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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.

BackgroundSarcopenia, visceral obesity (VO), and reduced muscle radiodensity (myosteatosis) are suggested risk factors for postoperative morbidity in colorectal cancer (CRC), but usually are not concurrently assessed. Published thresholds used to define these features are not CRC-specific and are defined in relation to mortality, not postoperative outcomes. This study aimed to evaluate body composition in relation to length of hospital stay (LOS) and postoperative outcomes.MethodsPre-surgical computed tomography (CT) images were assessed for total area and radiodensity of skeletal muscle and visceral adipose tissue in a pooled Canadian and UK cohort (n = 2100). Sex- and age-specific values for these features were calculated. For 1139 of 2100 patients, LOS data were available, and sex- and age-specific thresholds for sarcopenia, myosteatosis, and VO were defined on the basis of LOS. Association of CT-defined features with LOS and readmissions was explored using negative binomial and logistic regression models, respectively.ResultsIn the multivariable analysis, the predictors of LOS (P < 0.001) were age, surgical approach, major complications (incidence rate ratio [IRR] 2.42; 95% confidence interval [CI] 2.18–2.68), study cohort, and three body composition profiles characterized by myosteatosis combined with either sarcopenia (IRR, 1.27; 95% CI 1.12–1.43) or VO (IRR, 1.25; 95% CI 1.10–1.42), and myosteatosis combined with both sarcopenia and VO (IRR, 1.58; 95% CI 1.29–1.93). In the multivariable analysis, risk of readmission was associated with VO alone (odds ratio [OR] 2.66; 95% CI 1.18–6.00); P = 0.018), VO combined with myosteatosis (OR, 2.72; 95% CI 1.36–5.46; P = 0.005), or VO combined with myosteatosis and sarcopenia (OR, 2.98; 95% CI 1.06–5.46; P = 0.038). Importantly, the effect of body composition profiles on LOS and readmission was independent of major complications.ConclusionThe findings showed that CT-defined multidimensional body habitus is independently associated with LOS and hospital readmission.

The roles of R-loops and RNA modifications in homologous recombination (HR) and other DNA double-stranded break (DSB) repair pathways remain poorly understood. Here, we find that DNA damage-induced RNA methyl-5-cytosine (m5C) modification in R-loops plays a crucial role to regulate PARP1-mediated poly ADP-ribosylation (PARylation) and the choice of DSB repair pathways at sites of R-loops. Through bisulfite sequencing, we discover that the methyltransferase TRDMT1 preferentially generates m5C after DNA damage in R-loops across the genome. In the absence of m5C, R-loops activate PARP1-mediated PARylation both in vitro and in cells. Concurrently, m5C promotes transcription-coupled HR (TC-HR) while suppressing PARP1-dependent alternative non-homologous end joining (Alt-NHEJ), favoring TC-HR over Alt-NHEJ in transcribed regions as the preferred repair pathway. Importantly, simultaneous disruption of both TC-HR and Alt-NHEJ with TRDMT1 and PARP or Polymerase θ inhibitors prevents alternative DSB repair and exhibits synergistic cytotoxic effects on cancer cells, suggesting an effective strategy to exploit genomic instability in cancer therapy. Here the authors show that DNA damage induced RNA m5C in R-loops competes with PARP1- mediated PARylation in transcribed genomes to promote cell survival which could be targeted be in cancer therapy.

Emerging evidence suggests that syndromic surveillance systems can predict outbreaks of COVID-19 with high spatial and temporal resolution.1–3 These methods can be used as early warning systems to guide regional decisions about public health policy. Tools include passive methods (eg, tracking health-care encounters) and more active participatory surveillance, whereby individuals self-report symptoms by telephone or internet.2–4 It is unknown whether circulating seasonal respiratory viruses affect the performance of surveillance tools for COVID-19, although symptomatic overlap makes it a theoretical concern.5 We investigated the role of test positivity for non-SARS-CoV-2 respiratory viruses on two independent COVID-19 syndromic surveillance systems in Ontario, Canada. COVID-19-like illness was defined according to the US Centers for Disease Control and Prevention surveillance case definition for COVID-19.6 The Acute Care Enhanced Surveillance system uses validated machine learning algorithms to categorise visits to emergency departments into clinical syndromes.7 See appendix (pp 1–2) for a full description of data sources and syndromic definitions.

Limitations in laboratory diagnostic capacity impact population surveillance of COVID-19. It is currently unknown whether participatory surveillance tools for COVID-19 correspond to government-reported case trends longitudinally and if it can be used as an adjunct to laboratory testing. The primary objective of this study was to determine whether self-reported COVID-19-like illness reflected laboratory-confirmed COVID-19 case trends in Ontario Canada. We retrospectively analyzed longitudinal self-reported symptoms data collected using an online tool-Outbreaks Near Me (ONM)-from April 20th, 2020, to March 7th, 2021 in Ontario, Canada. We measured the correlation between COVID-like illness among respondents and the weekly number of PCR-confirmed COVID-19 cases and provincial test positivity. We explored contemporaneous changes in other respiratory viruses, as well as the demographic characteristics of respondents to provide context for our findings. Between 3,849-11,185 individuals responded to the symptom survey each week. No correlations were seen been self-reported CLI and either cases or test positivity. Strong positive correlations were seen between CLI and both cases and test positivity before a previously documented rise in rhinovirus/enterovirus in fall 2020. Compared to participatory surveillance respondents, a higher proportion of COVID-19 cases in Ontario consistently came from low-income, racialized and immigrant areas of the province- these groups were less well represented among survey respondents. Although digital surveillance systems are low-cost tools that have been useful to signal the onset of viral outbreaks, in this longitudinal comparison of self-reported COVID-like illness to Ontario COVID-19 case data we did not find this to be the case. Seasonal respiratory virus transmission and population coverage may explain this discrepancy.

