Barriers and opportunities faced by public health practitioners in using public health guidance on COVID-19: a knowledge translation exercise for the eCOVID-19 RecMap.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic prompted the scientific community to collaborate in an unprecedented way, with the rapid and urgent generation and translation of new knowledge about the disease and its' causative agent. Iteratively, and at different levels of government and globally, population level guidance was created, and updated, resulting in the need for a living catalogue of guidelines, the eCOVID-19 Recommendations Map and Gateway to Contextualization (RecMap). This article focuses on the approach that was used to analyse barriers and opportunities associated with using the RecMap in public health in Canada. STUDY DESIGN AND SETTING: A mixed qualitative and quantitative approach data was used to inform this knowledge mobilization project and inform feedback on implementation of the eCOVID-19 RecMap. This approach involved surveying 110 attendees from a public health webinar. Following this webinar, an evidence brief and series of case studies were created and disseminated to 24 Canadian public health practitioners who attended a virtual workshop. This workshop identified barriers and opportunities to improve RecMap use. RESULTS: This study helped to shed light on the needs that public health practitioners have when finding, using, and disseminating public health guidelines. Through the workshop that was conducted, opportunities for public health guidelines can be categorized into four categories: 1) information access, 2) awareness, 3) public health development, and 4) usability. Barriers that were identified can also be categorized into four categories: 1) usability, 2) information maintenance, 3) public health guidance, 4) awareness. CONCLUSION: This work will help to inform the development and organization of future public health guidelines, and the needs that public health practitioners have when engaging with them.

A one-man bilingual cocktail party: linguistic and non-linguistic effects on bilinguals' speech recognition in Mandarin and English.

Multilingual speakers can find speech recognition in everyday environments like restaurants and open-plan offices particularly challenging. In a world where speaking multiple languages is increasingly common, effective clinical and educational interventions will require a better understanding of how factors like multilingual contexts and listeners' language proficiency interact with adverse listening environments. For example, word and phrase recognition is facilitated when competing voices speak different languages. Is this due to a "release from masking" from lower-level acoustic differences between languages and talkers, or higher-level cognitive and linguistic factors? To address this question, we created a "one-man bilingual cocktail party" selective attention task using English and Mandarin speech from one bilingual talker to reduce low-level acoustic cues. In Experiment 1, 58 listeners more accurately recognized English targets when distracting speech was Mandarin compared to English. Bilingual Mandarin-English listeners experienced significantly more interference and intrusions from the Mandarin distractor than did English listeners, exacerbated by challenging target-to-masker ratios. In Experiment 2, 29 Mandarin-English bilingual listeners exhibited linguistic release from masking in both languages. Bilinguals experienced greater release from masking when attending to English, confirming an influence of linguistic knowledge on the "cocktail party" paradigm that is separate from primarily energetic masking effects. Effects of higher-order language processing and expertise emerge only in the most demanding target-to-masker contexts. The "one-man bilingual cocktail party" establishes a useful tool for future investigations and characterization of communication challenges in the large and growing worldwide community of Mandarin-English bilinguals.

Deep homologies in chordate caudal central nervous systems.

Invertebrate chordates, such as the tunicate Ciona, can offer insight into the evolution of the chordate phylum. Anatomical features that are shared between invertebrate chordates and vertebrates may be taken as evidence of their presence in a common chordate ancestor. The central nervous systems of Ciona larvae and vertebrates share a similar anatomy despite the Ciona CNS having ~180 neurons. However, the depth of conservation between the Ciona CNS and those in vertebrates is not resolved. The Ciona caudal CNS, while appearing spinal cord-like, has hitherto been thought to lack motor neurons, bringing into question its homology with the vertebrate spinal cord. We show here that the Ciona larval caudal CNS does, in fact, have functional motor neurons along its length, pointing to the presence of a spinal cord-like structure at the base of the chordates. We extend our analysis of shared CNS anatomy further to explore the Ciona motor ganglion, which has been proposed to be a homolog of the vertebrate hindbrain, spinal cord, or both. We find that a cluster of neurons in the dorsal motor ganglion shares anatomical location, developmental pathway, neural circuit architecture, and gene expression with the vertebrate cerebellum. However, functionally, the Ciona cluster appears to have more in common with vertebrate cerebellum-like structures, insofar as it receives and processes direct sensory input. These findings are consistent with earlier speculation that the cerebellum evolved from a cerebellum-like structure, and suggest that the latter structure was present in the dorsal hindbrain of a common chordate ancestor.

