The transcription factor MEF2 directs developmental visually driven functional and structural metaplasticity.

Natural sensory input shapes both structure and function of developing neurons, but how early experience-driven morphological and physiological plasticity are interrelated remains unclear. Using rapid time-lapse two-photon calcium imaging of network activity and single-neuron growth within the unanesthetized developing brain, we demonstrate that visual stimulation induces coordinated changes to neuronal responses and dendritogenesis. Further, we identify the transcription factor MEF2A/2D as a major regulator of neuronal response to plasticity-inducing stimuli directing both structural and functional changes. Unpatterned sensory stimuli that change plasticity thresholds induce rapid degradation of MEF2A/2D through a classical apoptotic pathway requiring NMDA receptors and caspases-9 and -3/7. Knockdown of MEF2A/2D alone is sufficient to induce a metaplastic shift in threshold of both functional and morphological plasticity. These findings demonstrate how sensory experience acting through altered levels of the transcription factor MEF2 fine-tunes the plasticity thresholds of brain neurons during neural circuit formation.

Biomechanical adaptations enable phoretic mite species to occupy distinct spatial niches on host burying beetles.

Niche theory predicts that ecologically similar species coexist by minimizing interspecific competition through niche partitioning. Therefore, understanding the mechanisms of niche partitioning is essential for predicting interactions and coexistence between competing organisms. Here, we study two phoretic mite species, Poecilochirus carabi and Macrocheles nataliae that coexist on the same host burying beetle Nicrophorus vespilloides and use it to 'hitchhike' between reproductive sites. Field observations revealed clear spatial partitioning between species in distinct host body parts. Poecilochirus carabi preferred the ventral side of the thorax, whereas M. nataliae were exclusively found ventrally at the hairy base of the abdomen. Experimental manipulations of mite density showed that each species preferred these body parts, largely regardless of the density of the other mite species on the host beetle. Force measurements indicated that this spatial distribution is mediated by biomechanical adaptations, because each mite species required more force to be removed from their preferred location on the beetle. While P. carabi attached with large adhesive pads to the smooth thorax cuticle, M. nataliae gripped abdominal setae with their chelicerae. Our results show that specialist biomechanical adaptations for attachment can mediate spatial niche partitioning among species sharing the same host.

STAT5B mutations in myeloid neoplasms differ by disease subtypes but characterize a subset of chronic myeloid neoplasms with eosinophilia and/or basophilia.

STAT5B has been reported as a recurrent mutation in myeloid neoplasms (MNs) with eosinophilia, but the overall frequency and importance across a spectrum of MNs are largely unknown. We conducted a multicenter study on a series of 82 MNs with STAT5B mutations detected by next-generation sequencing. The estimated frequency of STAT5B mutation in MNs was low.

Acute presentations of eating disorders among adolescents and adults before and during the COVID-19 pandemic in Ontario, Canada.

BACKGROUND: Increased rates of pediatric eating disorders have been observed during the COVID-19 pandemic, but little is known about trends among adults. We aimed to evaluate rates of emergency department visits and hospital admissions for eating disorders among adolescents and adults during the pandemic. METHODS: We conducted a population-based, repeated cross-sectional study using linked health administrative data for Ontario residents aged 10-105 years during the prepandemic (Jan. 1, 2017, to Feb. 29, 2020) and pandemic (Mar. 1, 2020, to Aug. 31, 2022) periods. We evaluated monthly rates of emergency department visits and hospital admissions for eating disorders, stratified by age. RESULTS: Compared with expected rates derived from the prepandemic period, emergency department visits for eating disorders increased during the pandemic among adolescents aged 10-17 years (7.38 v. 3.33 per 100 000; incidence rate ratio [IRR] 2.21, 95% confidence interval [CI] 2.17-2.26), young adults aged 18-26 years (2.79 v. 2.46 per 100 000; IRR 1.13, 95% CI 1.10-1.16) and older adults aged 41-105 years (0.14 v. 0.11 per 100 000; IRR 1.15, 95% CI 1.07-1.24). Hospital admissions for eating disorders increased during the pandemic for adolescents (8.82 v. 5.74 per 100 000; IRR 1.54, 95% CI 1.54-1.54) but decreased for all adult age groups, especially older adults aged 41-105 years (0.21 v. 0.30 per 100 000; IRR 0.72, 95% CI 0.64-0.80). INTERPRETATION: Emergency department visits for eating disorders increased among adolescents, young adults and older adults during the pandemic, but hospital admissions increased only for adolescents and decreased for all adult groups. Differential rates of acute care use for eating disorders by age have important implications for allocation of inpatient mental health resources.

Risk of interpersonal violence during and after pregnancy among people with schizophrenia: a population-based cohort study.

