Mediation of perceived stress and cortisol in the association between neuroticism and global cognition in older adults: A longitudinal study

Neuroticism has been associated with a greater dementia risk, but its association with cognitive decline in healthy older adults remains unclear. Stress has been proposed as one of the mechanisms that could explain this relationship. Our aim was to analyse, in healthy older people, the mediating role of perceived stress and the Hypothalamic–Pituitary–Adrenal (HPA) axis in the association between neuroticism and global cognition. At Waves 1 and 2 (4-year follow-up), 87 older people (49.4% women; M age = 65.08, SD = 4.54 at Wave 1) completed a neuropsychological battery and the Perceived Stress Scale (PSS), and provided saliva samples on two (Wave 1) and three (Wave 2) consecutive days to measure the wake-to-bed slope. In Wave 2, neuroticism was assessed with the NEO-Five-Factor Inventory. PSS, but not the wake-to-bed slope, mediated the negative associations between neuroticism and global cognition (Waves 1, 2 and change). Regarding gender differences, PSS (Waves 1, 2 and change) and the wake-to-bed slope (Wave 2 and change) mediated these associations in men. Our results suggest that perceived stress and HPA-axis dysregulation could act as mechanisms underlying the association between neuroticism and cognitive functioning and decline, at least in older men. © 2021. The Authors. Stress and Health published by John Wiley & Sons Ltd

Efficacy and Safety of Netakimab, A Novel Anti-IL-17 Monoclonal Antibody, in Patients with Moderate to Severe Plaque Psoriasis. Results of A 54-Week Randomized Double-Blind Placebo-Controlled PLANETA Clinical Trial

Altres ajuts: Sponsorship for this study and the Rapid Service Fee were funded by JSC BIOCAD, Ul. Italianskaya 17, St Petersburg, Russia, 191186Introduction: Netakimab (NTK), an original humanized anti-interleukin-17 monoclonal antibody, showed therapeutic efficacy in moderate-to-severe plaque psoriasis in a phase 2 clinical study. Herein we report the results of 54 weeks of a phase 3 PLANETA trial aimed to evaluate the efficacy and safety of two NTK regimens vs. placebo. Methods: Two hundred thirteen patients with moderate-to-severe plaque psoriasis were randomly assigned to receive NTK 120 mg once every 2 weeks (NTK Q2W), NTK 120 mg once every 4 weeks (NTK Q4W) or placebo. During the first 3 weeks, patients received subcutaneous injections of NTK or placebo (according to the allocation) once a week. Patients in the NTK Q2W group then received NTK at weeks 4, 6, 8 and 10. Subjects in the NTK Q4W group received NTK at weeks 6 and 10 and placebo at weeks 4 and 8. Patients in the placebo group received placebo injections at weeks 4, 6, 8 and 10. Treatment was unblinded at week 12. During the open-label phase, patients in both NTK groups continued to receive NTK Q4W. The primary efficacy endpoint was the proportion of patients in each group who achieved a ≥ 75% reduction from baseline in psoriasis area and severity index (PASI 75) at week 12. Results: A total of 77.7%, 83.3% and 0% of patients had a PASI 75 response at week 12 in the NTK Q2W, NTK Q4W and placebo groups, respectively (P < 0.0001, Fisher's exact test, ITT). The effect was maintained throughout the 1-year treatment. NTK showed a good safety profile and low immunogenicity. Conclusion: Treatment with NTK results in high rates of sustained clinical response in patients with moderate-to-severe plaque psoriasis. The study is ongoing; thus, long-term use efficacy and safety data are forthcoming. Clinical Trial Registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT03390101)

Evidencias farmacológicas de la participación del sistema opioide endógeno en la respuesta inflamatoria local de la pata de la rata