Load and go: Assessing safety outcomes of patients discharged from the emergency department after receiving phenobarbital for alcohol withdrawal.

Objectives: Phenobarbital (PB) is a long-acting GABA A-agonist with favorable pharmacokinetics (long half-life and duration of effect) that allows effective treatment of alcohol withdrawal (AW) after administration of a single loading dose. Current evidence suggests that in the setting of AW, PB administration may be associated with decreased hospital admissions and hospital length of stay. The aim of this study was to evaluate the safety outcomes of AW patients who were treated and discharged from the emergency department (ED) after receiving PB for AW. Methods: This retrospective chart review included a convenience sample of 33 AW patients who presented to four EDs within an 18-month span. Descriptive statistics (frequencies and percentages) were used to describe demographics, distribution of resources and referrals, and the safety outcomes of PB administration for low-risk AW patients. Patients were selected for inclusion in consultation with a medical toxicologist, treated with PB, and discharged from the ED. Electronic medical records were utilized to gather information on the patient cohort. Results: All patients were treated with at least a single loading dose of 5‒10 mg/kg (ideal body weight) of intravenous or per os PB during their ED stay. Only one patient had an unanticipated event after discharge, which was related to driving against advice. Two additional patients had ED revisits for recurrent alcohol use within 72 h, and 16 patients had recurrent alcohol use within 30 days. All 33 patients were provided with resources for linkage to treatment. None required hospital admission. Conclusion: ED PB "load and go" may be a safe, effective AW treatment that could help treat AW, facilitate linkage to specific rehabilitation treatments, and decrease hospital admissions.

Impact of PTSD treatment on postconcussive symptoms in veterans: A comparison of sertraline, prolonged exposure, and their combination.

Many Veterans who served in Iraq and Afghanistan struggle with posttraumatic stress disorder (PTSD) and the effects of traumatic brain injuries (TBI). Some people with a history of TBI report a constellation of somatic, cognitive, and emotional complaints that are often referred to as postconcussive symptoms (PCS). Research suggests these symptoms may not be specific to TBI. This study examined the impact of PTSD treatment on PCS in combat Veterans seeking treatment for PTSD. As part of a larger randomized control trial, 198 Operation Iraqi Freedom, Operation Enduring Freedom, Operation New Dawn (OIF/OEF/OND) Veterans with PTSD received Prolonged Exposure Therapy, sertraline, or the combination. Potential deployment related TBI, PCS, PTSD and depression symptoms were assessed throughout treatment. Linear mixed models were used to predict PCS change over time across the full sample and treatment arms, and the association of change in PTSD and depression symptoms on PCS was also examined. Patterns of change for the full sample and the subsample of those who reported a head injury were examined. Results showed that PCS decreased with treatment. There were no significant differences across treatments. No significant differences were found in the pattern of symptom change based on TBI screening status. Shifts in PCS were predicted by change PTSD and depression. Results suggest that PCS reduced with PTSD treatment in this population and are related to shift in depression and PTSD severity, further supporting that reported PCS symptoms may be better understood as non-specific symptoms.

Trauma-focused therapy retention among military sexual trauma survivors: relationship with veterans' sexual or gender minority identification.