BACKGROUND: Schizophrenia is associated with increased risk of experiencing interpersonal violence. Little is known about risk specifically around the time of pregnancy. METHODS: This population-based cohort study included all individuals (aged 15-49 yr) listed as female on their health cards who had a singleton birth in Ontario, Canada, between 2004 and 2018. We compared those with and without schizophrenia on their risk of an emergency department (ED) visit for interpersonal violence in pregnancy or within 1 year postpartum. We adjusted relative risks (RRs) for demographics, prepregnancy history of substance use disorder and history of interpersonal violence. In a subcohort analysis, we used linked clinical registry data to evaluate interpersonal violence screening and self-reported interpersonal violence during pregnancy. RESULTS: We included 1 802 645 pregnant people, 4470 of whom had a diagnosis of schizophrenia. Overall, 137 (3.1%) of those with schizophrenia had a perinatal ED visit for interpersonal violence, compared with 7598 (0.4%) of those without schizophrenia, for an RR of 6.88 (95% confidence interval [CI] 5.66-8.37) and an adjusted RR of 3.44 (95% CI 2.86-4.15). Results were similar when calculated separately for the pregnancy (adjusted RR 3.47, 95% CI 2.68-4.51) period and the first year postpartum (adjusted RR 3.45, 95% CI 2.75-4.33). Pregnant people with schizophrenia were equally likely to be screened for interpersonal violence (74.3% v. 73.8%; adjusted RR 0.99, 95% CI 0.95-1.04), but more likely to self-report it (10.2% v. 2.4%; adjusted RR 3.38, 95% CI 2.61-4.38), compared with those without schizophrenia. Among patients who did not self-report interpersonal violence, schizophrenia was associated with an increased risk for a perinatal ED visit for interpersonal violence (4.0% v. 0.4%; adjusted RR 6.28, 95% CI 3.94-10.00). INTERPRETATION: Pregnancy and postpartum are periods of higher risk for interpersonal violence among people with schizophrenia compared with those without schizophrenia. Pregnancy is a key period for implementing violence prevention strategies in this population.

The relationship between rurality, travel time to care and death by suicide.

BACKGROUND: We previously found an association between rurality and death by suicide, where those living in rural areas were more likely to die by suicide. One potential reason why this relationship exists might be travel time to care. This paper examines the relationship between travel time to both psychiatric and general hospitals and suicide, and then determine whether travel time to care mediates the relationship between rurality and suicide. METHODS: This is a population-based nested case-control study. Data from 2007 to 2017 were obtained from administrative databases held at ICES, which capture all hospital and emergency department visits across Ontario. Suicides were captured using vital statistics. Travel time to care was calculated from the resident's home to the nearest hospital based on the postal codes of both locations. Rurality was measured using Metropolitan Influence Zones. RESULTS: For every hour in travel time a male resides from a general hospital, their risk of death by suicide doubles (AOR = 2.08, 95% CI = 1.61-2.69). Longer travel times to psychiatric hospitals also increases risk of suicide among males (AOR = 1.03, 95%CI = 1.02-1.05). Travel time to general hospitals is a significant mediator of the relationship between rurality and suicide among males, accounting for 6.52% of the relationship between rurality and increased risk of suicide. However, we also found that there is effect modification, where the relationship between travel time and suicide is only significant among males living in urban areas. CONCLUSIONS: Overall, these findings suggest that males who must travel longer to hospitals are at a greater risk of suicide compared to those who travel a shorter time. Furthermore, travel time to care is a mediator of the association between rurality and suicide among males.

The impact of the COVID-19 pandemic on cardiovascular disease prevention and corresponding geographical inequalities in England: interrupted time series analysis.

BACKGROUND: There has been disruption to the detection and management of those with hypertension and atrial fibrillation (AF) during the COVID-19 pandemic. This is likely to vary geographically and could have implications for future mortality and morbidity. We aimed to estimate the change in diagnosed prevalence, treatment and prescription indicators for AF and hypertension and assess corresponding geographical inequalities. METHODS: Using the Quality and Outcomes Framework (2016/17 to 2021/22) and the English Prescribing Datasets (2018 to 2022), we described age standardised prevalence, treatment and prescription item rates for hypertension and AF by geography and over time. Using an interrupted time-series (ITS) analysis, we estimated the impact of the pandemic (from April 2020) on missed diagnoses and on the percentage change in medicines prescribed for these conditions. Finally, we described changes in treatment indicators against Public Health England 2029 cardiovascular risk targets. RESULTS: We observed 143,822 fewer (-143,822, 95%CI:-226,144, -61,500, p = 0.001) diagnoses of hypertension, 60,330 fewer (-60,330, 95%CI: -83,216, -37,444, p = 0.001) diagnoses of AF and 1.79% fewer (-1.79%, 95%CI: -2.37%, -1.22%), p < 0.0001) prescriptions for these conditions over the COVID-19 impact period. There was substantial variation across geography in England in terms of the indirect impact of the COVID-19 pandemic on the diagnosis, prescription, and treatment rates of hypertension and AF. 20% of Sub Integrated Care Boards account for approximately 62% of all missed diagnoses of hypertension. The percentage of individuals who had their hypertension controlled fell from 75.8% in 2019/20 to 64.1% in 2021/22 and the percentage of individuals with AF who were risk assessed fell from 97.2% to 90.7%. CONCLUSIONS: Hypertension and AF detection and management were disrupted during the COVID-19 pandemic. The disruption varied considerably across diseases and geography. This highlights the utility of administrative and geographically granular datasets to inform targeted efforts to mitigate the indirect impacts of the pandemic through applied secondary prevention measures.

