Garvicins AG1 and AG2 : two novel class IId bacteriocins of lactococcus garvieae Lg-Granada

Funding: This research was funded by the Spanish Ministry of Science, Innovation, and Universities, grant number RTI2018-098530-B-I00. The APC was funded by the Spanish Ministry of Science, Innovation, and Universities, grant number RTI2018-098530-B-I00.Lactococcus garvieae causes infectious diseases in animals and is considered an emerging zoonotic pathogen involved in human clinical conditions. In silico analysis of plasmid pLG50 of L. garvieae Lg-Granada, an isolate from a patient with endocarditis, revealed the presence of two gene clusters (orf 46–47 and orf 48–49), each one encoding a novel putative bacteriocin, i.e., garvicin AG1 (GarAG1; orf 46) and garvicin AG2 (GarAG2; orf 48), and their corresponding immunity proteins (orf 47 and orf 49). The chemically synthesised bacteriocins GarAG1 and GarAG2 presented inhibitory activity against pathogenic L. garvieae strains, with AG2 also being active against Listeria monocytogenes, Listeria ivanovii and Enterococcus faecalis. Genetic organisation, amino acid sequences and antimicrobial activities of GarAG1 and GarAG2 indicate that they belong to linear non-pediocin-like one-peptide class IId bacteriocins. Gram-positive bacteria that were sensitive to GarAG2 were also able to ferment mannose, suggesting that this bacteriocin could use the mannose phosphotransferase transport system (Man-PTS) involved in mannose uptake as a receptor in sensitive strains. Intriguingly, GarAG1 and GarAG2 were highly active against their own host, L. garvieae Lg-Granada, which could be envisaged as a new strategy to combat pathogens via their own weapons.Publisher PDFPeer reviewe

The prevalence of depression, anxiety and stress and their associated factors in college students

Aim: To estimate the prevalence of symptoms of depression, anxiety, stress and associated factors in a population of college students. Method: Cross-sectional study of psychological distress measured through the Depression, Anxiety and Stress Scale (DASS-21) in a sample of 1074 college students. Results: We found a moderate prevalence of depression (18, 4%), anxiety (23, 6%) and stress (34, 5%) symptoms in our study population. Being <21, having problematic Internet use behavior, smoking, presenting insomnia and having a low self-esteem were independently associated with symptoms of depression, anxiety and stress. Being a woman, living with their family, having a stable partner, consuming alcohol frequently and having poor nutritional habits were significantly associated with symptoms of stress; lacking a stable partner was significantly associated with depressive symptoms; and frequent consumption of alcohol was significantly associated with symptoms of anxiety. Conclusion: We found a moderate prevalence of depression, anxiety and stress symptoms in our population. Interventions aimed at promoting mental health among college students should be implemented

Care dependency in patients with heart failure: A cross-sectional study in Spain

Background: Heart failure (HF) is a progressive and debilitating condition that represents an ever-growing problem for health systems worldwide. HF patients feel that they are a burden on their families, they feel socially isolated and have a low perception of their health. Accordingly, the objectives of this study were to: (1) to explore the profile of care dependency in a representative sample of Spanish HF patients through the Care Dependency Scale (CDS), and (2) to identify correlates of care dependency in this population. Material and Methods: We performed a cross-sectional study of 187 patients admitted for HF decompensation to the Hospital Clínico of Zaragoza (Spain). Results: Only 15% of our sample was highly or completely dependent on care from others. More specifically, our results indicate that HF patients felt a greater level of dependency on care from others when it comes to moving, getting dressed and undressed, maintaining good personal hygiene, participating in daily and recreational activities and being continent. Conclusions: We find association between the CDS categories that present a low score for care dependency in HF patients and the patients’ physical deterioration

PCR-Based Strategy for Introducing CRISPR/Cas9 Machinery into Hematopoietic Cell Lines

Acute myeloid leukemia is a complex heterogeneous disease characterized by the clonal expansion of undifferentiated myeloid precursors. Due to the difficulty in the transfection of blood cells, several hematological models have recently been developed with CRISPR/Cas9, using viral vectors. In this study, we developed an alternative strategy in order to generate CRISPR constructs by fusion PCR, which any lab equipped with basic equipment can implement. Our PCR-generated constructs were easily introduced into hard-to-transfect leukemic cells, and their function was dually validated with the addition of MYBL2 and IDH2 genes into HEK293 cells. We then successfully modified the MYBL2 gene and introduced the R172 mutation into the IDH2 gene within NB4 and HL60 cells that constitutively expressed the Cas9 nuclease. The efficiency of mutation introduction with our methodology was similar to that of ribonucleoprotein strategies, and no off-target events were detected. Overall, our strategy represents a valid and intuitive alternative for introducing desired mutations into hard-to-transfect leukemic cells without viral transduction

Influence of age on the occurrence of adverse events in rheumatic patients at the onset of biological treatment : Data from the BIOBADASER III register

