Purpose of review: This paper reports a review of the empirical research examining the association between mass trauma media contact and depression in children, the factors that may influence the association, and the difficulties encountered in the study of media effects on depression.

Recent findings: All of the included studies assessed general population samples. Pre-COVID-19 research focused primarily on television coverage alone or on multiple media forms including television, while COVID-19 media studies examined various media forms including social media. Most studies used cross-sectional design and non-probability sampling. The review revealed inconclusive findings across studies. The study of mass trauma media effects on depression in children is complicated by a number of potential confounding factors and by the relatively high prevalence of depression in the general population. Media contact was a relatively minor consideration among other interests in the extant studies which failed to explore numerous issues that warrant attention in future research.

Keywords: Children and COVID-19; Children and disasters; Children and terrorism; Depression; Disaster media coverage; Mass trauma media coverage.

Cholesterol serves as an essential lipid molecule in various membrane organelles of mammalian cells. The metabolites of cholesterol also play important functions. Acyl-coenzyme A: cholesterol acyltransferase 1 (ACAT1), also named as sterol O-acyltransferase 1, is a membrane-bound enzyme residing at the endoplasmic reticulum (ER). It converts cholesterol to cholesteryl esters (CEs) for storage, and is expressed in all cells. CEs cannot partition in membranes; they can only coalesce as cytosolic lipid droplets. Excess CEs are found in the vulnerable region of the brains of patients with late-onset Alzheimer's disease (AD), and in cell and mouse models for AD. Reducing CE contents by genetic inactivation of ACAT1, or by pharmacological inhibition of ACAT is shown to reduce amyloidopathy and other hallmarks for AD. To account for the various beneficial actions of the ACAT1 blockade (A1B), a working hypothesis is proposed here: the increase in CE contents observed in the AD brain is caused by damages of cholesterol-rich lipid rafts that are known to occur in neurons affected by AD. These damages cause cholesterol to release from lipid rafts and move to the ER where it will be converted to CEs by ACAT1. In addition, the increase in CE contents may also be caused by overloading with cholesterol-rich substances, or through activation of ACAT1 gene expression by various proinflammatory agents. Both scenarios may occur in microglia of the chronically inflamed brain. A1B ameliorates AD by diverting the cholesterol pool destined for CE biosynthesis such that it can be utilized more efficiently to repair membrane damage in various organelles, and to exert regulatory actions more effectively to defend against AD. To test the validity of the A1B hypothesis in cell culture and in vivo, the current status of various anti-ACAT1 agents that could be further developed is briefly discussed.

Keywords: Alzheimer’s disease; cholesterol; cholesterol acyltransferase.

Bisphenol A (BPA) is one of the most widely studied endocrine disrupting chemicals because of its structural similarity to 17-β estradiol; its ability to bind as an agonist/antagonist to estrogen receptors elicits adverse effects on the functioning of the metabolic and endocrinal system. Therefore, BPA has been thoroughly scrutinized concerning its disruption of pathways like lipid metabolism, steroidogenesis, insulin signaling, and inflammation. This has resulted in reports of its correlation with various aspects of cardiovascular diseases, obesity, diabetes, male and female reproductive disorders, and dysfunctions. Among these, the occurrence of the polycystic ovarian syndrome (PCOS) in premenopausal women is of great concern. PCOS is a highly prevalent disorder affecting women in their reproductive age and is clinically characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology, along with metabolism-related dysfunctions like hyperinsulinemia, obesity, and insulin resistance. In this review, we analyzed certain researched effects of BPA, while focusing on its ability to alter the expression of various significant genes like GnRH, AdipoQ, ESR1, StAR, CYP11A1, CYP19A1, and many more involved in the pathways and endocrine regulation, whose disruption is commonly associated with the clinical manifestations of PCOS.

Keywords: Bisphenol A; Gene expression; Gonadotropins; Hormones; Polycystic ovarian syndrome; Steroidogenesis.

