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Background This study presents the prevalence of burnout among the Canadian public health workforce after three years of the COVID-19 pandemic and its association with work-related factors. Methods Data were collected using an online survey distributed through Canadian public health associations and professional networks between November 2022 and January 2023. Burnout was measured using a modified version of the Oldenburg Burnout Inventory (OLBI). Logistic regressions were used to model the relationship between burnout and work-related factors including years of work experience, redeployment to pandemic response, workplace safety and supports, and harassment. Burnout and the intention to leave or retire as a result of the COVID-19 pandemic was explored using multinomial logistic regressions. Results In 2,079 participants who completed the OLBI, the prevalence of burnout was 78.7%. Additionally, 49.1% of participants reported being harassed because of their work during the pandemic. Burnout was positively associated with years of work experience, redeployment to the pandemic response, being harassed during the pandemic, feeling unsafe in the workplace and not being offered workplace supports. Furthermore, burnout was associated with greater odds of intending to leave public health or retire earlier than anticipated. Conclusion The high levels of burnout among our large sample of Canadian public health workers and its association with work-related factors suggest that public health organizations should consider interventions that mitigate burnout and promote recovery.

The diets of the mangrove crabs, Metopograpsus frontalis Miers and Perisesarma bidens de Haan, were investigated monthly for 13 months at two Hong Kong mangroves, to examine possible spatial and temporal influences on their feeding ecology. In both species, a higher degree of gut fullness was observed in summer (May-September) than in winter, suggesting a reduction in winter foraging activity. M. frontalis was omnivorous, with animal and plant materials and inorganic sediments being the major food items. P. bidens was detritivorous, with plant materials and inorganic sediment dominating the gut contents. M. frontalis is, therefore, an opportunistic feeder, whilst P. bidens, like many other members of the Sesarmidae, is a detritivore. Some degree of seasonal variation was shown in the diet of M. frontalis (with more algal material in winter) and P. bidens (with more sediments in summer), but diets were similar between sexes in both species. The dietary pattern of M. frontalis also varied between sites. The diets of the crabs, therefore, appear to be a result of the interplay between the seasonal, physical climate and biological factors, especially food availability and the crabs' ecology. Results suggest that the predatory role of Metopograpsus, which has been poorly studied, is potentially important to estuarine food webs; whilst the trophic importance of sesarmid crabs, such as Perisesarma, especially in mangrove outwelling, should be critically re-evaluated.

Background The Canadian drug supply has significantly increased in toxicity over the past few years, resulting in the worsening of the overdose crisis. A key initiative implemented during this crisis has been data monitoring and reporting of substance use-related harms (SRH). This literature review aims to: (1) identify strategies used for the meaningful engagement of people who use drugs (PWUD) in local, provincial, and national SRH data system planning, reporting, and action and (2) describe data monitoring and reporting strategies and common indicators of SRH within those systems. Methods We searched three academic and five gray literature databases for relevant literature published between 2012 and 2022. Team members who identify as PWUD and a librarian at Public Health Ontario developed search strings collaboratively. Two reviewers screened all search results and applied the eligibility criteria. We used Microsoft Excel for data management. Results Twenty-two articles met our eligibility criteria (peer-reviewed n  = 10 and gray literature reports n  = 12); most used qualitative methods and focused on the Canadian context ( n  = 20). There were few examples of PWUD engaged as authors of reports on SRH monitoring. Among information systems involving PWUD, we found two main strategies: (1) community-based strategies (e.g., word of mouth, through drug sellers, and through satellite workers) and (2) public health-based data monitoring and communication strategies (e.g., communicating drug quality and alerts to PWUD). Substance use-related mortality, hospitalizations, and emergency department visits were the indicators most commonly used in systems of SRH reporting that engaged PWUD. Conclusion This review demonstrates limited engagement of PWUD and silos of activity in existing SRH data monitoring and reporting strategies. Future work is needed to better engage PWUD in these processes in an equitable manner. Building SRH monitoring systems in partnership with PWUD may increase the potential impact of these systems to reduce harms in the community.