Military servicemembers identifying as sexual and gender minorities (SGM) are at increased risk for military sexual trauma (MST) exposure and Post-traumatic Stress Disorder (PTSD). Although evidence-based treatments can reduce symptoms of PTSD, treatment attrition is concerning. Unfortunately, evaluations of such approaches with veterans identifying as SGM are currently restricted to case studies offering limited information regarding treatment completion. Both historic and current contextual factors related to military and mental health practices may uniquely influence minority veterans' treatment engagement in veteran healthcare settings. We explored associations between SGM identification and treatment of MST-focused therapy completion patterns (finishing the full protocol [FP] or receiving minimally adequate care [MAC; defined as attending eight or more sessions]). Veterans (N = 271, 12.5% SGM) enrolled in individual Prolonged Exposure or Cognitive Processing Therapies at a Midwestern veterans hospital system. Those identifying as SGM were more likely than non-identifying peers to complete FP treatment and, even when attrition occurred, they were retained longer. For MAC, the SGM group was as likely as non-SGM peers to be retained. This research suggests SGM veterans represent a notable minority of those seeking treatment in association with MST and do not appear at greater risk for discontinuation from trauma-focused treatment.

Investigation of genetic determinants of cognitive change in later life.

Cognitive decline is a major health concern and identification of genes that may serve as drug targets to slow decline is important to adequately support an aging population. Whilst genetic studies of cross-sectional cognition have been carried out, cognitive change is less well-understood. Here, using data from the TOMMORROW trial, we investigate genetic associations with cognitive change in a cognitively normal older cohort. We conducted a genome-wide association study of trajectories of repeated cognitive measures (using generalised estimating equation (GEE) modelling) and tested associations with polygenic risk scores (PRS) of potential risk factors. We identified two genetic variants associated with change in attention domain scores, rs534221751 (p = 1 × 10-8 with slope 1) and rs34743896 (p = 5 × 10-10 with slope 2), implicating NCAM2 and CRIPT/ATP6V1E2 genes, respectively. We also found evidence for the association between an education PRS and baseline cognition (at >65 years of age), particularly in the language domain. We demonstrate the feasibility of conducting GWAS of cognitive change using GEE modelling and our results suggest that there may be novel genetic associations for cognitive change that have not previously been associated with cross-sectional cognition. We also show the importance of the education PRS on cognition much later in life. These findings warrant further investigation and demonstrate the potential value of using trial data and trajectory modelling to identify genetic variants associated with cognitive change.

Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank.

OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease with profound unmet need. In patients carrying genetic mutations, elevations in neurofilament light (NfL) have been shown to precede symptom onset, however, the natural history of NfL in general ALS patients is less characterized. METHODS: We performed a secondary analysis of the UK Biobank Pharma Proteomics Project (UKB-PPP), a subset of the UK Biobank, a population-based cohort study in the United Kingdom, to examine plasma NfL levels in 237 participants subsequently diagnosed with ALS. We applied logistic and Cox proportional hazards regression to compare cases to 42,752 population-based and 948 age and sex-matched controls. Genetic information was obtained from exome and genotype array data.Results and Conclusions: We observed that NfL was 1.42-fold higher in cases vs population-based controls. At two to three years pre-diagnosis, NfL levels in patients exceeded the 95th percentile of age and sex-matched controls. A time-to-diagnosis analysis showed that a 2-fold increase in NfL levels was associated with a 3.4-fold risk of diagnosis per year, with NfL being most predictive of case status at two years (AUC = 0.96). Participants with genetic variation that might put them at risk for familial disease (N = 46) did not show a different pattern of association than those without (N = 191). DISCUSSION: Our findings show that NfL is elevated and discriminative of future ALS diagnosis up to two years prior to diagnosis in patients with and without genetic risk variants.

Utility of the Peterborough Public Health COVID-19 rapid antigen test self-report tool: Implications for COVID-19 surveillance.

Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has necessitated novel testing strategies, including the use of rapid antigen tests (RATs). The widespread distribution of RATs to the public prompted Peterborough Public Health to launch a pilot RAT self-report tool to assess its utility in COVID-19 surveillance. The objective of this study is to investigate the utility of RAT using correlations between RAT self-report results and other indicators of COVID-19. Methods: We investigated the association between RAT results, PCR test results and wastewater levels of nmN1N2 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genes (to infer COVID-19 levels) using Pearson's correlation coefficient. Percent positivity and count of positive tests for RATs and polymerase chain reaction (PCR) tests were analyzed. Results: The PCR percent positivity and wastewater were weakly correlated (r=0.33, p=0.022), as were RAT percent positivity and wastewater nmN1N2 levels (r=0.33, p=0.002). The RAT percent positivity and PCR percent positivity were not significantly correlated (r=-0.035, p=0.75). Count of positive RATs and count of positive PCR tests were moderately correlated (r=0.59, p<0.001). Wastewater nmN1N2 levels were not significantly correlated with either count of positive RATs (r=0.019, p=0.864) or count of positive PCR tests (r=0.004, p=0.971). Conclusion: Our results support the use of RAT self-reporting as a low-cost simple adjunctive COVID-19 surveillance tool, and suggest that its utility is greatest when considering an absolute count of positive RATs rather than percent positivity due to reporting bias towards positive tests. These results can help inform COVID-19 surveillance strategies of local public health units and encourage the use of a RAT self-report tool.