Hemos investigado el papel del sistema opioide endógeno (SOE) en la respuesta inflamatoria inducida por la inyección subplantar (SP) de salino (SS) y carragenina (CA) en la pata trasera de la rata. Se usó naloxona intraperitoneal (IP) para desenmascarar los efectos de los opiáceos endógenos liberados durante la inflamación periférica. Tres grupos de ratas recibieron uno de los siguientes tratamientos SP: SS, CA o ninguna inyección (NI). En condiciones basales y 3 horas después del tratamiento fueron evaluados el umbral del dolor por presión (PPT), el volúmen de la pata (edema) y la temperatura local. En cada grupo fueron también investigados los efectos del vehículo IP, naloxona y (+)-naloxona (0,1 mg/kg). Los grupos SS y CA indujeron una significativa respuesta inflamatoria con hiperalgesia, edema e hiperemia local. La administración IP de naloxona pero no de (+)-naloxona, 15 minutos antes de la prueba, incrementó significativamente el edema en todos los grupos de tratamiento (p< 0,05) sin alterar el PPT o la temperatura local. El ANOVA de dos vías, reveló que el tratamiento y los fármacos, así como sus interacciones tenían un impacto significativo en el edema el cual estaba relacionado con los efectos de la CA y la naloxona. Nuestros hallazgos ilustran la implicación del sistema opioide endógeno a la respuesta fisiológica a la lesión local, regulando la fuga microvascular en los tejidos inflamados

Cantor and band spectra for periodic quantum graphs with magnetic fields

We provide an exhaustive spectral analysis of the two-dimensional periodic square graph lattice with a magnetic field. We show that the spectrum consists of the Dirichlet eigenvalues of the edges and of the preimage of the spectrum of a certain discrete operator under the discriminant (Lyapunov function) of a suitable Kronig-Penney Hamiltonian. In particular, between any two Dirichlet eigenvalues the spectrum is a Cantor set for an irrational flux, and is absolutely continuous and has a band structure for a rational flux. The Dirichlet eigenvalues can be isolated or embedded, subject to the choice of parameters. Conditions for both possibilities are given. We show that generically there are infinitely many gaps in the spectrum, and the Bethe-Sommerfeld conjecture fails in this case.Comment: Misprints correcte

Long-term safety and efficacy of risankizumab for the treatment of moderate-to-severe plaque psoriasis : Interim analysis of the LIMMitless open-label extension trial up to 5 years of follow-up

Psoriasis is a chronic, inflammatory skin disease often requiring long-term therapy. To evaluate the long-term safety and efficacy of risankizumab in patients with psoriasis. Methods: LIMMitless is an ongoing phase 3, open-label extension study evaluating the long-term safety and efficacy of continuous risankizumab 150 mg every 12 weeks for adults with moderate-to-severe plaque psoriasis following multiple phase 2/3 base studies. This interim analysis assessed safety (ie, monitored treatment-emergent adverse events [TEAEs]) through 304 weeks. Efficacy assessments included determining the proportion of patients who achieved ≥90% or 100% improvement in Psoriasis Area and Severity Index (PASI 90/100), static Physician's Global Assessment of clear/almost clear (sPGA 0/1), and Dermatology Life Quality Index of no effect on patient's life (DLQI 0/1) through 256 weeks. Among 897 patients randomized to risankizumab in the base studies, 706 were still ongoing at data cutoff. Rates of TEAEs, TEAEs leading to discontinuation, and TEAEs of safety interest were low. At week 256, 85.1%/52.3% of patients achieved PASI 90/100, respectively, 85.8% achieved sPGA 0/1, and 76.4% achieved DLQI 0/1. Limitations: Open-label study with no placebo or active-comparator group. Long-term continuous risankizumab treatment for up to 5 years was well tolerated and demonstrated high and durable efficacy

Early outcome of a 31-gene expression profile test in 86 AJCC stage IB-II melanoma patients. A prospective multicentre cohort study

