Salicylate toxicity model of tinnitus

Salicylate, the active component of the common drug aspirin, has mild analgesic, antipyretic, and anti-inflammatory effects at moderate doses. At higher doses, however, salicylate temporarily induces moderate hearing loss and the perception of a high-pitch ringing in humans and animals. This phantom perception of sound known as tinnitus is qualitatively similar to the persistent subjective tinnitus induced by high-level noise exposure, ototoxic drugs, or aging, which affects ∼14% of the general population. For over a quarter century, auditory scientists have used the salicylate toxicity model to investigate candidate biochemical and neurophysiological mechanisms underlying phantom sound perception. In this review, we summarize some of the intriguing biochemical and physiological effects associated with salicylate-induced tinnitus, some of which occur in the periphery and others in the central nervous system. The relevance and general utility of the salicylate toxicity model in understanding phantom sound perception in general are discussed

A Data-Driven Approach to Violin Making

Of all the characteristics of a violin, those that concern its shape are probably the most important ones, as the violin maker has complete control over them. Contemporary violin making, however, is still based more on tradition than understanding, and a definitive scientific study of the specific relations that exist between shape and vibrational properties is yet to come and sorely missed. In this article, using standard statistical learning tools, we show that the modal frequencies of violin tops can, in fact, be predicted from geometric parameters, and that artificial intelligence can be successfully applied to traditional violin making. We also study how modal frequencies vary with the thicknesses of the plate (a process often referred to as {\em plate tuning}) and discuss the complexity of this dependency. Finally, we propose a predictive tool for plate tuning, which takes into account material and geometric parameters

The potential association between gingival crevicular fluid inflammatory mediators and adverse pregnancy outcomes: a systematic review

Objectives: The association between periodontal disease and adverse pregnancy outcomes (APO), primarily preterm birth (PTB), is still controversially discussed in the literature. Therefore, the aim of the present systematic review was to analyze the existing literature on the potential association between inflammatory mediators detected in gingival crevicular fluid (GCF) and APO. Materials and methods: MEDLINE (PubMed) and EMBASE databases were searched for entries up to April 2012 and studies were selected by two independent reviewers. Results: The majority of the eight studies included confirmed a positive association between GCF mediators, such as interleukin-1β, prostaglandin E2, and tumor necrosis factor-alpha, and APO. Due to the heterogeneity and variability of the available studies, no meta-analysis could be performed. Conclusions: A positive association between GCF inflammatory mediator levels and APO/PTB might be present but the results need to be considered with great caution because of the heterogeneity and variability among the studies. Further studies with an adequate number of patients allowing for an appropriate analysis are warranted to definitely confirm this association. Clinical relevance: The present findings suggest that an association between GCF inflammatory mediator levels and APO might exis

Enhanced transmission beyond the cut-off through sub-Lambda Annular Aperture Arrays

A cascaded structure of annular aperture arrays perforated in silver films is shown to act as a high quality Fabry-Pérot interferometer (quality factor up to 200). The transmission of a single nanostructured layer exhibits a cut-off wavelength beyond which there is no transmission. It is demonstrated, here, that the double structure permits to overcome this cut-off. It is also found that transmission is enhanced by a factor of 150 for certain wavelengths. This kind of cascaded nanostructured metallic layers offers many promising applications as well as for optical wavelengths than for THz-waves because this effect still exists for perfect metals. It opens up the path for the conception of a new generation of integrated components based on metallo-dielectric structures that can be easily tailored as tunable devices

Prediction of subplastidial localization of chloroplast proteins from spectral count data - Comparison of machine learning algorithms

To study chloroplast metabolism and functions, subplastidial localization is a prerequisite to achieve protein functional characterization. As the accurate localization of many chloroplast proteins often remains hypothetical, we set up a proteomics strategy in order to assign the accurate subplastidial localization. A comprehensive study of Arabidopsis thaliana chloroplast proteome has been carried out in our group [1], involving high performance mass spectrometry analyses of highly fractionated chloroplasts. In particular, spectral count data were acquired for the three major chloroplast sub-fractions (stroma, thylakoids and envelope) obtained by sucrose gradient purification. As the distribution of spectral counts over compartments is a fair predicator of relative abundance of proteins [2], it was justified to propose a prime statistical model [1] relating spectral counts to subplastidial localization. This predictive model was based on a logistic regression, and demonstrated an accuracy rate of 84% for chloroplast proteins. In the present work, we conducted a comparative study of various machine learning techniques to generate a predictive model of subplastidial localization of chloroplast proteins based on spectral count data