Mitochondria are energy-producing organelles, and neurons are high energy consumption cells. Therefore, mitochondrial dysfunction is a critical factor in neurodegenerative processes. Mitochondrial division inhibitor-1 (Mdivi-1) is a small chemical inhibitor of mitochondrial division dynamin, which plays multiple roles in mitochondrial dynamics, mitochondrial autophagy, ATP production, the immune response, and Ca2+ homeostasis. Mdivi-1 inhibition of excessive mitochondrial fission exerted cytoprotective effects in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Mdivi-1 changed the mRNA expression of the electron transport chain (ETC) and reduced Ca2+ overload against neuronal injury. Elucidation of the molecular mechanism of Mdivi-1 in neurodegenerative diseases will help evaluate its therapeutic potential and promote its application in clinical studies. The present article focused on the multiple effects of Mdivi-1 on mitochondrial function and its potential therapeutic effects in neurodegenerative diseases.

Background: As the number of late-career pediatric hospitalists increases, issues regarding aging and retirement will require more attention. Long shifts and overnight clinical responsibilities may be challenging for older physicians. Our study objectives include investigation of the current state of practice regarding work hours, night call responsibilities, productivity requirements, coronavirus disease 2019 (COVID-19) exposure modifications, and division chief knowledge about retirement supports for late-career pediatric hospitalists.

Methods: This cross-sectional study used a web survey, distributed in spring of 2020 on the American Academy of Pediatrics, Section on Hospital Medicine, Division Chief listserv. The questionnaire asked about (1) program demographics, (2) overnight call responsibilities, (3) clinical schedules, (4) modifications for COVID-19, and (5) retirement benefits and supports. Data were analyzed by using descriptive statistics and the Fisher exact test.

Results: The 47 responding programs employ 982 hospitalists in 728 full-time equivalent positions. Division chiefs estimated 117 (12%) individuals were aged 50 to 64 years and 16 (1.6%) were 65 years or older. Most programs (91%) had at least 1 member 50 to 64 years of age; 13 programs (28%) had a member aged 65 or older. Larger programs were more likely to allow older physicians to opt out of some night call responsibilities. Most programs made some accommodations for COVID-19 exposure. Other than financial counseling and academic benefits, most programs did not provide retirement counseling or other supports for retiring physicians.

Conclusion: Although limited by a low response rate, we found most programs had older faculty. Substantial variation exists in how programs make accommodations and offer support for older members.

We had the fortune of starting our scientific /research careers in the Molecular Biology and Crop Biotechnology laboratory of Professor P.K. Gupta at Ch. Charan Singh University, Meerut, U.P., India. Here, we describe most important scientific contributions of our beloved mentor in the area of cytotaxonomy, cytogenetics, mutation breeding, quantitative genetics, molecular biology, crop biotechnology and plant genomics, on his 85^th birthday. Important contributions made in development and use of genomics resources including development and use of different kinds of molecular markers, genetic and physical mapping, QTL interval mapping, genome-wide association mapping, molecular breeding including marker-assisted selection (MAS) have been briefly summarized. Efforts have been also made to give readers a glimpse of important contributions in the study of cytology/apomixis of grasses, cytotaxonomic studies in asteraceae/fabaceae, nuclear /repetitive DNA content in Lolium, Interspecific/intergeneric relationships involving the genus Hordeum and re-examining taxonomy of the tribe Triticeae.

Keywords: Cytogenetics; Cytotaxonomy; GWAS; Gene pyramiding; Genetic maps; Genetic resources; Marker-assisted selection; Markers; Mutation breeding; QTLs; SNPs; SSRs.

Histone acetylation is one of the epigenetic modifications. Histone acetylation, which is catalyzed by histone acetyltransferases and negatively regulated by histone deacetylases, plays an important role in a variety of cellular physiological and pathophysiological processes. Recent studies have shown that histone deacetylases are involved in a variety of pathophysiological responses to acute kidney injury, such as apoptosis, dedifferentiation, proliferation and regeneration. This article reviews the role and underlying mechanism of histone deacetylases in acute kidney injury induced by ischemia reperfusion, nephrotoxicants, sepsis and rhabdomyolysis.

