Selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) show similar efficacy as treatments for anxiety, obsessive-compulsive, and stress-related disorders. Hence, comparisons of adverse event rates across medications are an essential component of clinical decision-making. We aimed to compare patterns of adverse events associated with SSRIs and SNRIs in the treatment of children and adults diagnosed with these disorders through a network meta-analysis. We searched MEDLINE, PsycINFO, Embase, Cochrane, websites of regulatory agencies, and international registers from inception to 09 September 2022, for randomized controlled trials assessing the efficacy of SSRIs or SNRIs. We analyzed the proportion of participants experiencing at least one adverse event and incidence rates of 17 specific adverse events. We estimated incidence rates and odds ratios through network meta-analysis with random effects and three-level models. We analyzed 799 outcome measures from 80 studies (n = 21 338). Participants in medication groups presented higher rates of adverse events (80.22%, 95% CI 76.13–83.76) when compared to placebo groups (71.21%, 67.00–75.09). Nausea was the most common adverse event (25.71%, CI 23.96–27.54), while weight change was the least common (3.56%, 1.68–7.37). We found higher rates of adverse events of medications over placebo for most medications, except sertraline and fluoxetine. We found significant differences between medications for overall tolerability and for autonomic, gastrointestinal, and sleep-related symptoms. Adverse events are a common reason that patients discontinue SSRIs and SNRIs. Results presented here guide clinical decision-making when clinicians weigh one medication over another. This might improve treatment acceptability and compliance.

Background: ALS is a progressive neurodegenerative disease without a cure and limited treatment options. Edaravone, a free radical scavenger, was shown to slow disease progression in a select group of patients with ALS over 6 months; however, the effect on survival was not investigated in randomized trials. The objective of this study is to describe real-world survival effectiveness over a longer timeframe. Methods: This retrospective cohort study included patients with ALS across Canada with symptom onset up to three years. Those with a minimum 6-month edaravone exposure between 2017 and 2022 were enrolled in the interventional arm, and those without formed the control arm. The primary outcome of tracheostomy-free survival was compared between the two groups, accounting for age, sex, ALS-disease progression rate, disease duration, pulmonary vital capacity, bulbar ALS-onset, and presence of frontotemporal dementia or C9ORF72 mutation using inverse propensity treatment weights. Results: 182 patients with mean ± SD age 60±11 years were enrolled in the edaravone arm and 860 in the control arm (mean ± SD age 63±12 years). Mean ± SD time from onset to edaravone initiation was 18±10 months. Tracheostomy-free survival will be calculated. Conclusions: This study will provide evidence for edaravone effectiveness on tracheostomy-free survival in patients with ALS.

Background: Saccade and pupil responses are potential neurodegenerative disease biomarkers due to overlap between oculomotor circuitry and disease-affected areas. Instruction-based tasks have previously been examined as biomarker sources, but are arduous for patients with limited cognitive abilities; additionally, few studies have evaluated multiple neurodegenerative pathologies concurrently. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with Alzheimer’s disease (AD), mild cognitive impairment (MCI), amyotrophic lateral sclerosis (ALS), frontotemporal dementia, progressive supranuclear palsy, or Parkinson’s disease (PD). Patients (n=274, age 40-86) and healthy controls (n=101, age 55-86) viewed 10 minutes of frequently changing video clips without instruction while their eyes were tracked. We evaluated differences in saccade and pupil parameters (e.g. saccade frequency and amplitude, pupil size, responses to clip changes) between groups. Results: Preliminary data indicates low-level behavioural alterations in multiple disease cohorts: increased centre bias, lower overall saccade rate and reduced saccade amplitude. After clip changes, patient groups generally demonstrated lower saccade rate but higher microsaccade rate following clip change to varying degrees. Additionally, pupil responses were blunted (AD, MCI, ALS) or exaggerated (PD). Conclusions: This task may generate behavioural biomarkers even in cognitively impaired populations. Future work should explore the possible effects of factors such as medication and disease stage.

