Short- and long-lasting tinnitus relief induced by transcranial direct current stimulation

A significant proportion of the population suffers from tinnitus, a bothersome auditory phantom perception that can severely alter the quality of life. Numerous experimental studies suggests that a maladaptive plasticity of the auditory and limbic cortical areas may underlie tinnitus. Accordingly, repetitive transcranial magnetic stimulation (rTMS) has been repeatedly used with success to reduce tinnitus intensity. The potential of transcranial direct current stimulation (tDCS), another promising method of noninvasive brain stimulation, to relieve tinnitus has not been explored systematically. In a double-blind, placebo-controlled and balanced order design, 20 patients suffering from chronic untreatable tinnitus were submitted to 20 minutes of 1 mA anodal, cathodal and sham tDCS targeting the left temporoparietal area. The primary outcome measure was a change in tinnitus intensity or discomfort assessed with a Visual Analogic Scale (VAS) change-scale immediately after tDCS and 1 hour later. Compared to sham tDCS, anodal tDCS significantly reduced tinnitus intensity immediately after stimulation; whereas cathodal tDCS failed to do so. The variances of the tinnitus intensity and discomfort VAS change-scales increased dramatically after anodal and cathodal tDCS, whereas they remained virtually unchanged after sham tDCS. Moreover, several patients unexpectedly reported longer-lasting effects (at least several days) such as tinnitus improvement, worsening, or changes in tinnitus features, more frequently after real than sham tDCS. Anodal tDCS is a promising therapeutic tool for modulating tinnitus perception. Moreover, both anodal and cathodal tDCS seem able to alter tinnitus perception and could, thus, be used to trigger plastic changes

Nanovaccine Delivery Approaches and Advanced Delivery Systems for the Prevention of Viral Infections: From Development to Clinical Application

open access articleViral infections causing pandemics and chronic diseases are the main culprits implicated in devastating global clinical and socioeconomic impacts, as clearly manifested during the current COVID-19 pandemic. Immunoprophylaxis via mass immunisation with vaccines has been shown to be an efficient strategy to control such viral infections, with the successful and recently accelerated development of different types of vaccines, thanks to the advanced biotechnological techniques involved in the upstream and downstream processing of these products. However, there is still much work to be done for the improvement of efficacy and safety when it comes to the choice of delivery systems, formulations, dosage form and route of administration, which are not only crucial for immunisation effectiveness, but also for vaccine stability, dose frequency, patient convenience and logistics for mass immunisation. In this review, we discuss the main vaccine delivery systems and associated challenges, as well as the recent success in developing nanomaterials-based and advanced delivery systems to tackle these challenges. Manufacturing and regulatory requirements for the development of these systems for successful clinical and marketing authorisation were also considered. Here, we comprehensively review nanovaccines from development to clinical application, which will be relevant to vaccine developers, regulators, and clinicians

Improved Hille Oscillation Criteria for Nonlinear Functional Dynamic Equations of Third-Order

This paper aims to improve Hille oscillation criteria for the third-order functional dynamic equation {p2(ξ)φγ2([p1(ξ)φγ1(y∆(ξ))]∆)}∆ + a(ξ)φγ(y(g(ξ))) = 0, on an above-unbounded time scale T. The obtained results improve related contributions reported in the literature without restrictive conditions on the time scales. To demonstrate the essential results, an example is presented. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.This research was funded by the Scientific Research Deanship at the University of Ha’il— Saudi Arabia through project number RG-21 101

Attitudes of developing world physicians to where medical research is performed and reported

Background Little is known about the influence of the site of research or publication on the impact of the research findings on clinical practice, particularly in developing countries. The International Clinical Epidemiology Network (INCLEN) is dedicated to improving the quality of health research in the Developing World through institutional capacity building for evidence based medicine, and provided the opportunity to examine the likely impact of research location and journal location on physicians' practice in a number of the participating countries. Methods Physicians from secondary and tertiary hospitals in six cities located in China, Thailand, India, Egypt and Kenya were enrolled in a cross-sectional questionnaire survey. The primary outcome measures were scores on a Likert scale reflecting stated likelihood of changing clinical practice depending on the source of the research or its publication. Results Overall, local research and publications were most likely to effect change in clinical practice, followed by North American, European and regional research/publications respectively, although there were significant variations between countries. The impact of local and regional research would be greater if the perceived research quality improved in those settings. Conclusion Conducting high quality local research is likely to be an effective way of getting research findings into practice in developing countries

Spectrofluorimetric determination of sertraline in dosage forms and human plasma through derivatization with 9-fluorenylmethyl chloroformate