Background Quantitative methods of Fluorodeoxyglucose Positron Emission Tomography (FDG‐PET) interpretation, including the percent change in FDG uptake from baseline (ΔSUV), are under investigation in lymphoma to overcome challenges associated with visual scoring systems (VSS) such as the Deauville 5‐point scale (5‐PS). Methods In CALGB 50303, patients with DLBCL received frontline R‐CHOP or DA‐EPOCH‐R, and although there were no significant associations between interim PET responses assessed centrally after cycle 2 (iPET) using 5‐PS with progression‐free survival (PFS) or overall survival (OS), there were significant associations between central determinations of iPET ∆SUV with PFS/OS. In this patient cohort, we retrospectively compared local vs central iPET readings and evaluated associations between local imaging data and survival outcomes. Results Agreement between local and central review was moderate (kappa = 0.53) for VSS and high (kappa = 0.81) for ∆SUV categories (<66% vs. ≥66%). ∆SUV ≥66% at iPET was significantly associated with PFS (p = 0.03) and OS (p = 0.002), but VSS was not. Associations with PFS/OS when applying local review vs central review were comparable. Conclusions These data suggest that local PET interpretation for response determination may be acceptable in clinical trials. Our findings also highlight limitations of VSS and call for incorporation of more objective measures of response assessment in clinical trials. In this retrospective analysis of CALGB 50303 study, Torka et al. found that associations with PFS and OS when applying local review versus central review of interim PET (iPET) were comparable? SUV = 66% at iPET was associated with PFS and OS, but visual scoring systems (VSS) were not, highlighting the limitations of VSS.

This paper contrasts responses in the soleus muscle of normal human subjects to two major inputs: the tibial nerve (TN) and the corticospinal tract. Paired transcranial magnetic stimulation (TMS) of the motor cortex at intervals of 10–25 ms strongly facilitated the motor evoked potential (MEP) produced by the second stimulus. In contrast, paired TN stimulation produced a depression of the reflex response to the second stimulus. Direct activation of the pyramidal tract did not facilitate a second response, suggesting that the MEP facilitation observed using paired TMS occurred in the cortex. A TN stimulus also depressed a subsequent MEP. Since the TN stimulus depressed both inputs, the mechanism is probably post-synaptic, such as afterhyperpolarization of motor neurons. Presynaptic mechanisms, such as homosynaptic depression, would only affect the pathway used as a conditioning stimulus. When TN and TMS pulses were paired, the largest facilitation occurred when TMS preceded TN by about 5 ms, which is optimal for summation of the two pathways at the level of the spinal motor neurons. A later, smaller facilitation occurred when a single TN stimulus preceded TMS by 50–60 ms, an interval that allows enough time for the sensory afferent input to reach the sensory cortex and be relayed to the motor cortex. Other work indicates that repetitively pairing nerve stimuli and TMS at these intervals, known as paired associative stimulation, produces long-term increases in the MEP and may be useful in strengthening residual pathways after damage to the central nervous system.

Background Systemic inflammation induces neuroimmune activation, ultimately leading to sickness (e.g., fever, anorexia, motor impairments, exploratory deficits, and social withdrawal). In this study, we evaluated the role of protein kinase R (PKR), a serine-threonine kinase that can control systemic inflammation, on neuroimmune responses and sickness. Methods Wild-type (WT) PKR+/+ mice and PKR−/− mice were subcutaneously injected with live Escherichia coli ( E. coli ) or vehicle. Food consumption, rotarod test performance, burrowing, open field activity, object investigation, and social interaction were monitored. Plasma TNF-α and corticosterone were measured by ELISA. The percentage of neutrophils in blood was deduced from blood smears. Inflammatory gene expression (IL-1β, TNF-α, IL-6, cyclooxygenase (COX)-2, iNOS) in the liver and the brain (hypothalamus and hippocampus) were quantified by real-time PCR. Blood and lavage fluid (injection site) were collected for microbiological plate count and for real-time PCR of bacterial 16S ribosomal DNA (rDNA). Corticotrophin-releasing hormone (CRH) expression in the hypothalamus was also determined by real-time PCR. Results Deficiency of PKR diminished peripheral inflammatory responses following E. coli challenge. However, while the core components of sickness (anorexia and motor impairments) were similar between both strains of mice, the behavioral components of sickness (reduced burrowing, exploratory activity deficits, and social withdrawal) were only observable in PKR−/− mice but not in WT mice. Such alteration of behavioral components was unlikely to be caused by exaggerated neuroimmune activation, by an impaired host defense to the infection, or due to a dysregulated corticosterone response, because both strains of mice displayed similar neuroimmune responses, bacterial titers, and plasma corticosterone profiles throughout the course of infection. Nevertheless, the induction of hypothalamic corticotrophin-releasing hormone (CRH) by E. coli was delayed in PKR−/− mice relative to WT mice, suggesting that PKR deficiency may postpone the CRH response during systemic inflammation. Conclusions Taken together, our findings show that (1) loss of PKR could alter E. coli -induced sickness behaviors and (2) this was unlikely to be due to exacerbated neuroimmune activation, (3) elevated bacterial load, or (4) dysregulation in the corticosterone response. Further studies can address the role of PKR in the CRH response together with its consequence on sickness.