Navigating the multiple dimensions of the creativity-mental disorder link: a Convergence Mental Health perspective.

BACKGROUND: This paper discusses a paradox in mental health. It manifests as a relationship between adverse "bad" effects (suffering, clinical costs, loss of productivity) in individuals and populations and advantageous "good" aspects of mental disorders. These beneficial aspects (scientific, artistic and political accomplishments) emanate at the societal level through the frequently unprecedented creativity of people suffering from mental disorders and their relatives. Such gains can contribute to societal innovation and problem-solving. Especially in times of accelerated social-ecological change, approaches are needed that facilitate best-possible mental health care but also recognize creative ideas conducive to beneficial clinical and social-ecological innovations as soon as possible. DISCUSSION: This paper emphasizes the need to account for creativity as a crucial component in evolving mental health systems and societies. It highlights the need for wide-ranging approaches and discusses how research targeting multiple facets (e.g., brain level, cognitive neuroscience, psychiatry, neurology, socio-cultural, economic and other factors) might further our understanding of the creativity-mental disorder link and its importance for innovating mental health systems and societies. CONCLUSION: Our discussion clarifies that considerable research will be needed to obtain a better understanding of how creativity associated with mental disorders may help to create more sustainable societies on a fast-changing planet through innovative ideas. Given the current-state-of-the-art of research and healthcare management, our discussion is currently speculative. However, it provides a basis for how pros and cons might be studied in the future through transdisciplinary research and collaborations across sectors of society.

Sodium nitrite suicide and social media influence.

ABSTRACT: This article addresses the increase in suicide rates in the US, emphasizing the emergence of sodium nitrite ingestion as a method of self-harm, particularly among adolescents and young adults influenced by social media. Given the rising incidence of sodium nitrite-related suicide attempts, healthcare providers must remain vigilant and prepared to respond effectively.

Epigenetic Mechanisms in Obesity: Broadening Our Understanding of the Disease.

Now recognized as more than just the result of overeating or the consumption of poor-quality foods, obesity is understood to be a multifactorial disease, strongly correlated with a variety of environment-gene interactions. In addressing the complex public health issue of obesity, medical practitioners, along with their allied healthcare counterparts, face the challenge of reducing its prevalence by utilizing and sharing with patients the current, yet incomplete, scientific knowledge concerning the disease. While continued research is required to strengthen direct cause-effect relationships, substantial evidence links post-translational modifications such as DNA methylation and histone modifications of several candidate "obesity" genes to the predilection for obesity. Additional evidence supports the influence of maternal diet during the gestational period, individual diet, and other lifestyle and genetic factors in obesity. The purpose of this review is to synthesize the current information concerning epigenetic modifications that appear to support, or result from, the development of obesity. Such mechanisms may serve as therapeutic targets for developing novel prevention and/or treatment strategies for obesity or as epigenetic biomarkers for monitoring recovery.

Plasma proteomic associations with genetics and health in the UK Biobank.

