF-α response was detected in the majority (77%) of study participants at the treatment visit, but a lower proportion had this response at follow-up (62%). CD4+ IFN-γ and CD4+ IL-2 responses occurred less frequently at the treatment visit (32 and 18%, respectively), but increased at follow-up (51 and 41%, respectively). CD8+ IFN-γ and CD8+ TNF-α responses were detected more often at follow-up (59% for both responses) compared to the treatment visit (30% for both responses). At follow-up, a CD4+IFN-γ response was detected more often in women without vs. with reinfection (60 vs. 33%, P = 0.005). Conclusions: Our findings suggest that a CT-specific CD4+ IFN-γ response is associated with protective immunity against CT reinfection and is thus an important component of adaptive immunity to CT in women

Graphical genotyping as a method to map Ny ((o,n)sto) and Gpa5 using a reference panel of tetraploid potato cultivars

The method of graphical genotyping is applied to a panel of tetraploid potato cultivars to visualize haplotype sharing. The method allowed to map genes involved in virus and nematode resistance. The physical coordinates of the amount of linkage drag surrounding these genes are easily interpretable. Graphical genotyping is a visually attractive and easily interpretable method to represent genetic marker data. In this paper, the method is extended from diploids to a panel of tetraploid potato cultivars. Application of filters to select a subset of SNPs allows one to visualize haplotype sharing between individuals that also share a specific locus. The method is illustrated with cultivars resistant to Potato virus Y (PVY), while simultaneously selecting for the absence of the SNPs in susceptible clones. SNP data will then merge into an image which displays the coordinates of a distal genomic region on the northern arm of chromosome 11 where a specific haplotype is introgressed from the wild potato species S. stoloniferum (CPC 2093) carrying a gene (Ny ((o,n)sto) ) conferring resistance to two PVY strains, PVYO and PVYNTN. Graphical genotyping was also successful in showing the haplotypes on chromosome 12 carrying Ry-f (sto) , another resistance gene derived from S. stoloniferum conferring broad-spectrum resistance to PVY, as well as chromosome 5 haplotypes from S. vernei, with the Gpa5 locus involved in resistance against Globodera pallida cyst nematodes. The image also shows shortening of linkage drag by meiotic recombination of the introgression segment in more recent breeding material. Identity-by-descent was found to be a requirement for using graphical genotyping, which is proposed as a non-statistical alternative method for gene discovery, as compared with genome-wide association studies. The potential and limitations of the method are discussed.Peer reviewe

Home Screening for Bacterial Vaginosis to Prevent Sexually Transmitted Diseases

Background. Longitudinal studies have consistently found a significant association between bacterial vaginosis (BV) and acquisition of sexually transmitted diseases. However, there are limited prospective data to confirm these findings

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Chlamydia trachomatis, Mycoplasma genitalium, and Trichomonas vaginalis Infections in Men With Nongonococcal Urethritis: Predictors and Persistence After Therapy

Background. Chlamydia trachomatis (CT), Mycoplasma genitalium (MG), and Trichomonas vaginalis (TV) are sexually transmitted infections (STIs) associated with nongonococcal urethritis (NGU). We assessed their predictors and persistence after treatment

Scaling Dynamic Response and Destructive Metabolism in an Immunosurveillant Anti-Tumor System Modulated by Different External Periodic Interventions

On the basis of two universal power-law scaling laws, i.e. the scaling dynamic hysteresis in physics and the allometric scaling metabolism in biosystem, we studied the dynamic response and the evolution of an immunosurveillant anti-tumor system subjected to a periodic external intervention, which is equivalent to the scheme of a radiotherapy or chemotherapy, within the framework of the growth dynamics of tumor. Under the modulation of either an abrupt or a gradual change external intervention, the population density of tumors exhibits a dynamic hysteresis to the intervention. The area of dynamic hysteresis loop characterizes a sort of dissipative-therapeutic relationship of the dynamic responding of treated tumors with the dose consumption of accumulated external intervention per cycle of therapy. Scaling the area of dynamic hysteresis loops against the intensity of an external intervention, we deduced a characteristic quantity which was defined as the theoretical therapeutic effectiveness of treated tumor and related with the destructive metabolism of tumor under treatment. The calculated dose-effectiveness profiles, namely the dose cumulant per cycle of intervention versus the therapeutic effectiveness, could be well scaled into a universal quadratic formula regardless of either an abrupt or a gradual change intervention involved. We present a new concept, i.e., the therapy-effect matrix and the dose cumulant matrix, to expound the new finding observed in the growth and regression dynamics of a modulated anti-tumor system