Plasma Androgen Receptor and Docetaxel for Metastatic Castration-resistant Prostate Cancer

Càncer de pròstata; Receptor d'andrògens; DocetaxelCáncer de próstata; Receptor de andrógenos; DocetaxelProstate cancer; Androgen receptor; DocetaxelPlasma androgen receptor (AR) gain identifies metastatic castration-resistant prostate cancer (mCRPC) patients with worse outcome on abiraterone/enzalutamide, but its relevance in the context of taxane chemotherapy is unknown. We aimed to evaluate whether docetaxel is active regardless of plasma AR and to perform an exploratory analysis to compare docetaxel with abiraterone/enzalutamide. This multi-institutional study was a pooled analysis of AR status, determined by droplet digital polymerase chain reaction, on pretreatment plasma samples. We evaluated associations between plasma AR and overall/progression-free survival (OS/PFS) and prostate-specific antigen (PSA) response rate in 163 docetaxel-treated patients. OS was significantly shorter in case of AR gain (hazard ratio [HR]=1.61, 95% confidence interval [CI]=1.08-2.39, p=0.018), but not PFS (HR=1.04, 95% CI 0.74-1.46, p=0.8) or PSA response (odds ratio=1.14, 95% CI=0.65-1.99, p=0.7). We investigated the interaction between plasma AR and treatment type after incorporating updated data from our prior study of 73 chemotherapy-naïve, abiraterone/enzalutamide-treated patients, with data from 115 first-line docetaxel patients. In an exploratory analysis of mCRPC patients receiving first-line therapies, a significant interaction was observed between plasma AR and docetaxel versus abiraterone/enzalutamide for OS (HR=0.16, 95% CI=0.06-0.46, p<0.001) and PFS (HR=0.31, 95% CI=0.12-0.80, p=0.02). Specifically, we reported a significant difference for OS favoring abiraterone/enzalutamide for AR-normal patients (HR=1.93, 95% CI=1.19-3.12, p=0.008) and a suggestion favoring docetaxel for AR-gained patients (HR=0.53, 95% CI=0.24-1.16, p=0.11). These data suggest that AR-normal patients should receive abiraterone/enzalutamide and AR-gained could benefit from docetaxel. This treatment selection merits prospective evaluation in a randomized trial. PATIENT SUMMARY: We investigated whether plasma androgen receptor (AR) predicted outcome in metastatic castration-resistant prostate cancer (mCRPC) patients treated with docetaxel, and we performed an exploratory analysis in patients treated with docetaxel or AR-directed drugs as first-line mCRPC therapy. We showed that plasma AR normal favored hormonal treatment, whilst plasma AR-gained patients may have had a longer response to docetaxel, suggesting that plasma AR status could be a useful treatment selection biomarker.Funding/Support and role of the sponsor: V. Conteduca was funded by a European Society of Medical Oncology Translational Clinical Research Fellowship. A. Jayaram is supported by a grant from the Medical Research Council (MR/P002072/1). G. Attard is supported by a Cancer Research UK Advanced Clinician Scientist Grant (A22744). This work was funded in part by Prostate Cancer UK (PG12-49), the “Instituto de Salud Carlos III” (ISCII) PI16/01565 grant. E. Gonzalez-Billalabeitia was funded by a grant from the “Instituto de Salud Carlos III” (ISCIII) PI15/01499. N. RomeroLaorden was funded by a grant from the “Instituto de Salud Carlos III” (CM14-00200). E. Castro is supported by a Prostate Cancer Foundation Young Investigator Award (2017). E. Castro and D. Olmos are supported by grants from the Ministerio de Economía, Industria y Competitividad (JCI-2014-19129 to E.C., RYC-2015-18625 to D.O.). B. Mellado and M. Marin-Aguilera work were supported by the Instituto de Salud Carlos IIISubdirección General de Evaluación y Fomento de la Investigación (PI12/ 01226 and PI15/676) and co-funded by the European Regional Development Fund. Funding from CERCA Programme/Generalitat de Catalunya is gratefully acknowledged. During the conduct of the study, E. Castro was supported by a grant from the Ministerio de Educación, Cultura y Deportes (CAS17/00182). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding authors had full access to all data and had the final responsibility for the decision to submit for publication