The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validations, insights into proteomic disease signatures, and prediction modelling for various demographic and health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping of 2,923 proteins that identifies 14,287 primary genetic associations, of which 81% are previously undescribed, alongside ancestry-specific pQTL mapping in non-European individuals. The study provides an updated characterization of the genetic architecture of the plasma proteome, contextualized with projected pQTL discovery rates as sample sizes and proteomic assay coverages increase over time. We offer extensive insights into trans pQTLs across multiple biological domains, highlight genetic influences on ligand-receptor interactions and pathway perturbations across a diverse collection of cytokines and complement networks, and illustrate long-range epistatic effects of ABO blood group and FUT2 secretor status on proteins with gastrointestinal tissue-enriched expression. We demonstrate the utility of these data for drug discovery by extending the genetic proxied effects of protein targets, such as PCSK9, on additional endpoints, and disentangle specific genes and proteins perturbed at loci associated with COVID-19 susceptibility. This public-private partnership provides the scientific community with an open-access proteomics resource of considerable breadth and depth to help to elucidate the biological mechanisms underlying proteo-genomic discoveries and accelerate the development of biomarkers, predictive models and therapeutics1.

Post-concussion Return to Shooting Progression for Military Service Members: A Scoping Review and Conceptual Framework.

INTRODUCTION: There are established protocols for staged return to physical activity in sport and military settings following concussion. Currently, there is no evidence-based staged return to shooting protocol in use by the U.S. military despite the unique challenges and stresses shooting places on the vestibular-ocular and cognitive systems often disrupted by a concussion. The primary purpose of this scoping review was to summarize available evidence and current practices on return to shooting post-concussion, with the goal of optimizing an evidence-based return to shooting protocol for military service members. Our secondary aim was to identify individuals who may benefit from a return to shooting progression. MATERIALS AND METHODS: A comprehensive search of PubMed, SPORTDiscus, and Google Scholar was performed from the earliest dates to April 2023. A gray literature (Google) search was also performed. Articles were included if they studied a population with concussion, addressed return to shooting, and were written in English. Articles were excluded if they discussed health conditions other than concussion, focused on non-shooting interventions, did not use human subjects, or were written in a language other than English. RESULTS: Our search strategy yielded 134 articles: 1 article met our inclusion and exclusion criteria, whereas the other 133 articles were rejected. The gray literature search yielded one item. CONCLUSIONS: Based on our results, there is insufficient evidence to inform current practices on return to shooting post-concussion. In the absence of a published return to shooting protocol, we offer recommendations for identifying individuals who may benefit from a return to shooting progression and a revised version of a U.S. Army Special Operations Command Return to Range Progression. This protocol follows a conceptual framework for progression for variables such as environment, weapon type/caliber, and shooter position/movement. Further research is needed on identifying individuals who may benefit from a return to shooting protocol and safely and effectively progressing these individuals through a return to shooting protocol post-concussion.

A single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordate Ciona.

Ciona larvae display a number of behaviors, including negative phototaxis. In negative phototaxis, the larvae first perform short spontaneous rhythmic casting swims. As larvae are cast in a light field, their photoreceptors are directionally shaded by an associated pigment cell, providing a phototactic cue. This then evokes an extended negative taxis swim. We report here that the larval forebrain of Ciona has a previously uncharacterized single slow-oscillating inhibitory neuron (neuron cor-assBVIN78) that projects to the midbrain, where it targets key interneurons of the phototaxis circuit known as the photoreceptor relay neurons. The anatomical location, gene expression, and oscillation of cor-assBVIN78 suggest homology to oscillating neurons of the vertebrate hypothalamus. Ablation of cor-assBVIN78 results in larvae showing extended phototaxis-like swims, even in the absence of phototactic cues. These results indicate that cor-assBVIN78 has a gating activity on phototaxis by projecting temporally oscillating inhibition to the photoreceptor relay neurons. However, in intact larvae, the frequency of cor-assBVIN78 oscillation does not match that of the rhythmic spontaneous swims, indicating that the troughs in oscillations do not themselves initiate swims but rather that cor-assBVIN78 may modulate the phototaxis circuit by filtering out low-level inputs while restricting them temporally to the troughs in inhibition.

Helping children and adolescents who lost a caregiver during the COVID-19 pandemic.

ABSTRACT: Between March 2020 and June of 2021, 140,000 children under 18 in the US lost a caregiver. Due to this sudden loss, their lives have been drastically impacted. This article presents interventions for this population's unique and stressful emotional trauma.