Use of cross-sectional imaging to identify whole-body lean soft-tissue mass has recently emerged as an attractive prognostic factor for chemotherapy toxicities. Beyond that, there is increasing interest in use of lean soft-tissue mass as a more accurate method for dosing chemotherapy, as compared to body surface area. In this review, we summarize the current evidence that supports interactions between skeletal muscle and chemotherapy, the role of lean soft tissue in predicting chemotherapy toxicities and potential use of an alternate method of chemotherapeutic dosing, all based on quantification of skeletal muscle mass by computed tomography.

Background Sarcopenia at time of diagnosis predicts worse survival outcomes. It is currently unknown how changes in muscle mass over time interact with sarcopenia in colorectal patients treated with curative intent. Objectives of this study were to quantify sarcopenia and skeletal muscle loss from time of diagnosis to end of surveillance and determine its effect on survival outcomes after completion of 2 years of surveillance. Methods Retrospective cohort study of stage I–III colorectal cancer patients from 2007–2009, who underwent resection and had preoperative and 2-year surveillance computed tomography scans, without recurrence during that time. Body composition analysis was done at both time points to determine lumbar skeletal muscle index, radiodensity and adiposity. Change over time was standardized as a percentage per year. Cox proportional hazard regression modeling was used for survival analysis. Results Of 667 patients included, median survival from surgery was 7.96 years, with 75 recurrences occurring after 2 years. On average patients lost muscle mass (−0.415%/year; CI −0.789, −0.042) and radiodensity (−5.76 HU/year; CI −6.74, −4.80), but gained total adipose tissue (7.06%/year; CI 4.34, 9.79). Patients with sarcopenia at diagnosis (HR 1.80; CI 1.13, 2.85) or muscle loss over time (HR 1.55; CI 1.01, 2.37) had worse overall survival, with significantly worse joint effect (HR 2.73; CI 1.32, 5.65). Conclusions Sarcopenia at diagnosis combined with ongoing skeletal muscle loss over time resulted in significantly worse survival. Patients with these features who are recurrence-free at 2 years are more likely to have a non-colorectal cancer cause of death.

Background During the first wave of COVID-19 there was little evidence to guide appropriate child and family programs and policy supports. Methods We compared policies and programs implemented to support early child health and well-being during the first wave of COVID-19 in Australia, Canada, the Netherlands, Singapore, the UK, and the USA. Program and policy themes were focused on prenatal care, well-baby visits and immunization schedules, financial supports, domestic violence and housing, childcare supports, child protective services, and food security. Results Significant heterogeneity in implementation of OECD-recommended policy responses was found with all of the included countries implementing some of these policies, but no country implementing supports in all of the potential areas. Conclusions This analysis gives insight into initial government reactions to support children and families, and opportunities for governments to implement further supportive programs and policies during the current pandemic and future emergencies.

Transitions of cancer cells between distinct cell states, which are typically driven by transcription reprogramming, fuel tumor plasticity, metastasis, and therapeutic resistance. Whether the transitions between cell states can be therapeutically targeted remains unknown. Here, using the epithelial-to-mesenchymal transition (EMT) as a model, we show that the transcription reprogramming during a cell-state transition induces genomic instability through R-loops and transcription-replication conflicts, and the cell-state transition cannot occur without the ATR kinase, a key regulator of the replication stress response. ATR inhibition during EMT not only increases transcription- and replication-dependent genomic instability but also disrupts transcription reprogramming. Unexpectedly, ATR inhibition elevates R-loop-associated DNA damage at the SNAI1 gene, a key driver of the transcription reprogramming during EMT, triggering ATM- and Polycomb-mediated transcription repression of SNAI1. Beyond SNAI1, ATR also suppresses R-loops and antagonizes repressive chromatin at a subset of EMT genes. Importantly, inhibition of ATR in tumors undergoing EMT reduces tumor growth and metastasis, suggesting that ATR inhibition eliminates cancer cells in transition. Thus, during EMT, ATR not only protects genome integrity but also enables transcription reprogramming, revealing that ATR is a safeguard of cell-state transitions and a target to suppress tumor plasticity.

BackgroundMeasurement of body composition by computed tomography (CT) is an advancing field. Sarcopenia, myosteatosis, and visceral obesity (VO) have been identified as predictive of survival in colorectal cancer (CRC). We performed a systematic review of contemporary studies to characterize this association and highlight methodological inconsistencies.MethodsMEDLINE and PubMed were queried for articles published from January 2000 on, with populations of resectable CRC and with CT-measured body composition and survival data. The study quality was assessed by two independent reviewers using the Newcastle–Ottawa Scale.ResultsTwenty studies met inclusion criteria, with a total of 8895 patients. Only two of the studies scored as high quality and nine as moderate quality. The remaining nine studies scored as low quality. Ten studies considered sarcopenia and 12 considered visceral obesity (VO). Cutoff points to define sarcopenia, myosteatosis, and VO were identified by optimal stratification, quartiles, or median values. The prevalence of sarcopenia varied from 15 to 60%, which based on study population and cutoff value used. Sarcopenia was associated with worse overall and disease-free survival in eight of the included studies. Myosteatosis was considered in three studies with a prevalence of 19–78%. It was significantly predictive of worse overall and disease-free survival in all three studies. VO had a prevalence of 14–70% and was inconsistently predictive of survival outcomes.ConclusionsThere is a lack of methodological consistency within the currently published literature. Despite this, sarcopenia and myosteatosis, but not VO, are consistently associated with worse survival outcomes, when population and cancer-specific cutoffs are utilized.