Rurality as a Risk Factor for Attempted Suicide and Death by Suicide in Ontario, Canada.

OBJECTIVE: This study aims to examine rural and urban differences in attempted suicide and death by suicide in Ontario, Canada. METHOD: This is a population-based nested case-control study. Data were obtained from administrative databases held at ICES, which capture all hospital and emergency department visits across Ontario between 2007 and 2017. All adults living in Ontario who attempted suicide or died by suicide are included in the study, and controls were matched by sex and age. Suicides were captured using vital statistics. Suicide attempts were determined using emergency department service codes. RESULTS: Rurality is a risk factor for attempted suicide and death by suicide. Rural males are more likely to die by suicide compared with urban males (adjusted odds ratio(AOR) = 1.70, 95% confidence interval (CI), 1.49 to 1.95), and the odds of death by suicide increase with increasing levels of rurality. Rural males and females have an increased risk of attempted suicide compared with their urban counterparts (males: AOR = 1.37, 95% CI, 1.24 to 1.50) (females: AOR = 1.26, 95% CI, 1.14 to 1.39), with a pattern of increasing risk of suicide attempts with increasing rurality. Rural females are not at increased risk of suicide compared with urban females (AOR = 1.08, 95% CI, 0.80 to 1.45). Sensitivity analyses corroborated the results. CONCLUSIONS: Rural males are almost two times more likely to die by suicide compared with urban males, and both rural males and females have an elevated risk of suicide attempts compared with urban residents. Future research should examine potential mediators of the relationship between rurality and suicide.

Artificial intelligence for dermatopathology: Current trends and the road ahead.

Artificial intelligence (AI), including deep learning methods that leverage neural network-based algorithms, hold significant promise for dermatopathology and other areas of diagnostic pathology in research and clinical practice. There has been significant progress over past several years in applying AI to analyzing digital histopathology images for diagnosis. While much work in AI analysis of histopathology data remains investigational, recent regulatory agency approval in Europe and United States of AI-assisted tools for clinical use in histopathologic diagnosis of prostate and breast cancer herald broader movement of AI into the clinical diagnostic realm of anatomic pathology, including dermatopathology. However, significant challenges remain in translating AI from research into clinical practice, including algorithmic real-world performance, robustness to variation in data sets and practice settings, effective integration into clinical workflows, and cost effectiveness. This review introduces core concepts and terminology in AI, and assesses current progress and challenges in applying AI to dermatopathology.

Perinatal mental illness among women with disabilities: a population-based cohort study.

PURPOSE: To examine the risk of perinatal mental illness, including new-onset disorders and recurrent or ongoing use of mental health care, comparing women with physical, sensory, intellectual/developmental, and multiple disabilities to those without a disability. METHODS: From all women aged 15-49 years with a singleton birth in Ontario, Canada (2003-2018), those with physical (n = 144,972), sensory (n = 45,249), intellectual/developmental (n = 2,227), and ≥ 2 of these disabilities ("multiple disabilities"; n = 8,883), were compared to 1,601,363 without a disability on risk of healthcare system contact for mental illness from conception to 365 days postpartum. The cohort was stratified into: (1) no pre-pregnancy mental illness (to identify new-onset illness), (2) distal mental illness (> 2 years pre-pregnancy, to identify recurrent illness), and (3) recent mental illness (0-2 years pre-pregnancy, to identify ongoing contact). Modified Poisson regression generated relative risks (aRR), adjusted for age, parity, income quintile, and rural residence. RESULTS: About 14.7, 26.5, and 56.6% of women with no disabilities had new-onset, recurrent, and ongoing contact for mental illness, respectively, perinatally. Risks were elevated across disability groups for new-onset (physical: aRR 1.18, 95% CI 1.16-1.20; sensory: 1.11, 1.08-1.15; intellectual/developmental: 1.38, 1.17-1.62; multiple: 1.24, 1.15-1.33), recurrent (physical: 1.10, 1.08-1.12; sensory 1.06, 1.02-1.09; intellectual/developmental: 1.24, 1.11-1.37; multiple: 1.16, 1.09-1.23), and ongoing contact (physical: 1.09, 1.08-1.10; sensory: 1.08, 1.06-1.10; intellectual/developmental: 1.31, 1.26-1.37; multiple: 1.20, 1.16-1.23). CONCLUSION: The heightened use of new, recurrent, and ongoing mental health care across disability groups in the perinatal period suggests that adapted screening and intervention approaches are critical to optimize perinatal mental health in this population.