Androgen deprivation and SARS-CoV-2 in men with prostate cancer

Non peer reviewe

P2P Media Streaming with HTML5 and WebRTC

Abstract-Video-on-demand (VoD) services, such as YouTube, generate most of the Internet traffic today, and the popularity of video services is growing. Service and CDN providers have to invest more and more in distribution networks, which creates pressure to innovate novel approaches. Peer-to-peer (P2P) streaming is a viable alternative that is scalable and can meet the increasing demand. The emerging HTML5 standard introduces APIs that give web browsers an ability to communicate directly with each other in real time. New standards also enable a setup, where browsers can act as P2P nodes. This paper reviews whether the new HTML5 and WebRTC standards are a fit for P2P video streaming, evaluates the performance challenges and proposes solutions. Preliminary analysis indicates that HTML5 can be applied to VoD, but there are concerns

Effects of frequent and long-term exercise on neuropsychiatric symptoms in patients with Alzheimer's disease - Secondary analyses of a randomized, controlled trial (FINALEX)

Background: Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD) and are associated with admission to institutional care. Current guidelines recommend non-pharmacological interventions as the first-line treatment for NPS. However, high-quality randomized studies focused on NPS are scarce. The objective here was to examine whether a regular and long-term exercise programme either at home or as a group-based exercise at an adult day care centre has beneficial effects on AD patients' NPS or permanent institutionalizations. Design, setting, and participants: A randomized, controlled trial with 210 community-dwelling AD patients. Intervention: Two types of intervention comprising (1) group-based exercise in day care centres (GE) and (2) tailored home-based exercise (HE), both twice a week for 12 months, were compared with (3) a control group (CG) receiving usual community care. Measurements: NPS were measured with the Neuropsychiatric Inventory (NPI) at baseline and 6 months, and depression with the Cornell Scale for Depression in Dementia (CSDD) at baseline and 12 months. Data on institutionalizations were retrieved from central registers. Results: No significant differences between the groups were detected in NPI at 6 months or in CSDD at 12 months when analyses were adjusted for age, sex, baseline Clinical Dementia Rating, and Functional Independence Measure. There was no difference in admissions to permanent institutional care between the groups. Conclusions: Regular, long-term exercise intervention did not decrease NPS in patients with AD. (C) 2017 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.Peer reviewe

Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism

Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder characterized by infertility and the absence of puberty. Defects in GnRH neuron migration or altered GnRH secretion and/or action lead to a severe gonadotropin-releasing hormone (GnRH) deficiency. Given the close developmental association of GnRH neurons with the olfactory primary axons, CHH is often associated with anosmia or hyposmia, in which case it is defined as Kallmann syndrome (KS). The genetics of CHH are heterogeneous, and >40 genes are involved either alone or in combination. Several CHH-related genes controlling GnRH ontogeny encode proteins containing fibronectin-3 (FN3) domains, which are important for brain and neural development. Therefore, we hypothesized that defects in other FN3-superfamily genes would underlie CHH. Next-generation sequencing was performed for 240 CHH unrelated probands and filtered for rare, protein-truncating variants (PTVs) in FN3-superfamily genes. Compared to gnomAD controls the CHH cohort was statistically enriched for PTVs in neuron-derived neurotrophic factor (NDNF) (p = 1.40 x 10(-6)). Three heterozygous PTVs (p.Lys62*, p.Tyr128Thrfs*55, and p.Trp469*, all absent from the gnomAD database) and an additional heterozygous missense mutation (p.Thr201Ser) were found in four KS probands. Notably, NDNF is expressed along the GnRH neuron migratory route in both mouse embryos and human fetuses and enhances GnRH neuron migration. Further, knock down of the zebrafish ortholog of NDNF resulted in altered GnRH migration. Finally, mice lacking Ndnf showed delayed GnRH neuron migration and altered olfactory axonal projections to the olfactory bulb; both results are consistent with a role of NDNF in GnRH neuron development. Altogether, our results highlight NDNF as a gene involved in the GnRH neuron migration implicated in KS.Peer reviewe

Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins

Animal studies have suggested that angiopoietin-like 4 (Angptl4) regulates adiposity through central and peripheral mechanisms. The aim of this study was to investigate whether serum concentration and adipose tissue expression of Angptl4 are associated with obesity-related parameters in humans. Altogether, 75 dizygotic (DZ) and 46 monozygotic (MZ) twin pairs were studied, from the FinnTwin12 and FinnTwin16 cohorts. Among the MZ pairs, 21 were discordant for body mass index (BMI) (intra-pair BMI-difference >2.5 kg/m², age 23-33 years). Serum Angptl4 (s-Angptl4) levels were measured by ELISA, and adipose tissue gene expression was analyzed by genome-wide transcript profiling. In MZ twin pairs discordant for BMI, s-Angptl4 and adipose tissue ANGPTL4 mRNA (at-ANGPTL4) levels were significantly decreased (P = 0.04 and P = 0.03, respectively) in obese twins as compared with their nonobese cotwins. In all twins, intra-pair differences in s-Angptl4 levels were inversely correlated with intra-pair differences in BMI (r = -0.27, P = 0.003). In individual MZ twins, at-ANGPTL4 expression was inversely correlated with BMI (r = -0.44, P = 0.001) and positively correlated with at-LIPE (r = 0.24, P = 0.01) and at-ABHD5 (r = 0.41, P = 0.005) expression. Our results demonstrated that variation in Angptl4 concentration was only modestly accounted for by genetic factors and suggest a role for Angptl4 in acquired obesity in humans.Peer reviewe

The Finnish Think Tank Landscape : A Mixture of Consensualism and Adversity?

As a common feature of Nordic countries, the Finnish landscape of thinks tanks has been populated by large corporatist interest organisations and government-funded research organisations. In addition to this, since 2005, party-affiliated think tanks form a notable part of the picture. Recently, several small think tanks that are oriented towards specific themes, such as international relations, the environment and feminism, have been founded. This article examines Finnish developments in the field of think tanks with two objectives. First, it gives a general overview of the Finnish think tank landscape. Second, by using interview data and public mission statements of the most prominent think tanks, it explores how these organisations see their role in Finnish society. What is their relationship with media and the political machinery, and how does this relate to their position and activities as either consensual or adversarial actors? It is concluded that redeeming the place of think tanks in the Finnish polity is a continuing challenge, and resorting to adversarial tactics is not a favourable way to do so. This approach has mostly been attempted by neoliberal think tanks that, in the past, have also profited from corporatist structures to enhance their objectives.Peer reviewe

Anti-Müllerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone

STUDY QUESTION: Does treatment of constitutional delay of growth and puberty (CDGP) in boys with aromatase inhibitor letrozole (Lz) or conventional low-dose testosterone (T) have differing effects on developing seminiferous epithelium?SUMMARY ANSWER: Anti-Mullerian hormone (AMH) declined similarly in both treatment groups, and the two Sertoli cell-derived markers (AMH and inhibin B (iB)) exhibited differing responses to changes in gonadotrophin milieu.WHAT IS KNOWN ALREADY: Boys with CDGP may benefit from puberty-inducing medication. Peroral Lz activates gonadotrophin secretion, whereas intramuscular low-dose T may transiently suppress gonadotrophins and iB.STUDY DESIGN, SIZE, DURATION: Sera of 28 boys with CDGP who participated in a randomised, controlled, open-label trial at four paediatric centres in Finland between August 2013 and January 2017 were analysed. The patients were randomly assigned to receive either Lz (2.5 mg/day) (n = 15) or T (I mg/kg/month) (n = 13) for 6 months.PARTICIPANTS/MATERIALS, SETTING, METHODS: The 28 patients were at least 14 years of age, showed first signs of puberty, wanted medical attention for CDGP and were evaluated at 0, 3, 6 and 12 months of visits. AMH levels were measured with an electrochemiluminescence immunoassay and L2 levels with liquid chromatography coupled with tandem mass spectrometry.MAIN RESULTS AND THE ROLE OF CHANCE: AMH levels decreased in both treatment groups during the 12-month follow-up (P LIMITATIONS, REASONS FOR CAUTION: The original trial was not blinded for practical reasons and included a limited number of participants.WIDER IMPLICATIONS OF THE FINDINGS: In early puberty, treatment-induced gonadotrophin stimulus was unable to counteract the androgen-mediated decrease in AMH, while changes in iB levels were associated with changes in gonadotrophin levels. AMH decreased similarly in both groups during the treatment, reassuring safety of developing seminiferous epithelium in both treatment approaches. Since a fixed dose of Li induced variable serum Lz levels with a desired puberty-promoting effect in all boys, more research is needed to aim at a minimal efficient dose per weight.</div