Updated European Consensus Statement on diagnosis and treatment of adult ADHD

Background Attention-deficit/hyperactivity disorder (ADHD) is among the most common psychiatric disorders of childhood that often persists into adulthood and old age. Yet ADHD is currently underdiagnosed and undertreated in many European countries, leading to chronicity of symptoms and impairment, due to lack of, or ineffective treatment, and higher costs of illness. Methods The European Network Adult ADHD and the Section for Neurodevelopmental Disorders Across the Lifespan (NDAL) of the European Psychiatric Association (EPA), aim to increase awareness and knowledge of adult ADHD in and outside Europe. This Updated European Consensus Statement aims to support clinicians with research evidence and clinical experience from 63 experts of European and other countries in which ADHD in adults is recognized and treated. Results Besides reviewing the latest research on prevalence, persistence, genetics and neurobiology of ADHD, three major questions are addressed: (1) What is the clinical picture of ADHD in adults? (2) How should ADHD be properly diagnosed in adults? (3) How should adult ADHDbe effectively treated? Conclusions ADHD often presents as a lifelong impairing condition. The stigma surrounding ADHD, mainly due to lack of knowledge, increases the suffering of patients. Education on the lifespan perspective, diagnostic assessment, and treatment of ADHD must increase for students of general and mental health, and for psychiatry professionals. Instruments for screening and diagnosis of ADHD in adults are available, as are effective evidence-based treatments for ADHD and its negative outcomes. More research is needed on gender differences, and in older adults with ADHD. (c) 2018 The Author(s). Published by Elsevier Masson SAS.Peer reviewe

Modeling double strand break susceptibility to interrogate structural variation in cancer

Abstract Background Structural variants (SVs) are known to play important roles in a variety of cancers, but their origins and functional consequences are still poorly understood. Many SVs are thought to emerge from errors in the repair processes following DNA double strand breaks (DSBs). Results We used experimentally quantified DSB frequencies in cell lines with matched chromatin and sequence features to derive the first quantitative genome-wide models of DSB susceptibility. These models are accurate and provide novel insights into the mutational mechanisms generating DSBs. Models trained in one cell type can be successfully applied to others, but a substantial proportion of DSBs appear to reflect cell type-specific processes. Using model predictions as a proxy for susceptibility to DSBs in tumors, many SV-enriched regions appear to be poorly explained by selectively neutral mutational bias alone. A substantial number of these regions show unexpectedly high SV breakpoint frequencies given their predicted susceptibility to mutation and are therefore credible targets of positive selection in tumors. These putatively positively selected SV hotspots are enriched for genes previously shown to be oncogenic. In contrast, several hundred regions across the genome show unexpectedly low levels of SVs, given their relatively high susceptibility to mutation. These novel coldspot regions appear to be subject to purifying selection in tumors and are enriched for active promoters and enhancers. Conclusions We conclude that models of DSB susceptibility offer a rigorous approach to the inference of SVs putatively subject to selection in tumors

Prevalence of pulmonary embolism among patients hospitalized for syncope

BACKGROUNDThe prevalence of pulmonary embolism among patients hospitalized for syncope is not well documented, and current guidelines pay little attention to a diagnostic workup for pulmonary embolism in these patients.METHODSWe performed a systematic workup for pulmonary embolism in patients admitted to 11 hospitals in Italy for a first episode of syncope, regardless of whether there were alternative explanations for the syncope. The diagnosis of pulmonary embolism was ruled out in patients who had a low pretest clinical probability, which was defined according to the Wells score, in combination with a negative D-dimer assay. In all other patients, computed tomographic pulmonary angiography or ventilation-perfusion lung scanning was performed.RESULTSA total of 560 patients (mean age, 76 years) were included in the study. A diagnosis of pulmonary embolism was ruled out in 330 of the 560 patients (58.9%) on the basis of the combination of a low pretest clinical probability of pulmonary embolism and negative D- dimer assay. Among the remaining 230 patients, pulmonary embolism was identified in 97 (42.2%). In the entire cohort, the prevalence of pulmonary embolism was 17.3% (95% confidence interval, 14.2 to 20.5). Evidence of an embolus in a main pulmonary or lobar artery or evidence of perfusion defects larger than 25% of the total area of both lungs was found in 61 patients. Pulmonary embolism was identified in 45 of the 355 patients (12.7%) who had an alternative explanation for syncope and in 52 of the 205 patients (25.4%) who did not.CONCLUSIONSPulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope