Identification of candidate host serum and saliva biomarkers for a better diagnosis of active and latent tuberculosis infection

In our work, we aim to identify new candidate host biomarkers to discriminate between active TB patients (n = 28), latent infection (LTBI; n = 27) and uninfected (NoTBI; n = 42) individuals. For that, active TB patients and their contacts were recruited that donated serum and saliva samples. A multiplex assay was performed to study the concentration of different cytokines, chemokines and growth factors. Proteins with significant differences between groups were selected and logistic regression and the area under the ROC curve (AUC) was used to assess the diagnostic accuracy. The best marker combinations that discriminate active TB from NoTBI contacts were [IP-10 + IL-7] in serum and [Fractalkine + IP-10 + IL-1alpha + VEGF] in saliva. Best discrimination between active TB and LTBI was achieved using [IP-10 + BCA-1] in serum (AUC = 0.83) and IP-10 in saliva (p = 0.0007; AUC = 0.78). The levels of TNFalpha (p = 0.003; AUC = 0.73) in serum and the combination of [Fractalkine+IL-12p40] (AUC = 0.83) in saliva, were able to differentiate between NoTBI and LTBI contacts. In conclusion, different individual and combined protein markers could help to discriminate between active TB and both uninfected and latently-infected contacts. The most promising ones include [IP-10 + IL-7], [IP-10 + BCA-1] and TNFalpha in serum and [Fractalkine + IP-10 + IL-1alpha + VEGF], IP-10 and [Fractalkine+IL-12p40] in saliva

Study of size effects on the peak and residual strength of intact and artificially fissured granite samples

There are not many studies on jointed rock specimens, which can be considered small scale rock mass analogs. On the other hand, the scale effects in the mechanical properties of such samples have seldom been studied. With the aim of continuing previous research on intact granite rocks, the authors have carried out sets of 25 stress-strain triaxial compressive tests on 1 sub-vertical and 2 sub-horizontal 38 mm, 54 mm and 84 mm diameter jointed granite specimens at various confinements. Peak and residual strength values were obtained and compared to those recovered form intact rock samples. Results suggest that peak strength follows similar trends with scale to those observed on intact rock, even if lower strength values are logically recorded. Regarding residual strength, the obtained results are in line with those observed trends for standard size samples, showing a similar trend for all cases independently of scale, even if we observe larger variability for jointed samples. The authors have also compared the values fitting the generalized Hoek-Brown criterion for rock masses to better understand the behavior in relation to sample size. So scale effects clearly appear on jointed rock peak strength of jointed sample; even if residual strength seems hardly affected by scale.Agencia Estatal de Investigación | Ref. RTI2018-093563-B-I0

Difficulties in emotion regulation, coping, and dysfunctional psychological symptoms in family members of people with gambling disorder

Gambling disorder not only affects those who suffer from it, but also has consequences for their families. Considering such repercussions are often understudied, and the aim of the present study was to evaluate the main differences between family members of people with gambling disorder (GDFMs), and those with no relatives diagnosed with gambling disorder (non-GDFMs). The variables examined in the present study included emotion regulation, coping strategies, depression, and anxiety. The sample (N=203) was divided into two groups. This comprised a clinical group (n=89 participants, 43.8% of the sample), with 69.7% of women (Mage=48.63, SD=13.36), and a community sample (i.e., no gambling-related problems in their family; n=114, representing 56.2% of the sample), containing 64% of women (Mage=35.89, SD=11.45). Results showed that GDFMs scored significantly higher than non-GDFMs (i) on anxiety and depression scales, (ii) on difficulties in emotion regulation, and (iii) on maladaptive coping strategies. Additionally, difficulties in emotion regulation and coping strategies correlated with anxiety and depression. Regression analyses showed that difficulties in emotion regulation and coping strategies predicted anxiety and depression for GDFMs. These findings highlight the importance of including family members as part of the target group in gambling disorder treatment protocols

Percutaneous treatment with Mitraclip for functional mitral regurgitation: medium-term follow up according to left ventricular function