Tandem mass spectrometry has been used to compare gas-phase and solution binding of three small-molecule inhibitors to the wild type and three mutant forms of the catalytic domain of Cex, an enzyme that hydrolyses xylan and xylo-oligosaccharides. The inhibitors, xylobiosyl-deoxynojirimycin, xylobiosyl-isofagomine lactam, and xylobiosyl-isofagomine consist of a common distal xylose linked to different proximal aza-sugars. The three mutant forms of the enzyme contain the substitutions Asn44Ala, Gln87Met, and Gln87Tyr that alter the binding interactions between Cex and the distal sugar of each inhibitor. An electrospray ionization (ESI) triple quadrupole MS/MS system is used to measure the internal energies, Δ E int , that must be added to gas-phase ions to cause dissociation of the noncovalent enzyme-inhibitor complexes. Collision cross sections of ions of the apo-enzyme and enzyme-inhibitor complexes, which are required for the calculations of Δ E int , have also been measured. The results show that, in the gas phase, enzyme-inhibitor complexes have more compact, folded conformations than the corresponding apo-enzyme ions. With the mutant enzymes, the effects of substituting a single residue can be detected. The energies required to dissociate the gas-phase complexes follow the same trend as the values of Δ G 0 for dissociation of the complexes in solution. This trend is observed both with different inhibitors, which probe binding to the proximal sugar, and with mutants of Cex, which probe binding to the distal sugar. Thus the gas-phase complexes appear to retain much of their solution binding characteristics.

We observed the alert responses of Sciurus carolinensis (Eastern Gray Squirrel) to two different approach stimuli (human only and human with a leashed dog) in two suburban habitats differing in the level of human activity. Alert distance in the habitat with higher levels of human activity was significantly shorter than the alert distance in the habitat with lower levels of human activity. Overall, the alert distance did not differ between the approach by a human alone and the approach by a human with a dog; however, in the high human activity sites (but not the low human activity sites), the presence of the dog increased alert distance in the squirrels. In addition, squirrels tended to initially respond by running more in the high human activity sites, but the presence of the dog increased the number of squirrels whose initial responses were to not run. Our results suggest that Eastern Gray Squirrel antipredator behavior, at least in response to humans and human-associated animals, is influenced by the level of human activity in the surrounding habitat.

Blast injury to the brain is one of the major causes of death and can also significantly affect cognition and physical and psychological skills in survivors of blast. The complex mechanisms via which blast injury causes impairment of cognition and other symptoms are poorly understood. In this study, we investigated the effects of varying degrees of primary blast overpressure (BOP; 80 and 200 kPa) on the pathophysiological and magnetic resonance imaging (MRI) changes and neurocognitive performance as assessed by the monkey Cambridge Neuropsychological Test Automated Battery (mCANTAB) in non-human primates (NHP). The study aimed to examine the effects of neurobehavioral and histopathological changes in NHP. MRI and histopathology revealed ultrastructural changes in the brain, notably in the Purkinje neurons in the cerebellum and pyramidal neurons in the hippocampus, which were most vulnerable to the blast. The results correlated well with the behavioral changes and changes in motor coordination and working memory of the affected monkeys. In addition, there was white matter damage affecting myelinated axons, astrocytic hypertrophy, and increased aquaporin-4 (AQP-4) expression in astrocytes, suggesting cerebral edema. Increased apoptosis appeared to involve astrocytes and oligodendrocytes in the animals following blast exposure. The small sample size could have contributed to the non-significant outcome in cognitive performance post-blast and limited quantitative analyses. Nevertheless, the study has provided initial descriptive changes for establishing a primary BOP threshold for brain injury to serve as a useful platform for future investigations that aim to estimate brain injury potential and set safe limits of exposure.

The development of symptoms in patients with epiretinal membranes (ERMs) often corresponds with the accumulation of interstitial fluid in the retina [i.e., the development of macular edema, (ME)]. To explore the potential value of pharmacologic therapeutic options to treat ME in patients with ERMs, we examine here the expression of vasoactive and inflammatory mediators in the vitreous of patients with idiopathic ERMs. We observed that vitreous concentrations of classic vasoactive factors (e.g., vascular endothelial growth factor) were similar in ERM patients with ME compared to controls. Using an array assessing the expression of 102 inflammatory cytokines we similarly did not observe a marked difference in cytokine expression in the vitreous of most ERM patients with ME compared to control patients. While the array data did implicate a group of inflammatory cytokines that were elevated in a subset of ERM patients who had severe ME (central subfield thickness ≥450 μm on spectral domain optical coherence tomography), expression of 3 of these inflammatory cytokines, all previously implicated in the promotion of ME in ischemic retinal disease, were not elevated by quantitative enzyme-linked immunosorbent assay. We conclude that therapies modulating vasoactive mediators or inflammatory cytokines may not affect ME in ERM patients.