BackgroundNon-communicable diseases (NCDs) are the largest cause of premature death worldwide. Socioeconomic inequalities contribute to a disparity in the burden of NCDs among disadvantaged and advantaged populations in low (LIC), middle (MIC), and high income countries (HIC). We conducted an overview of systematic reviews to systematically and objectively assess the available evidence on socioeconomic inequalities in relation to morbidity and mortality of NCDs and their risk factors.MethodsWe searched PubMed, The Cochrane Library, EMBASE, SCOPUS, Global Health, and Business Source Complete for relevant systematic reviews published between 2003 and December 2013. Two authors independently screened abstracts and full-text publications and determined the risk of bias of the included systematic reviews.ResultsWe screened 3302 abstracts, 173 full-text publications and ultimately included 22 systematic reviews. Most reviews had major methodological shortcomings; however, our synthesis showed that having low socioeconomic status (SES) and/or living in low and middle income countries (LMIC) increased the risk of developing cardiovascular diseases (CVD), lung and gastric cancer, type 2 diabetes, and chronic obstructive pulmonary disease (COPD). Furthermore, low SES increased the risk of mortality from lung cancer, COPD, and reduced breast cancer survival in HIC. Reviews included here indicated that lower SES is a risk factor for obesity in HIC, but this association varied by SES measure. Early case fatalities of stroke were lower and survival of retinoblastoma was higher in MIC compared to LIC.ConclusionsThe current evidence supports an association between socioeconomic inequalities and NCDs and risk factors for NCDs. However, this evidence is incomplete and limited by the fairly low methodological quality of the systematic reviews, including shortcomings in the study selection and quality assessment process.Electronic supplementary materialThe online version of this article (doi:10.1186/s12889-015-2227-y) contains supplementary material, which is available to authorized users.

The ultrasound scan plays an essential role in the urological-andrological diagnosis. High-resolution transducers (8-15 MHz) make it possible to prove increasingly small changes. The assessment of cystic masses in the testis can also be difficult for experienced doctors. However, a precise diagnosis is crucial for the patient to avoid further invasive diagnostics and therapy. The differential diagnosis of benign intra-testicular cystic lesions include the tubular ectasia of the rete testis (TERT), the cystic dysplasia, epidermoid cysts, dermoid cysts, simple testicular cysts and cysts of the tunica albuginea. Malign testicular tumours with cystic changes are particularly the mature teratoma, carcinomas of the epididymis and metastasis. The following overview shows different sonographic images and interpretations with a particular focus on TERT.

The slow cholinergic transmission in autonomic ganglia is known to be mediated by an inhibition of Kv7 channels via M1 muscarinic acetylcholine receptors. However, in the present experiments using primary cultures of rat superior cervical ganglion neurons, the extent of depolarisation caused by the M1 receptor agonist oxotremorine M did not correlate with the extent of Kv7 channel inhibition in the very same neuron. This observation triggered a search for additional mechanisms. As the activation of M1 receptors leads to a boost in protein kinase C (PKC) activity in sympathetic neurons, various PKC enzymes were inhibited by different means. Interference with classical PKC isoforms led to reductions in depolarisations and in noradrenaline release elicited by oxotremorine M, but left the Kv7 channel inhibition by the muscarinic agonist unchanged. M1 receptor-induced depolarisations were also altered when extra- or intracellular Cl− concentrations were changed, as were depolarising responses to γ-aminobutyric acid. Depolarisations and noradrenaline release triggered by oxotremorine M were reduced by the non-selective Cl− channel blockers 4-acetamido-4′-isothiocyanato-stilbene-2,2′-disulfonic acid and niflumic acid. Oxotremorine M induced slowly rising inward currents at negative membrane potentials that were blocked by inhibitors of Ca2+-activated Cl− and TMEM16A channels and attenuated by PKC inhibitors. These channel blockers also reduced oxotremorine M-evoked noradrenaline release. Together, these results reveal that slow cholinergic excitation of sympathetic neurons involves the activation of classical PKCs and of Ca2+-activated Cl− channels in addition to the well-known inhibition of Kv7 channels.

Background and purpose: M2, M3 and/or M4 muscarinic acetylcholine receptors have been reported to mediate presynaptic inhibition in sympathetic neurons. M1 receptors mediate an inhibition of Kv7, CaV1 and CaV2.2 channels. These effects cause increases and decreases in transmitter release, respectively, but presynaptic M1 receptors are generally considered facilitatory. Here, we searched for inhibitory presynaptic M1 receptors. Experimental approach: In primary cultures of rat superior cervical ganglion neurons, Ca 2+ currents were recorded via the perforated patch-clamp technique, and the release of [ 3 H]-noradrenaline was determined. Key results: The muscarinic agonist oxotremorine M (OxoM) transiently enhanced 3 H outflow and reduced electrically evoked release, once the stimulant effect had faded. The stimulant effect was enhanced by pertussis toxin (PTX) and was abolished by blocking M1 receptors, by opening Kv7 channels and by preventing action potential propagation. The inhibitory effect was not altered by preventing action potentials or by opening Kv7 channels, but was reduced by PTX and w-conotoxin GVIA. The inhibition remaining after PTX treatment was abolished by blockage of M1 receptors or inhibition of phospholipase C. When [ 3 H]-noradrenaline release was triggered independently of voltage-activated Ca 2+ channels (VACCs), OxoM failed to cause any inhibition. The inhibition of Ca 2+ currents by OxoM was also reduced by w-conotoxin and PTX and was abolished by M1 antagonism in PTX-treated neurons. Conclusions and implications:These results demonstrate that M1, in addition to M2, M3 and M4, receptors mediate presynaptic inhibition in sympathetic neurons using phospholipase C to close VACCs.