Background: Functional mitral regurgitation (FMR) is a bad prognosis condition despite optimal medical treatment. Nowadays there is an open debate about the surgical versus percutaneous treatment. The main objective of this study is to evaluate the mid-term follow up clinical outcomes of patients with FMR treated with MitraClip((R)) system, according to their left ventricular ejection fraction (LVEF). Methods: Data was obtained from two experienced centers in transcatheter mitral valve repair (TMVR). All consecutive cases of severe FMR undergoing TMVR in both centers with the same inclusion criteria were included prospectively in this study and followed-up. Periodical follow-ups with clinical and echocardiographic evaluation were scheduled from the baseline procedure, at 3 months and then yearly. Results: From October 2015 to October 2019, a total of 119 patients with FMR at 2 centers in Spain underwent TMVR with the MitraClip((R)) procedure and were included in this study. The mean age was 73.8+/-8.9 years old and 32 patients (26.9%) were female. A 39.5% of cases [47] had a LVEF 30% (group 2). There was a similar distribution in cardiovascular risk factors, age and other diseases. All MitraClip((R)) implantations were elective and procedural success was achieved in 110 patients (92.4%) with a similar distribution between the groups. There were no differences in procedural time and the number of implanted clips. The median follow-up was 22.6 months (IQR, 11.43-34.98 months). The primary combined endpoint occurred in the 41.6% of the global cohort, 57.5% in group 1 and 30.99% in group 2 (P=0.036). LVEF was associated to the main event in the multivariate analysis (HR 2.09, 95% CI: 1.12-3.89; P=0.02). Conclusions: The MitraClip edge-to-edge technique is a safe and effective procedure for the treatment of FMR. In this study, patients with LVEF >30% treated with Mitraclip presented better clinical cardiovascular outcomes than those with a LVEF </=30%. Regardless clinical outcomes, at the end of the follow-up, there was a sustained reduction in MR grades and an important improvement in NYHA functional class

Downregulation of mTOR Signaling Increases Stem Cell Population Telomere Length during Starvation of Immortal Planarians

Reduction of caloric intake delays and prevents age-associated diseases and extends the life span in many organisms. It may be that these benefits are due to positive effects of caloric restriction on stem cell function. We use the planarian model Schmidtea mediterranea, an immortal animal that adapts to long periods of starvation by shrinking in size, to investigate the effects of starvation on telomere length. We show that the longest telomeres are a general signature of planarian adult stem cells. We also observe that starvation leads to an enrichment of stem cells with the longest telomeres and that this enrichment is dependent on mTOR signaling. We propose that one important effect of starvation for the rejuvenation of the adult stem cell pool is through increasing the median telomere length in somatic stem cells. Such a mechanism has broad implications for how dietary effects on aging are mediated at the whole-organism level.C.G.-E. was funded by a Contrato de Investigadores Miguel Servet (CP12/03214) and by the FLI. The FLI is a member of the Leibniz Association and is financially supported by the Federal Government of Germany and the State of Thuringia. O.G.-G. was funded by an LGSA scholarship. R.P. and B.F.-V. were funded by a grant (PI17-01401) from Fondo de Investigaciones Sanitarias (Instituto de Salud Carlos III, Spain) and FEDER funds. I.F. was funded by grants from Ministerio de Ciencia, Innovación y Universidades (SAF2016-80406-R), Comunidad de Madrid (S2017/BMD-3875), and the Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares (RD12/0042/0045). The CNIC is supported by the Ministerio de Ciencia, Innovación y Universidades and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505). A.A.A. was funded by grants from the BBSRC (BB/K007564/1) and MRC (MR/M000133/1), and S.S. by a University of Oxford Clarendon Fund Scholarship.S

Ventricular arrhythmias in patients with functional mitral regurgitation and implantable cardiac devices: implications of mitral valve repair with Mitraclip