<p>Abstract</p> <p>Background</p> <p>Sertraline is primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. A survey of the literature reveals that most of the reported methods are either insufficiently sensitive or tedious and require highly sophisticated and dedicated instrumentation. The proposed method is considered to be specific for determination of SER in presence of its metabolite (deaminated form).</p> <p>Results</p> <p>A sensitive, simple and specific spectrofluorimetric method was developed for the determination of sertraline (SER) in pharmaceutical formulations and biological fluids. The method is based on its reaction with 9-fluorenylmethyl chloroformate (FMOC-Cl) in borate buffer of pH 8.0 to yield a highly fluorescent derivative peaking at 315 nm after excitation at 265 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence concentration plot was rectilinear over the range of 0.05-1.0 μg mL^-1with a lower detection limit of 5.34 × 10^-3μg mL^-1and limit of quantitation of 0.016 μg mL^-1.</p> <p>Conclusions</p> <p>The proposed method was successfully applied to the analysis of commercial tablets and the results obtained were in good agreement with those obtained using the reference method. Furthermore, the method was applied for the determination of SER in spiked and real human plasma. The mean % recovery (n = 3) was 94.33 ± 1.53 and 92.00 ± 2.65, respectively. A proposal of the reaction pathway was postulated.</p

Non-Motor and Motor Features in LRRK2 Transgenic Mice

10.1371/journal.pone.0070249PLoS ONE87-POLN

Manipulation of Pre-Target Activity on the Right Frontal Eye Field Enhances Conscious Visual Perception in Humans

The right Frontal Eye Field (FEF) is a region of the human brain, which has been consistently involved in visuo-spatial attention and access to consciousness. Nonetheless, the extent of this cortical site’s ability to influence specific aspects of visual performance remains debated. We hereby manipulated pre-target activity on the right FEF and explored its influence on the detection and categorization of low-contrast near-threshold visual stimuli. Our data show that pre-target frontal neurostimulation has the potential when used alone to induce enhancements of conscious visual detection. More interestingly, when FEF stimulation was combined with visuo-spatial cues, improvements remained present only for trials in which the cue correctly predicted the location of the subsequent target. Our data provide evidence for the causal role of the right FEF pre-target activity in the modulation of human conscious vision and reveal the dependence of such neurostimulatory effects on the state of activity set up by cue validity in the dorsal attentional orienting network

Attenuation of N2 amplitude of laser-evoked potentials by theta burst stimulation of primary somatosensory cortex

Theta burst stimulation (TBS) is a special repetitive transcranial magnetic stimulation (rTMS) paradigm, where bursts of low-intensity stimuli are applied in the theta frequency. The aim of this study was to investigate the effect of neuronavigated TBS over primary somatosensory cortex (SI) on laser-evoked potentials (LEPs) and acute pain perception induced with Tm : YAG laser stimulation. The amplitude changes of the N1, N2, and P2 components of LEPs and related subjective pain rating scores of 12 healthy subjects were analyzed prior to and following continuous TBS (cTBS), intermittent TBS (iTBS), intermediate TBS (imTBS), and sham stimulation. Our results demonstrate that all active TBS paradigms significantly diminished the amplitude of the N2 component, when the hand contralateral to the site of TBS was laser-stimulated. Sham stimulation condition had no significant effect. The subjective pain perception also decreased during the experimental sessions, but did not differ significantly from the sham stimulation condition. The main finding of our study is that TBS over SI diminished the amplitude of the N2 component evoked from the contralateral side without any significant analgesic effects. Furthermore, imTBS produced responses similar to those observed by other forms of TBS induced excitability changes in the SI

FHE Over the Integers: Decomposed and Batched in the Post-Quantum Regime

Fully homomorphic encryption over the integers (FHE-OI) is currently the only alternative to lattice-based FHE. FHE-OI includes a family of schemes whose security is based on the hardness of different variants of the approximate greatest common divisor (AGCD) problem. The majority of these works is based on the noise-free variant of AGCD which is potentially weaker than the general one. In particular, the noise-free variant relies on the hardness of factoring and is thus vulnerable to quantum attacks. A lot of effort was made to port techniques from second generation lattice-based FHE (using tensoring) to FHE-OI. Gentry, Sahai and Waters (Crypto 13) showed that third generation techniques (which were later formalized using the ``gadget matrix\u27\u27) can also be ported. In this work, we propose a comprehensive study of applying third generation FHE techniques to the regime of FHE-OI. We present and analyze a third generation FHE-OI based on decisional AGCD without the noise-free assumption. We proceed to showing a batch version of our scheme where each ciphertext can encode a vector of messages and operations are performed coordinate-wise. We use a similar AGCD variant to Cheon et al.~(Eurocrypt 13) who suggested the batch approach for second generation FHE, but we do not require the noise-free component or a subset sum assumption. However, like Cheon et al., we do require circular security for our scheme, even for bounded homomorphism. Lastly, we discuss some of the obstacles towards efficient implementation of our schemes and discuss a number of possible optimizations