ObjectiveTo systematically compare the risk of adverse events (AEs) for 13 targeted immunomodulators (TIMs) indicated for ankylosing spondylitis (AS), inflammatory bowel diseases, juvenile idiopathic arthritis, plaque psoriasis, psoriatic arthritis (PsA), or rheumatoid arthritis (RA).MethodsWe searched electronic databases through July 2015 to retrieve randomized controlled trials (RCTs) and observational studies comparing AEs between 2 or more TIMs head‐to‐head. We reported on the following outcomes: number of AEs, discontinuation due to AEs, serious AEs, mortality, serious infections, tuberculosis, herpes zoster, and malignancies. We qualitatively synthesized the literature and conducted random‐effects meta‐analyses if 3 or more studies provided data for an outcome.ResultsTen head‐to‐head RCTs and 51 observational studies were included in this systematic review. A majority of the studies (70%) were conducted in RA patients. Risk of treatment discontinuation due to AEs was higher with infliximab than with adalimumab or etanercept in RA, PsA, and AS. A higher risk for serious infections was noted with infliximab than with abatacept, adalimumab, or etanercept in RA. Risk for treatment discontinuation due to AEs, serious infections, and tuberculosis was lower with etanercept than with adalimumab in RA. Limited evidence suggested no comparative differences in risk for mortality, malignancies, and herpes zoster for adalimumab, etanercept, and infliximab in RA.ConclusionImportant differences were noted in the safety profile of TIMs in RA, generally favoring abatacept, adalimumab, and etanercept over infliximab. Head‐to‐head comparative evidence for other TIMs and non‐RA populations was insufficient to draw conclusions for most of the safety outcomes.

SUMMARYIntroduction: To date, most clinical comparisons of ezetimibe-statin combination therapy versus statin monotherapy have relied entirely on surrogate variables. In this systematic review, we study the efficacy and safety of ezetimibe-statin combination therapy in comparison to statin monotherapy in terms of the prevention of cardiovascular events in hyperlipidemic patients with atherosclerosis and/or diabetes mellitus.

The development of evidence-based guidelines is an interdisciplinary process in which methodologists play an important role. In addition to creating new or assessing existing systematic reviews as a basis for evidence-based decision making, methodologists can support the entire development process. Due to the increasing complexity of methods and the information overload of available publications, cooperation between the involved experts (especially clinicians and methodologists, but also patient representatives) is essential in order to develop reliable, acceptable and practical guidelines. This article looks at eight key points of the guideline development process (transparency, conflicts of interest, composition of guideline development group, establishing evidence foundation, development and formulation of recommendations, external review and updating) from the perspective of methodologists, and highlights problems, challenges and solution approaches. The earliest possible involvement of methodologists, a clear and a--for non-methodologists--understandable presentation of the best available evidence, the integration of methodologists in the creation and formulation of recommendations (systematic, evidence-based decision-making process) and cooperation between the participating experts are essential to improve the development process of evidence-based guidelines.

Of the 5 known subtypes of mAChRs, M 2 , M 3 , and M 4 have been reported to act as inhibitory presynaptic receptors in the nervous system, in general, and in sympathetic neurons, in particular. M 1 receptors, in contrast, have rather been viewed as facilitatory presynaptic receptors. In superior cervical ganglion (SCG) neurons, M 1 receptors are well known to inhibit KCNQ channels. Previously, we were able to show that non-presynaptic M 1 receptors in SCG neurons enhance noradrenaline release through an inhibition of KCNQ channels. However, M 1 receptors also mediate an inhibition of voltage-activated Ca 2+ channels, which represents the predominant mechanism of presynaptic inhibition. Hence, presynaptic M 1 receptors may exert inibitory presynaptic modulation. To test this possibility, we performed experiments on rat superior cervical ganglion neurons. In primary cultures tritium overflow was assayed to investigate the release of [ 3 H]noradrenaline, and the perforated patch-clamp technique was employed to record Ca 2+ currents. The muscarinic agonist oxotremorine M transiently enhanced 3 H outflow and reduced electrically evoked release, once the stimulatory effect had faded. The stimulatory effect was enhanced by pertussis toxin and was abolished by blocking M 1 receptors, by opening KCNQ channels, and by preventing action potential propagation. The inhibitory effect, in contrast, was not altered by preventing action potentials or by opening KCNQ channels, but was reduced by pertussis toxin. The inhibition remaining after pertussis toxin treatment was abolished by blockage of M 1 receptors or inhibition of phospholipase C. When [ 3 H]noradrenaline release was triggered independently of voltage-activated Ca 2+ channels, oxotremorine M failed to cause any inhibition. The inhibition of Ca 2+ currents by oxotremorine M was reduced by pertussis toxin and then abolished by the blockage of M 1 receptors. This demonstrates that M 1 , in addition to M 2 , M 3 , and M 4 , receptors mediate presynaptic inhibition in sympathetic neurons using phospholipase C to close voltage-activated Ca 2+ channels. In addition, our results contradict the widely accepted concept that all inhibitory presynaptic receptors restrict transmitter release through a direct inhibition of Ca 2+ channels via G protein βγ subunits and offer an alternative mechanism.