Background: Limited information has been reported regarding the impact of percutaneous mitral valve repair (PMVR) on ventricular arrhythmic (VA) burden. The aim of this study was to address the incidence of VA and appropriate antitachycardia implantable cardiac defibrillator (ICD) therapies before and after PMVR. Methods: We retrospectively analyzed all consecutive patients with heart failure with reduce left ventricular ejection fraction (LVEF), functional mitral regurgitation (FMR) grade 3+ or 4+ and an active ICD or cardiac resynchronizer who underwent PMVR in any of the eleven recruiting centers. Only patients with complete available device VA monitoring from one-year before to one year after PMVR were included. Baseline clinical and echocardiographic characteristics were collected before PMVR and at 12-months follow-up. Results: Ninety-three patients (68.2+/-10.9 years old, male 88.2%) were enrolled. PMVR was successfully performed in all patients and device success at discharge was 91.4%. At 12-month follow-up, we observed a significant reduction in mitral regurgitation severity, NT-proBNP and prevalence of severe pulmonary hypertension and severe kidney disease. Patients also referred a significant improvement in NYHA functional class and showed a non-significant trend to reserve left ventricular remodeling. After PMVR a significant decrease in the incidence of non-sustained ventricular tachycardia (VT) (5.0+/-17.8 vs. 2.7+/-13.5, P=0.002), sustained VT or ventricular fibrillation (0.9+/-2.5 vs. 0.5+/-2.9, P=0.012) and ICD antitachycardia therapies (2.5+/-12.0 vs. 0.9+/-5.0, P=0.033) were observed. Conclusions: PMVR was related to a reduction in arrhythmic burden and ICD therapies in our cohort

Power device losses in two-level converters with direct current controllers for grid connected applications

Direct current controllers have been widely used in grid-tied applications and electric drives. Direct controllers select the switching states of the converter without the intervention of a modulation stage. In comparison with PWM based controllers, direct controllers have a faster dynamic response to reference-tracking and disturbance rejection. The different control strategies can affect the total converter losses and device loss distribution; hence it is important to evaluate them when novel control methodologies are presented and compare them to the conventional PWM current controllers. To this end, fully electrothermal simulations can be paramount. Using a grid connected two-level converter, this paper evaluates the power device losses and the resulting junction temperatures excursions of the power semiconductors chips when a direct current controller is used and compares the results to those obtained with PWM controllers working at the same operating points

SMG-1 and mTORC1 Act Antagonistically to Regulate Response to Injury and Growth in Planarians

Planarian flatworms are able to both regenerate their whole bodies and continuously adapt their size to nutrient status. Tight control of stem cell proliferation and differentiation during these processes is the key feature of planarian biology. Here we show that the planarian homolog of the phosphoinositide 3-kinase-related kinase (PIKK) family member SMG-1 and mTOR complex 1 components are required for this tight control. Loss of smg-1 results in a hyper-responsiveness to injury and growth and the formation of regenerative blastemas that remain undifferentiated and that lead to lethal ectopic outgrowths. Invasive stem cell hyper-proliferation, hyperplasia, hypertrophy, and differentiation defects are hallmarks of this uncontrolled growth. These data imply a previously unappreciated and novel physiological function for this PIKK family member. In contrast we found that planarian members of the mTOR complex 1, tor and raptor, are required for the initial response to injury and blastema formation. Double smg-1 RNAi experiments with tor or raptor show that abnormal growth requires mTOR signalling. We also found that the macrolide rapamycin, a natural compound inhibitor of mTORC1, is able to increase the survival rate of smg-1 RNAi animals by decreasing cell proliferation. Our findings support a model where Smg-1 acts as a novel regulator of both the response to injury and growth control mechanisms. Our data suggest the possibility that this may be by suppressing mTOR signalling. Characterisation of both the planarian mTORC1 signalling components and another PIKK family member as key regulators of regeneration and growth will influence future work on regeneration, growth control, and the development of anti-cancer therapies that target mTOR signalling

Effectiveness of rotavirus vaccination in Spain

With the aim of determining rotavirus vaccine effectiveness (RVVE) in Spain, from Oct-2008/Jun-2009, 467 consecutive children below 2 years old with acute gastroenteritis (AGE) were recruited using a pediatric research network (ReGALIP-www.regalip.org) that includes primary, emergency and hospital care settings. Of 467 enrolled children, 32.3% were rotavirus positive and 35.0% had received at least one dose of any rotavirus vaccine. RRVE to prevent any episode of rotavirus AGE was 91.5% (95% CI: 83.7%-95.6%). RVVE to prevent hospitalization by rotavirus AGE was 95.6% (85.6-98.6%). No differences in RVVE were found regarding the vaccine used. Rotavirus vaccines have showed an outstanding effectiveness in Spain

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13