Bisphosphonates are widely used as anti-resorptive agents for the treatment of various bone and joint diseases, including advanced osteoporosis, multiple myeloma, bone metastatic cancers, Paget's disease of bone, and rheumatoid arthritis. Bisphosphonates act as an anti-osteoclast via the induction of osteoclast apoptosis, resulting in a decreased rate of bone resorption. Unfortunately, there is much evidence to demonstrate that the long-term use of bisphosphonates is associated with osteonecrosis. The pathogenesis of osteonecrosis includes the death of osteoblasts, osteoclasts, and osteocytes. In addition, the functions of endothelial cells, epithelial cells, and fibroblasts are impaired in osteonecrosis, leading to disruptive angiogenesis, and delayed wound healing. Osteonecrosis is most commonly found in the jawbone and the term medication-related osteonecrosis of the jaw (MRONJ) has become the condition of greatest clinical concern among patients receiving bisphosphonates. Although surgical treatment is an effective strategy for the treatment of MRONJ, several non-surgical interventions for the attenuation of MRONJ have also been investigated. With the aim of increasing understanding around MRONJ, we set out to summarize and discuss the holistic effects of bisphosphonates on the bone and its surrounding tissues. In addition, non-surgical interventions for the attenuation of bisphosphonate-induced osteonecrosis were reviewed and discussed.

Keywords: Bisphosphonates; Drug toxicity; Medication-related osteonecrosis of the jaw; Osteonecrosis.

SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has evolved many variants with stronger infectivity and immune evasion than the original strain, including Alpha, Beta, Gamma, Delta, Epsilon, Kappa, Iota, Lambda, and 21H strains. Amino acid mutations are enriched in the spike protein of SARS-CoV-2, which plays a crucial role in cell infection. However, the impact of these mutations on protein structure and function is unclear. Understanding the pathophysiology and pandemic features of these SARS-CoV-2 variants requires knowledge of the spike protein structures. Here, we obtained the spike protein structures of 10 main globally endemic SARS-CoV-2 strains using AlphaFold2. The clustering analysis based on structural similarity revealed the unique features of the mainly pandemic SARS-CoV-2 Delta variants, indicating that structural clusters can reflect the current characteristics of the epidemic more accurately than those based on the protein sequence. The analysis of the binding affinities of ACE2-RBD, antibody-NTD, and antibody-RBD complexes in the different variants revealed that the recognition of antibodies against S1 NTD and RBD was decreased in the variants, especially the Delta variant compared with the original strain, which may induce the immune evasion of SARS-CoV-2 variants. Furthermore, by virtual screening the ZINC database against a high-accuracy predicted structure of Delta spike protein and experimental validation, we identified multiple compounds that target S1 NTD and RBD, which might contribute towards the development of clinical anti-SARS-CoV-2 medicines. Our findings provided a basic foundation for future in vitro and in vivo investigations that might speed up the development of potential therapies for the SARS-CoV-2 variants.

Introduction: People with end-of-life care needs are seen in an increasingly diverse range of health and community settings. Opportunity for continued occupational participation is highly valued by people at the end of life. This scoping review sought to identify the priorities and preferences for participation at the end of life and to map findings using the model of human occupation.

Methods: A search strategy informed by the research question was developed in collaboration with a research librarian. Data sources used were Ovid Medline(R), CINAHL, Ovid Emcare, Scopus, Web of Science and PsychInfo. Studies that focused on clinician perspectives, clinical care, grief and loss, did not clearly identify end-stage diseases, <18 years and written in languages other than English were excluded.

Findings: Forty-four studies were included with a total of 1,070 study participants. Inductively developed themes were mapped against the model of human occupation constructs of volition (personal causation, values, interests), habituation (habits of occupational performance and routine), performance capacity and the lived body within the physical, social and occupational environment. The majority of findings sat within the construct of volition, particularly around sense of personal capacity, self-efficacy and values. At the end of life, people prioritise ongoing engagement in valued occupations even if participation is effortful. As disease progresses, opportunity to exert influence and control over this participation and engagement increases in importance. Personal causation plays an important role in the experience of occupational participation at this time.

Conclusion: This review provides important insights into the occupational priorities of people at the end of life and the importance of supporting agency and volition at this time. The model of human occupation and its client-centred focus offer a framework for a more robust examination of ways to enhance volitional capacity and enable occupational participation for people at the end of life.

Keywords: end-of-life care; model of human occupation; occupational therapy; palliative care; volition.