Evaluation of Safety and Efficacy of ReHub in Patients Who Underwent Primary Total Knee Arthroplasty: Study Protocol for a Randomized Controlled Trial

Background: Total Knee Arthroplasty (TKA) is an intervention that can significantly improve the quality of life of patients with advanced knee osteoarthritis. Early start of rehabilitation and its continuation at home once the patient is discharged are key factors for the success of the process.This study aims to assess the effectiveness of a home-based telerehabilitation solution (ReHub) on improving functional capacity and clinical outcomes for patients who underwent TKA. Methods/design: The study is a randomized, open-label with blinded outcome assessor, parallel assignment clinical trial with a sample size of 52 patients that is conducted according to the SPIRIT recommendations. After the TKA intervention, the patients are randomly allocated to the control group or the experimental group with a 1:1 ratio. Both groups follow a Fast Track recovery protocol which includes discharge after 2-3 days from surgery, a daily plan of 5 exercises for autonomous rehabilitation and domiciliary visits by a physiotherapist starting approximately 2 weeks after surgery. The experimental group uses the sensor-based telerehabilitation system ReHub to perform the exercises. The primary outcome measure is the range of motion of the knee. Secondary outcomes include physical performance, quality of life, pain intensity, muscle strength, treatment adherence and satisfaction with the ReHub system. The outcomes assessment is performed at hospital discharge (baseline), at stitch removal (2 weeks after baseline) and 2 weeks after stitch removal (4 weeks after baseline).The study conforms to the guidelines of the Declaration of Helsinki and was approved by the hospital's ethics committee. Discussion: The study will address an important gap in the evidence base by reporting the effectiveness of an affordable and low-cost home-based telerehabilitation solution in patients who underwent TKA. Ethics and dissemination: The study was approved by the hospital's ethics committee ("Comité Ético de Investigación Clínica del HCB", reg. HCB/2019/0571). The trial was registred at ClinicalTrials.gov (NCT04155957). The results of this study will be published in peer-reviewed journals as well as national and international conferences. Trial registration: NCT04155957 (ClinicalTrials.gov). Highlights: Assessing a home-based telerehabilitation solution effectiveness in knee surgery.In situations such as the CoVid-19 pandemic, it is a resolutive intervention method.Telerehabilitation is an alternative to conventional face-to-face physical therapy.This system is far less demanding in terms of human resources.Range of motion assessment is the primary outcome measure

Lactococcus lactis, an Alternative System for Functional Expression of Peripheral and Intrinsic Arabidopsis Membrane Proteins

International audienceBACKGROUND: Despite their functional and biotechnological importance, the study of membrane proteins remains difficult due to their hydrophobicity and their low natural abundance in cells. Furthermore, into established heterologous systems, these proteins are frequently only produced at very low levels, toxic and mis- or unfolded. Lactococcus lactis, a gram-positive lactic bacterium, has been traditionally used in food fermentations. This expression system is also widely used in biotechnology for large-scale production of heterologous proteins. Various expression vectors, based either on constitutive or inducible promoters, are available for this system. While previously used to produce bacterial and eukaryotic membrane proteins, the ability of this system to produce plant membrane proteins was until now not tested. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this work was to test the expression, in Lactococcus lactis, of either peripheral or intrinsic Arabidopsis membrane proteins that could not be produced, or in too low amount, using more classical heterologous expression systems. In an effort to easily transfer genes from Gateway-based Arabidopsis cDNA libraries to the L. lactis expression vector pNZ8148, we first established a cloning strategy compatible with Gateway entry vectors. Interestingly, the six tested Arabidopsis membrane proteins could be produced, in Lactococcus lactis, at levels compatible with further biochemical analyses. We then successfully developed solubilization and purification processes for three of these proteins. Finally, we questioned the functionality of a peripheral and an intrinsic membrane protein, and demonstrated that both proteins were active when produced in this system. CONCLUSIONS/SIGNIFICANCE: Altogether, these data suggest that Lactococcus lactis might be an attractive system for the efficient and functional production of difficult plant membrane proteins