To assess whether age, at the beginning of biologic treatment, is associated with the time a first adverse event (AE) appears in patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA). All patients in the BIOBADASER registry diagnosed with RA, AS, and PsA, and classified as young ( 75 years old) at start of biological treatment were included. Factors associated with the appearance of a first AE using adjusted incidence rate ratios (IRR) (Poisson regression) were analyzed. Survival to first AE was studied by Kaplan-Meier analysis and hazard ratios (HR) by Cox regression. 2483 patients were included: 1126 RA, 680 PsA, and 677 AS. Age group stratification was as follows: 63 young, 2127 adults, 237 elderly, and 56 very elderly. Regression model revealed an increased probability of suffering a first AE at age 65 years or older [IRR elderly: 1.42 (CI95% 1.13-1.77)]. Other characteristics associated with AE were female gender, the use of DMARDs, including methotrexate, the presence of comorbidities, and the time of disease duration. Factors that had the greatest impact on survival over a first AE were age > 75 years [HR 1.50 (1.01-2.24)] and female gender [HR 1.42 (1.22-1.64)]. Age at the start of treatment and female gender are key factors associated with the appearance of a first AE with biologics. Other factors related to patient status and treatment were also associated with a first AE in rheumatic patients treated with biologics

A High Dynamic Range ASIC for Time of Flight PET with monolithic crystals

The HRFlexToT is a 16-channel ASIC for SiPM anode readout designed for Positron Emission Tomography (PET) applications that features high dynamic range (>8 bits), low input impedance, common cathode connection, high speed and low power (~3.5 mW/ch). The ASIC has been manufactured using XFAB 0.18 mm CMOS technology. The main characteristics of the HRFlexToT, compared to its predecessor, are a new energy measurement readout providing a linear Time Over Threshold (ToT) with an extended dynamic range, lower power consumption and better timing response. Initial measurements show a linearity error below 3%. Single Photon Time Resolution (SPTR) measurements performed using a Hamamatsu MPPC S13360-3050CS (3x3 mm2 pixel, 50 umm cell) shows 30% improvement with respect to the previous version of the ASIC, setting this specification in the order of 141 ps FWHM and reducing 3 times power consumption. It is important to highlight that an SPTR of 141 ps FWHM is, according to the best of our knowledge, the best resolution achieved so far for this sensor. Coincidence Time Resolution (CTR) measurements are expected to be performed during 2018

Turnos de 7 horas versus 12 horas en enfermería intensiva: vivir a contratiempo

Resumen Los turnos de trabajo tienen repercusión sobre el bienestar de los profesionales sanitarios influyendo en su calidad de vida. El objetivo principal de este estudio es describir las consecuencias que tiene el turno de trabajo diurno de 12 h respecto al de 7 h en los profesionales de enfermería que trabajan en Unidades de Cuidados Intensivos. Se trata así de un estudio descriptivo transversal en 2 hospitales de tercer nivel de Barcelona: Hospital Clínico y Hospital Vall d"Hebron (turnos de 7 h y 12 h respectivamente). La recogida de datos se ha realizado mediante cuestionario ad hoc de 29 preguntas cerradas, anónimo y autoadministrado, basado en 2 escalas: Standard Shiftwork Index y Shiftwork locus of control. Dichos datos fueron procesados a través del programa SPSS V.18.0. De las 85 encuestas realizadas 52 fueron válidas: 22 en el Hospital Clínico de Barcelona y 30 en el Hospital Vall d"Hebron. Cabe destacar que los profesionales encuestados que trabajan en turno de 12 h expresan niveles superiores de conciliación laboral y personal, concretamente en tiempo de ocio a disfrutar (× 2: 10,635; p = 0,031) y tiempo de dedicación familia-amigos, así como niveles más bajos de percepción de fatiga. No se han encontrado diferencias entre el tipo de turno y facilidad de desarrollo del trabajo profesional, a pesar de que el turno de 12 h presenta niveles más altos

A new scintillating fiber dosimeter using a single optical fiber and a CCD camera

Radiotherapy treatments become more and more accurate, using very small irradiation fields and complex dose depositions. So small dosimeters for real time and in vivo dosimetry, suitable for photons as well as for electrons beams are highly desired. In this context, a scintillating fiber dosimeter (SFD) has been developed by the Laboratoire de Physique Corpusculaire de Caen (LPC Caen), France, in collaboration with one of the French regional center for cancer treatment Centre Regional de lutte contre le cancer F. Baclesse (CRLCC F. Baclesse), Caen, France, and the ELDIM Company, Herouville, France. This plastic dosimeter is water equivalent, and it is suitable for photons as well as for electrons beams without correction. It is a real time dosimeter, with an excellent signal to noise ratio, and a spatial resolution of about a few millimeters. The aim of this study was to reduce the size of the scintillator in order to improve the spatial resolution of this dosimeter. So, a new light collection device has been developed to reduce the length of the scintillator from 1 cm to 1 mm without loss in the signal to noise ratio. The accuracy of this improved prototype has been tested by comparison with standard ionization chambers and the difference between the two devices never exceeded one percent for photon and for electron irradiation beams. A first set of commercial SFD is under completion at ELDIM and it will be soon clinically tested in several French centers for cancer treatment