Carbon hydrogasification is the slowest reaction among all carbon-involved small molecule transformations. Here, we demonstrate a mechanochemical method that results in both a faster reaction rate and a new synthesis route. The reaction rate was dramatically enhanced by up to 4 orders of magnitude compared to the traditional thermal method. Simultaneously, the reaction exhibited very high selectivity (99.8% CH4, versus 80% under thermal conditions) with a cobalt catalyst. Our study demonstrated that this extreme increase in reaction rate originates from the continuous activation of reactive carbon species via mechanochemistry. The high selectivity is intimately related to the activation at low temperature, at which higher hydrocarbons are difficult to form. This work is expected to advance studies of carbon hydrogasification, and other solid-gas reactions.

Keywords: Mechanochemistry; carbon-neutral; hydrogenation; methane; solid-gas reaction.

Understanding the state of sleep health in First Nations Australians offers timely insight into intervention and management opportunities to improve overall health and well-being. This review explored the determinants and burden of poor sleep in First Nations Australians. A systematic search was conducted to identify studies published until August 2020 in First Nations Australian adults. Nine studies (n = 2640) were included, three in community settings, six in clinical populations. Across studies compared with non-Indigenous people, 15-34% of First Nations Australians experience less than recommended hours (<7 h/night), 22% reported fragmented, irregular, and unrefreshing sleep with a high prevalence of OSA in clinical populations (39-46%). Findings show First Nations Australians are significantly more likely to report worse sleep health than Non-Indigenous Australians in all measured domains of sleep. Co-designed sleep programs and service delivery solutions are necessary to ensure timely prevention and management of sleep issues in First Nations communities which to date have been underserved.

Funding: No external funding was provided for this work.

In this perspective, we develop a matrix for auditing algorithmic decision-making systems (ADSs) used in the hiring domain. The tool is a socio-technical assessment of hiring ADSs that is aimed at surfacing the underlying assumptions that justify the use of an algorithmic tool and the forms of knowledge or insight they purport to produce. These underlying assumptions, it is argued, are crucial for assessing not only whether an ADS works "as intended," but also whether the intentions with which the tool was designed are well founded. Throughout, we contextualize the use of the matrix within current and proposed regulatory regimes and within emerging hiring practices that incorporate algorithmic technologies. We suggest using the matrix to expose underlying assumptions rooted in pseudo-scientific essentialized understandings of human nature and capability and to critically investigate emerging auditing standards and practices that fail to address these assumptions.

Keywords: accountability; audit; automated decision-making systems; hiring.

The delivery of small molecule fluorophores with minimal compartmentalization is currently one of the most critical technical problems in intracellular labelling. Here we introduce sulfonated and phosphonated coumarin dyes, demonstrate rapid cell entry via a prodrug approach, and show a lack of interaction with membranes, organelles, or other compartments. The dyes show no specific localization and are evenly distributed in the cells. Our fluorogenic, clickable phosphonate derivatives successfully tagged model targets in intact cells and the increase in brightness upon click reaction was around 60-fold.

Keywords: cellular location; click chemistry; fluorogenic dyes; live-cell imaging; membrane permeable dyes.

Background: The T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign, has been considered a highly specific imaging biomarker of IDH-mutant, 1p/19q noncodeleted low-grade glioma. This systematic review and meta-analysis aimed to evaluate the diagnostic performance of T2-FLAIR mismatch sign for prediction of a patient with IDH-mutant, 1p/19q noncodeleted low-grade glioma, and identify the causes responsible for the heterogeneity across the included studies.

Methods: A systematic literature search in the Ovid-MEDLINE and EMBASE databases was performed for studies reporting the relevant topic before November 17, 2020. The pooled sensitivity and specificity values with their 95% confidence intervals were calculated using bivariate random-effects modeling. Meta-regression analyses were also performed to determine factors influencing heterogeneity.

Results: For all the 10 included cohorts from 8 studies, the pooled sensitivity was 40% (95% confidence interval [CI] 28-53%), and the pooled specificity was 100% (95% CI 95-100%). In the hierarchic summary receiver operating characteristic curve, the difference between the 95% confidence and prediction regions was relatively large, indicating heterogeneity among the studies. Higgins I² statistics demonstrated considerable heterogeneity in sensitivity (I² = 83.5%) and considerable heterogeneity in specificity (I² = 95.83%). Among the potential covariates, it seemed that none of factors was significantly associated with study heterogeneity in the joint model. However, the specificity was increased in studies with all the factors based on the differences in the composition of the detailed tumors.

