p38-γ–dependent gene silencing restricts entry into the myogenic differentiation program

The regenerative capacity of muscle is regulated by p38-γ, which phosphorylates MyoD and leads to formation of a complex that represses myogenin transcription

Zac1, a zinc finger transcription factor, is a direct Pax7 target gene in post-natal myogenesis

Pax7 plays an essential role in the commitment, survival and expansion of myogenic progenitors during postnatal muscle growth and regeneration. Recently, our genome-wide expression study in myoblasts identified Myf5 and Zac1 (PlagL1; encoding a zinc-finger transcription factor) as transcripts regulated by Pax7. Zac1 has been previously identified as a tumour suppressor showing anti-proliferative properties through regulation of apoptosis and cell cycle arrest. Zac1 expression paralleled that of Pax7 during myogenic progression, with both genes being expressed at high levels in proliferating primary myoblasts but being rapidly down-regulated during cell-cycle arrest and terminal differentiation. Genome wide protein-DNA interaction profiling and chromatin immunoprecipitation assays have identified a region bound by Pax7 at +11 kb from the Zac1 transcriptional start. This region contains a novel Pax7 consensus sequence that is conserved across species and is functionally activated by the Pax7/FKHR fusion protein. Together these data support the assertion that Zac1 is directly activated by Pax7. Regeneration assays conducted in Zac1-null mice indicate a critical role for Zac1 in mediating efficient regenerative myogenesis. Further elucidation of the functional regulation of Zac1 by Pax7 will provide important insight into the mechanism by which Pax7 defines the cellular phenotype of myogenic progenitors

“White Cord Syndrome” of Acute Tetraplegia after Anterior Cervical Decompression and Fusion for Chronic Spinal Cord Compression: A Case Report

Paralysis is the most feared postoperative complication of ACDF and occurs most often due to an epidural hematoma. In the absence of a clear etiology, inadequate decompression or vascular insult such as ischemia/reperfusion injury are the usual suspects. Herewith we report a case of complete loss of somatosensory evoked potentials (SSEPs) during elective ACDF at C4-5 and C5-6 followed by postoperative C6 incomplete tetraplegia without any discernible technical cause. A postoperative MRI demonstrated a large area of high signal changes on T2-weighted MRI intrinsic to the cord “white cord syndrome” but no residual compression. This was considered consistent with spinal cord gliosis with possible acute edema. The acute decompression of the herniated disc resulted in cord expansion and rush-in reperfusion. We postulate that this may have led to disruption in the blood brain barrier (BBB) and triggered a cascade of reperfusion injuries resulting in acute neurologic dysfunction. At 16 months postoperatively our patient is recovering slowly and is now a Nurick Grade 4

Postoperative Cervical Haematoma Complicated by Ipsilateral Carotid Thrombosis and Aphasia after Anterior Cervical Fusion: A Case Report

Hematoma alone is the most common vascular complication reported after anterior cervical decompression and fusion (ACDF). We present this case to report the occurrence of postoperative cervical hematoma complicated by ipsilateral carotid thrombosis and aphasia after an uncomplicated C4–6 ACDF. This is a case of a 65-year-old woman who underwent revision fusions of the C4-5 and C6-7 levels complicated by postoperative cervical hematoma and carotid thrombosis. The patient's history, clinical examination, imaging findings, and treatment are reported. The revision fusions were performed and deemed routine. Approximately eight hours later 200 mL of blood was evacuated from a postoperative cervical hematoma. The patient became unresponsive and disoriented a few hours after evacuating the hematoma. Computed tomography and magnetic resonance imaging of the brain were normal, but magnetic resonance angiography demonstrated total occlusion of the left carotid artery. Thrombectomy was performed and the patient was discharged without residual deficits. At the latest followup she is fully functional and asymptomatic in her neck. We suggest, after evacuating a cervical hematoma, an evaluation of the carotids be made with MRA or cerebral angiography, as this may demonstrate a clot before the patient develops symptoms

Understanding the mental health and intention to leave of the public health workforce in Canada during the COVID-19 pandemic: A cross-sectional study

Abstract Background There is limited evidence about the mental health and intention to leave of the public health workforce in Canada during the COVID-19 pandemic. The objectives of this study were to determine the prevalence of burnout, symptoms of anxiety and depression, and intention to leave among the Canadian public health workforce, and associations with individual and workplace factors. Methods A cross-sectional study was conducted using data collected by a Canada-wide survey from November 2022 to January 2023, where participants reported sociodemographic and workplace factors. Mental health outcomes were measured using validated tools including the Oldenburg Burnout Inventory, the 7-item Generalized Anxiety Disorder scale, and the 2-item Patient Health Questionnaire to measure symptoms of depression. Participants were asked to report if they intended to leave their position in public health. Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) for the associations between explanatory variables such as sociodemographic, workplace factors, and outcomes of mental health, and intention to leave public health. Results Among the 671 participants, the prevalence of burnout, and symptoms of depression and anxiety in the two weeks prior were 64%, 26%, and 22% respectively. 33% of participants reported they were intending to leave their public health position in the coming year. Across all outcomes, sociodemographic factors were largely not associated with mental health and intention to leave. However, an exception to this was that those with 16–20 years of work experience had higher odds of burnout (aOR = 2.16; 95% CI = 1.12–4.18) compared to those with ≤ 5 years of work experience. Many workplace factors were associated with mental health outcomes and intention to leave public health. Those who felt bullied, threatened, or harassed because of work had increased odds of depressive symptoms (aOR = 1.85; 95% CI = 1.28–2.68), burnout (aOR = 1.61; 95% CI = 1.16–2.23), and intention to leave (aOR = 1.64; 95% CI = 1.13–2.37). Conclusions During the COVID-19 pandemic, some of the public health workforce experienced negative impacts on their mental health. 33% of the sample indicated an intention to leave their role, which has the potential to exacerbate pre-existing challenges in workforce retention. Study findings create an impetus for policy and practice changes to mitigate risks to mental health and attrition to create safe and healthy working environments for public health workers during public health crises

Context matters: the experience of 14 research teams in systematically reporting contextual factors important for practice change.

PURPOSE: We aimed to advance the internal and external validity of research by sharing our empirical experience and recommendations for systematically reporting contextual factors. METHODS: Fourteen teams conducting research on primary care practice transformation retrospectively considered contextual factors important to interpreting their findings (internal validity) and transporting or reinventing their findings in other settings/situations (external validity). Each team provided a table or list of important contextual factors and interpretive text included as appendices to the articles in this supplement. Team members identified the most important contextual factors for their studies. We grouped the findings thematically and developed recommendations for reporting context. RESULTS: The most important contextual factors sorted into 5 domains: (1) the practice setting, (2) the larger organization, (3) the external environment, (4) implementation pathway, and (5) the motivation for implementation. To understand context, investigators recommend (1) engaging diverse perspectives and data sources, (2) considering multiple levels, (3) evaluating history and evolution over time, (4) looking at formal and informal systems and culture, and (5) assessing the (often nonlinear) interactions between contextual factors and both the process and outcome of studies. We include a template with tabular and interpretive elements to help study teams engage research participants in reporting relevant context. CONCLUSIONS: These findings demonstrate the feasibility and potential utility of identifying and reporting contextual factors. Involving diverse stakeholders in assessing context at multiple stages of the research process, examining their association with outcomes, and consistently reporting critical contextual factors are important challenges for a field interested in improving the internal and external validity and impact of health care research