Regulatory imbalance between LRRK2 kinase, PPM1H phosphatase, and ARF6 GTPase disrupts the axonal transport of autophagosomes.

Gain-of-function mutations in the LRRK2 gene cause Parkinson's disease (PD), increasing phosphorylation of RAB GTPases through hyperactive kinase activity. We find that LRRK2-hyperphosphorylated RABs disrupt the axonal transport of autophagosomes by perturbing the coordinated regulation of cytoplasmic dynein and kinesin. In iPSC-derived human neurons, knockin of the strongly hyperactive LRRK2-p.R1441H mutation causes striking impairments in autophagosome transport, inducing frequent directional reversals and pauses. Knockout of the opposing protein phosphatase 1H (PPM1H) phenocopies the effect of hyperactive LRRK2. Overexpression of ADP-ribosylation factor 6 (ARF6), a GTPase that acts as a switch for selective activation of dynein or kinesin, attenuates transport defects in both p.R1441H knockin and PPM1H knockout neurons. Together, these findings support a model where a regulatory imbalance between LRRK2-hyperphosphorylated RABs and ARF6 induces an unproductive "tug-of-war" between dynein and kinesin, disrupting processive autophagosome transport. This disruption may contribute to PD pathogenesis by impairing the essential homeostatic functions of axonal autophagy.

Uncovering the link between the SpnIII restriction modification system and LuxS in Streptococcus pneumoniae meningitis isolates.

Streptococcus pneumoniae is capable of randomly switching their genomic DNA methylation pattern between six distinct bacterial subpopulations (A-F) via recombination of a type 1 restriction-modification locus, spnIII. These pneumococcal subpopulations exhibit phenotypic changes which favor carriage or invasive disease. In particular, the spnIIIB allele has been associated with increased nasopharyngeal carriage and the downregulation of the luxS gene. The LuxS/AI-2 QS system represent a universal language for bacteria and has been linked to virulence and biofilm formation in S. pneumoniae. In this work, we have explored the link between spnIII alleles, the luxS gene and virulence in two clinical pneumococcal isolates from the blood and cerebrospinal fluid (CSF) of one pediatric meningitis patient. The blood and CSF strains showed different virulence profiles in mice. Analysis of the spnIII system of these strains recovered from the murine nasopharynx showed that the system switched to different alleles commensurate with the initial source of the isolate. Of note, the blood strain showed high expression of spnIIIB allele, previously linked with less LuxS protein production. Importantly, strains with deleted luxS displayed different phenotypic profiles compared to the wildtype, but similar to the strains recovered from the nasopharynx of infected mice. This study used clinically relevant S. pneumoniae strains to demonstrate that the regulatory network between luxS and the type 1 restriction-modification system play a key role in infections and may support different adaptation to specific host niches.

A single oscillating proto-hypothalamic neuron gates taxis behavior in the primitive chordate Ciona.

Ciona larvae display a number of behaviors, including negative phototaxis. In negative phototaxis, the larvae first perform short spontaneous rhythmic casting swims. As larvae cast in a light field, their photoreceptors are directionally shaded by an associated pigment cell, providing a phototactic cue. This then evokes an extended negative taxis swim. We report here that the larval forebrain of Ciona has a previously uncharacterized single slow-oscillating inhibitory neuron (neuron cor-assBVIN78 ) that projects to the midbrain, where it targets key interneurons of the phototaxis circuit known as the photoreceptor relay neurons . The anatomical location, gene expression and oscillation of cor-assBVIN78 suggest homology to oscillating neurons of the vertebrate hypothalamus. Ablation of cor-assBVIN78 results in larvae showing extended phototaxis-like swims, but which occur in the absence of phototactic cues. These results indicate that cor-assBVIN78 has a gating activity on phototaxis by projecting temporally-oscillating inhibition to the photoreceptor relay neurons. However, in intact larvae the frequency of cor-assBVIN78 oscillation does not match that of the rhythmic spontaneous swims, indicating that the troughs in oscillations do not themselves initiate swims, but rather that cor-assBVIN78 may modulate the phototaxis circuit by filtering out low level inputs while restricting them temporally to the troughs in inhibition.