Efficacy and safety of a hexanic extract of Serenoa repens (Permixon (R)) for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH): systematic review and meta-analysis of randomised controlled trials and observational studies

Objectives To comprehensively evaluate the efficacy and safety of the hexanic extract of Serenoa repens (HESr, Permixon (R); Pierre Fabre Medicament, Castres, France), at a dose of 320 mg daily, as monotherapy for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH). Materials and methods We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and prospective observational studies in patients with LUTS/BPH identified through searches in Medline, Web of Knowledge (Institute for Scientific Information), Scopus, the Cochrane Library, and bibliographic references up to March 2017. Articles studying S. repens extracts other than Permixon were excluded. Data were collected on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), nocturia, quality of life, prostate volume, sexual function, and adverse drug reactions (ADRs). Data obtained from RCTs and observational studies were analysed jointly and separately using a random effects model. A sub-group analysis was performed of studies that included patients on longer-term treatment (= 1 year). Results Data from 27 studies (15 RCTs and 12 observational studies) were included for meta-analysis (total N = 5 800). Compared with placebo, the HESr was associated with 0.64 (95% confidence interval [CI] -0.98 to -0.31) fewer voids/ night (P < 0.001) and an additional mean increase in Q(max) of 2.75 mL/s (95% CI 0.57 to 4.93; P = 0.01). When compared with a-blockers, the HESr showed similar improvements on IPSS (weighted mean difference [WMD] 0.57, 95% CI -0.27 to 1.42; P = 0.18) and a comparable increase in Q(max) to tamsulosin (WMD -0.02, 95% CI -0.71 to 0.66; P = 0.95). Efficacy assessed using the IPSS was similar after 6 months of treatment between the HESr and 5a-reductase inhibitors (5ARIs). Analysis of all available published data for the HESr showed a mean improvement in IPSS from baseline of -5.73 points (95% CI -6.91 to -4.54; P < 0.001). HESr did not negatively affect sexual function and no clinically relevant effect was observed on prostate-specific antigen. Prostate volume decreased slightly. Similar efficacy results were seen in patients treated for = 1 year (n = 447). The HESr had a favourable safety profile, with gastrointestinal disorders being the most frequent ADR (mean incidence of 3.8%). Conclusion The present meta-analysis, which includes all available RCTs and observational studies, shows that the HESr (Permixon) reduced nocturia and improved Q(max) compared with placebo and had a similar efficacy to tamsulosin and short-term 5ARI in relieving LUTS. HESr (Permixon) appears to be an efficacious and well-tolerated therapeutic option for the longterm medical treatment of LUTS/BPH

Role of targeted therapies in rheumatic patients on COVID-19 outcomes: Results from the COVIDSER study

Objectives To analyse the effect of targeted therapies, either biological (b) disease-modifying antirheumatic drugs (DMARDs), targeted synthetic (ts) DMARDs and other factors (demographics, comorbidities or COVID-19 symptoms) on the risk of COVID-19 related hospitalisation in patients with inflammatory rheumatic diseases. Methods The COVIDSER study is an observational cohort including 7782 patients with inflammatory rheumatic diseases. Multivariable logistic regression was used to estimate ORs and 95% CIs of hospitalisation. Antirheumatic medication taken immediately prior to infection, demographic characteristics, rheumatic disease diagnosis, comorbidities and COVID-19 symptoms were analysed. Results A total of 426 cases of symptomatic COVID-19 from 1 March 2020 to 13 April 2021 were included in the analyses: 106 (24.9%) were hospitalised and 19 (4.4%) died. In multivariate-adjusted models, bDMARDs and tsDMARDs in combination were not associated with hospitalisation compared with conventional synthetic DMARDs (OR 0.55, 95% CI 0.24 to 1.25 of b/tsDMARDs, p=0.15). Tumour necrosis factor inhibitors (TNF-i) were associated with a reduced likelihood of hospitalisation (OR 0.32, 95% CI 0.12 to 0.82, p=0.018), whereas rituximab showed a tendency to an increased risk of hospitalisation (OR 4.85, 95% CI 0.86 to 27.2). Glucocorticoid use was not associated with hospitalisation (OR 1.69, 95% CI 0.81 to 3.55). A mix of sociodemographic factors, comorbidities and COVID-19 symptoms contribute to patients'' hospitalisation. Conclusions The use of targeted therapies as a group is not associated with COVID-19 severity, except for rituximab, which shows a trend towards an increased risk of hospitalisation, while TNF-i was associated with decreased odds of hospitalisation in patients with rheumatic disease. Other factors like age, male gender, comorbidities and COVID-19 symptoms do play a role.