Background: What is the number and size of motor units, and axonal excitability profile in the early stages of muscle weakness in ALS compared to controls? Methods: We enrolled ALS patients with APB manual strength testing rated four or four-minus (ALS:4-arm) and four-plus (ALS:4+ arm) and control participants >35 years-old from the University of Toronto, University of Alberta and Universidade Federal de Sao Paulo. Mean±SD, one-way ANOVA and ANCOVA of ALSFRS-R, PUMN Score, MUNIX, MUSIX, and nerve-excitability testing using QTRAC TROND protocol were reported. Results: Twenty-five ALS patients and 63 controls were included. Mean MUNIX was significantly lower (p<0.0001) and MUSIX was significantly higher (p<0.001) in both ALS groups compared to controls. Mean strength-duration time constant in the ALS:4- arm (0.50ms±0.11; p<0.05) and superexcitability in both ALS groups (ALS:4- -29.05%±9.24, ALS:4+ -27.67%±8.03; p<0.05) were relatively increased, supporting axonal hyperexcitability. Conclusions: Significant motor unit loss measured by MUNIX is already present at the earliest detection of muscle weakness in ALS. Increased MUSIX and altered axonal physiology are associated with axonal sprouting and geometry change(1), along with ion channel dysfunction(2). Future trials targeting muscle weakness in ALS should consider the altered neuronal physiology during early disease stages and utilize neurophysiological biomarkers only in normal-to-mildly weak muscles.

Gene-environment interactions (GxE) have been increasingly explored in psychiatry but with low replication rates. Attention-deficit/hyperactivity disorder (ADHD) is a suitable candidate for studying GxE due to its high heritability and well-defined environmental risk factors. Here, we explored GxE using polygenic risk score (PRS) to represent the genetic liability to ADHD (ADHD-PRS) and environmental risk score (ERS) to represent the combined effects of environmental risk factors. We analyzed longitudinal data of 2,046 individuals (6-14 years of age at baseline and 14-23 at the last follow-up) from the Brazilian High-Risk Cohort Study for Psychiatric Disorders. Psychiatric evaluation included the Child Behavior Checklist and the Strength and Difficulties Questionnaire. Statistical analyses were performed using mixed-effects models. We observed statistically significant interactions between ADHD-PRS and ERS, suggesting that environmental and genetic factors act synergistically in the development of ADHD symptoms. These effects were not present for depression or anxiety symptoms. No evidence of GxE correlation was detected. Mechanistically, our findings suggest that environmental stressors modulate the genetic risk for ADHD. Future studies should investigate whether the reduction of environmental risks can prevent the development of symptoms of ADHD, especially in children with a family history of the disorder.

The global and uneven spread of COVID-19, mirrored at the local scale, reveals stark differences along racial and ethnic lines. We respond to the pressing need to understand these divergent outcomes via neighborhood level analysis of mobility and case count information. Using data from Chicago over 2020, we leverage a metapopulation Susceptible-Exposed-Infectious-Removed model to reconstruct and simulate the spread of SARS-CoV-2 at the ZIP Code level. We demonstrate that exposures are mostly contained within one’s own ZIP Code and demographic group. Building on this observation, we illustrate that we can understand epidemic progression using a composite metric combining the volume of mobility and the risk that each trip represents, while separately these factors fail to explain the observed heterogeneity in neighborhood level outcomes. Having established this result, we next uncover how group level differences in these factors give rise to disparities in case rates along racial and ethnic lines. Following this, we ask what-if questions to quantify how segregation impacts COVID-19 case rates via altering mobility patterns. We find that segregation in the mobility network has contributed to inequality in case rates across demographic groups.