Background: The clinical and pathological features of primary melanoma are not sufficiently sensitive to accurately predict which patients are at a greater risk of relapse. Recently, a 31-gene expression profile (DecisionDx-Melanoma) test has shown promising results. Objectives: To evaluate the early prognostic performance of a genetic signature in a multicentre prospectively evaluated cohort. Methods: Inclusion of patients with AJCC stages IB and II conducted between April 2015 and December 2016. All patients were followed up prospectively to assess their risk of relapse. Prognostic performance of this test was evaluated individually and later combined with the AJCC staging system. Prognostic accuracy of disease-free survival was determined using Kaplan-Meier curves and Cox regression analysis. Results of the gene expression profile test were designated as Class 1 (low risk) and Class 2 (high risk). Results: Median follow-up time was 26 months (IQR 22-30). The gene expression profile test was performed with 86 patients; seven had developed metastasis (8.1%) and all of them were in the Class 2 group, representing 21.2% of this group. Gene expression profile was an independent prognostic factor for relapse as indicated by multivariate Cox regression analysis, adjusted for AJCC stages and age. Conclusions: This prospective multicentre cohort study, performed in a Spanish Caucasian cohort, shows that this 31-gene expression profile test could correctly identify patients at early AJCC stages who are at greater risk of relapse. We believe that gene expression profile in combination with the AJCC staging system could well improve the detection of patients who need intensive surveillance and optimize follow-up strategies

Quality control for the first large areas of triple-GEM chambers for the CMS endcaps

The CMS Collaboration plans to equip the very forward muon system with triple-GEM detectors that can withstand the environment of the High-Luminosity LHC.This project is at the final stages of R&D and moving to production. A large area of several 100 m 2 are to be instrumented with GEM detectors which will be produced in six different sites around the world. A common construction and quality control procedure is required to ensure the performance of each detector.The quality control steps will include optical inspection,cleaning and baking of all materials and parts used to build the detector,leakage current tests of the GEM foils,high voltage tests,gas leak tests of the chambers and monitoring pressures time,gain calibration to know the optimal operation region of the detector,gain uniformity tests, and studying the efficiency,noise and tracking performance of the detectors in a cosmic stand using scintillator

The effect on melanoma risk of genes previously associated with telomere length.

Telomere length has been associated with risk of many cancers, but results are inconsistent. Seven single nucleotide polymorphisms (SNPs) previously associated with mean leukocyte telomere length were either genotyped or well-imputed in 11108 case patients and 13933 control patients from Europe, Israel, the United States and Australia, four of the seven SNPs reached a P value under .05 (two-sided). A genetic score that predicts telomere length, derived from these seven SNPs, is strongly associated (P = 8.92x10(-9), two-sided) with melanoma risk. This demonstrates that the previously observed association between longer telomere length and increased melanoma risk is not attributable to confounding via shared environmental effects (such as ultraviolet exposure) or reverse causality. We provide the first proof that multiple germline genetic determinants of telomere length influence cancer risk.This is the final version of the article. It first appeared from Oxford University Press via http://dx.doi.org/10.1093/jnci/dju26

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date

Model-independent search for CP violation in D0→K−K+π−π+ and D0→π−π+π+π− decays

A search for CP violation in the phase-space structures of D0 and View the MathML source decays to the final states K−K+π−π+ and π−π+π+π− is presented. The search is carried out with a data set corresponding to an integrated luminosity of 1.0 fb−1 collected in 2011 by the LHCb experiment in pp collisions at a centre-of-mass energy of 7 TeV. For the K−K+π−π+ final state, the four-body phase space is divided into 32 bins, each bin with approximately 1800 decays. The p-value under the hypothesis of no CP violation is 9.1%, and in no bin is a CP asymmetry greater than 6.5% observed. The phase space of the π−π+π+π− final state is partitioned into 128 bins, each bin with approximately 2500 decays. The p-value under the hypothesis of no CP violation is 41%, and in no bin is a CP asymmetry greater than 5.5% observed. All results are consistent with the hypothesis of no CP violation at the current sensitivity