Role of the Two Component Signal Transduction System CpxAR in Conferring Cefepime and Chloramphenicol Resistance in Klebsiella pneumoniae NTUH-K2044

Background: Klebsiella pneumoniae is a Gram-negative, non-motile, facultative anaerobe belonging to the Enterobacteriaceae family of the c-Proteobacteria class in the phylum Proteobacteria. Multidrug resistant K. pneumoniae have caused major therapeutic problems worldwide due to emergence of extended-spectrum b-lactamase producing strains. Twocomponent systems serve as a basic stimulus-response coupling mechanism to allow organisms to sense and respond to changes in many different environmental conditions including antibiotic stress. Principal Findings: In the present study, we investigated the role of an uncharacterized cpxAR operon in bacterial physiology and antimicrobial resistance by generating isogenic mutant (DcpxAR) deficient in the CpxA/CpxR component derived from the hyper mucoidal K1 strain K. pneumoniae NTUH-K2044. The behaviour of DcpxAR was determined under hostile conditions, reproducing stresses encountered in the gastrointestinal environment and deletion resulted in higher sensitivity to bile, osmotic and acid stresses. The DcpxAR was more susceptible to b-lactams and chloramphenicol than the wild-type strain, and complementation restored the altered phenotypes. The relative change in expression of acrB, acrD, eefB efflux genes were decreased in cpxAR mutant as evidenced by qRT-PCR. Comparison of outer membrane protein profiles indicated a conspicuous difference in the knock out background. Gel shift assays demonstrated direct binding of CpxR KP to promoter region of ompC KP in a concentration dependent manner

Reversible Congenital Hypogonadotropic Hypogonadism in Patients with CHD7, FGFR1 or GNRHR Mutations

Peer reviewe

Adaptable Functionality of Transcriptional Feedback in Bacterial Two-Component Systems

A widespread mechanism of bacterial signaling occurs through two-component systems, comprised of a sensor histidine kinase (SHK) and a transcriptional response regulator (RR). The SHK activates RR by phosphorylation. The most common two-component system structure involves expression from a single operon, the transcription of which is activated by its own phosphorylated RR. The role of this feedback is poorly understood, but it has been associated with an overshooting kinetic response and with fast recovery of previous interrupted signaling events in different systems. Mathematical models show that overshoot is only attainable with negative feedback that also improves response time. Our models also predict that fast recovery of previous interrupted signaling depends on high accumulation of SHK and RR, which is more likely in a positive feedback regime. We use Monte Carlo sampling of the parameter space to explore the range of attainable model behaviors. The model predicts that the effective feedback sign can change from negative to positive depending on the signal level. Variations in two-component system architectures and parameters may therefore have evolved to optimize responses in different bacterial lifestyles. We propose a conceptual model where low signal conditions result in a responsive system with effectively negative feedback while high signal conditions with positive feedback favor persistence of system output