Motor unit number index of the upper trapezius (MUNIX-Trapezius) is a candidate biomarker for bulbar lower motor neuron function; however, reliability data is incomplete. To assess MUNIX-Trapezius reliability in controls, we conducted a systematic review, a cross-sectional study (n = 20), and a meta-analysis. We demonstrated a high inter- and intra-rater intraclass correlation (0.86 and 0.94, respectively), indicating that MUNIX-Trapezius is reliable with between-study variability moderated by age and MUNIX technique. With further validation, this measure can serve as a disease monitoring and response biomarker of bulbar function in the therapeutic development for amyotrophic lateral sclerosis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, first notified in China, has spread around the world causing high morbidity and mortality, which is due to factors such as the subversion of the immune response. The aims of the study are to summarise and present the immunopathological relationship of COVID-19 with innate immunity. This is a systematic review conducted by the National Library of Medicine – National Institutes of Health, USA (PUBMED), Latin American and Caribbean Literature on Health Sciences (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE) and Scientific Electronic Library Online (SCIELO) databases with clinical trials, in vitro assays, case-controls, cohort studies, systematic reviews and meta-analyses between February 2020 and July 2021. The version 2 of the Cochrane risk-of-bias tool for RCTs (RoB 2), Joana Briggs Institute (JBI) Critical Appraisal (for the review articles) and the Risk of Bias in Non-randomised Studies of Interventions (ROBINS-I) tools were used to evaluate the quality and the risk of bias of the studies included in this review. The innate immune response through the generation of interferons, alternative pathways and complement system lectins and the joint action of innate immune cells and cytokines and chemokines lead to different clinical outcomes, taking into account the exacerbated inflammatory response and pathogenesis. Then, in addition to interacting as a bridge for adaptive immunity, the innate immune response plays an essential role in primary defense and is one of the starting points for immune evasion by SARS-CoV-2.

Background: Eye movements reveal neurodegenerative disease processes due to overlap between oculomotor circuitry and disease-affected areas. Characterizing oculomotor behaviour in context of cognitive function may enhance disease diagnosis and monitoring. We therefore aimed to quantify cognitive impairment in neurodegenerative disease using saccade behaviour and neuropsychology. Methods: The Ontario Neurodegenerative Disease Research Initiative recruited individuals with neurodegenerative disease: one of Alzheimer’s disease, mild cognitive impairment, amyotrophic lateral sclerosis, frontotemporal dementia, Parkinson’s disease, or cerebrovascular disease. Patients (n=450, age 40-87) and healthy controls (n=149, age 42-87) completed a randomly interleaved pro- and anti-saccade task (IPAST) while their eyes were tracked. We explored the relationships of saccade parameters (e.g. task errors, reaction times) to one another and to cognitive domain-specific neuropsychological test scores (e.g. executive function, memory). Results: Task performance worsened with cognitive impairment across multiple diseases. Subsets of saccade parameters were interrelated and also differentially related to neuropsychology-based cognitive domain scores (e.g. antisaccade errors and reaction time associated with executive function). Conclusions: IPAST detects global cognitive impairment across neurodegenerative diseases. Subsets of parameters associate with one another, suggesting disparate underlying circuitry, and with different cognitive domains. This may have implications for use of IPAST as a cognitive screening tool in neurodegenerative disease.

The objective was to use bibliometric analysis to create an infographic of motor unit number estimation methods over the past 50 years. The original method was published in 1971, but secondary and tertiary waves of research using alternative methods occurred in the early 2000s and a decade later. A metric of influence was used to determine if different methods had clear peaks of use over the past 50 years. While the original method continues to register influence, the MUNIX method introduced in 2004 stands out as the most influential method to estimate the innervation status of skeletal muscles.

This in vitro study evaluated the effect of light curing unit (LCU) type, mouthwashes, and soft drink on chemical degradation of a nanofilled resin composite. Samples (80) were divided into eight groups: halogen LCU, HS—saliva (control); HPT—Pepsi Twist®; HLC—Listerine®; HCP—Colgate Plax®; LED LCU, LS—saliva (control); LPT—Pepsi Twist®; LLC—Listerine®; LCP—Colgate Plax®. The degree of conversion analysis and the measure of the peak area at 2,930 cm−1 (organic matrix) of resin composite were done by Fourier-transform Raman spectroscopy (baseline, after 7 and 14 days). The data were subjected to multifactor analysis of variance (ANOVA) at a 95% confidence followed by Tukey's HSD post-hoc test. The DC ranged from 58.0% (Halogen) to 59.3% (LED) without significance. Differences in the peak area between LCUs were found after 7 days of storage in S and PT. A marked increase in the peak intensity of HLC and LLC groups was found. The soft-start light-activation may influence the chemical degradation of organic matrix in resin composite. Ethanol contained in Listerine® Cool Mint mouthwash had the most significant degradation effect. Raman spectroscopy is shown to be a useful tool to investigate resin composite degradation.