Conclusions: The T2-FLAIR mismatch sign is near-perfect specific marker of IDH mutation and 1p/19q noncodeletion.

Keywords: astrocytic; biomarker; glioma; molecular genetics.

Aims: The new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimating glomerular filtration rate (eGFR), based on serum creatinine, that does not incorporate race may reclassify individuals, irrespective of race, from one eGFR category to another, with implications for eligibility for treatments in patients with heart failure and reduced ejection fraction (HFrEF).

Methods and results: A total of 43,138 ambulatory patients with HFrEF from 12 clinical trials were included (mean age 64.3 years; 9,580 (22.2%) women). Mean eGFR was 67 (SD 21) ml/min/1.73m² and 70 (SD 21) ml/min/1.73m² using the original and new CKD-EPI equations, respectively (mean difference 3.20 [95%CI, 3.17-3.23] ml/min/1.73m² , P<0.001). Of the 935 patients with CKD stages 4 or 5, identified using the original equation, 309 (33.0%) were reclassified to CKD stages 1-3 (eGFR ≥30ml/min/1.73m² ) with the new equation. However, the opposite was observed among the 2,521 Black patients (5.8%) included, with a reduction in mean eGFR from 75 to 68ml/min/1.73m² using the original and new equations, respectively (mean difference 6.94 [95%CI, 6.82-7.06] ml/min/1.73m² , P<0.001). The number of Black patients with an eGFR<30ml/min/1.73m² increased from 49 (1.9%) using the original equation to 71 (2.8%) with the new equation.

Conclusions: The new CKD-EPI creatinine equation reclassified CKD stage in a large percentage of patients with HFrEF enrolled in clinical trials. As eGFR is a key determinant of eligibility for several key pharmacological therapies in HFrEF, this reclassification could result in a substantial change in the proportion of patients considered eligible for such therapies and reduce the proportion of Black patients eligible.

Introduction: Gender bias has been identified consistently in written performance evaluations. Qualitative tools may provide a standardized way to evaluate surgical skill and minimize gender bias. We hypothesized that there is no difference in operative time or GEARS scores in robotic hysterectomy for men vs women surgeons.

Methods: Patients undergoing robotic hysterectomies performed between June 2019 and March 2020 at 8 hospitals within the same hospital system were captured into a prospective database. GEARS scores were assigned by crowd-sourced evaluators by a third party blinded to any surgeon- or patient-identifying information. One-way ANOVA was used to compare the mean operative time and GEARS scores for each group, and significant variables were included in a one-way ANCOVA to control for confounders. Two-tailed p-value < 0.05 was considered significant.

Results: Seventeen women and 13 men performed a total of 188 hysterectomies; women performed 34 (18%) and men performed 153 (81%). Women surgeons had a higher mean operative time (133 ± 58 vs 86.3 ± 46 min, p = 0.024); after adjustment, there were no significant differences in operative time (p = 0.607). There was no significant difference between the genders in total GEARS score (20.0 ± 0.77 vs 20.2 ± 0.70, p = 0.415) or GEARS subcomponent scores: bimanual dexterity (3.98 ± 0.03 vs 4.00 ± 0.03, p = 0.705); depth perception (4.04 ± 0.04 vs 4.05 ± 0.02, p = 0.799); efficiency (3.79 ± 0.02 vs 3.82 ± 0.02, p = 0.437); force sensitivity (4.01 ± 0.04 vs 4.05 ± 0.05, p = 0.533); or robotic control (4.16 ± 0.03 vs 4.26 ± 0.01, p = 0.079).

Conclusion: There was no difference in GEARS score between men vs women surgeons performing robotic hysterectomies. Video-based blinded assessment of skills may minimize gender biases when evaluating surgical skill for competency evaluation and credentialing.

Keywords: Disparities; Education; Gender; Video-based assessment.

Background: Positive behavioural support (PBS) can be effective in supporting children and young people (CYP) with developmental disabilities. This systematic review focused on describing the components and nine characteristics of PBS that have been used with CYP with developmental disabilities in special education settings, and the evidence for PBS effectiveness in these settings. Additionally, facilitators and barriers to PBS implementation, and experiences of stakeholders, were investigated.

Method: Systematic searches followed a registered protocol, and 30 studies were identified, narratively synthesised, and critically appraised.

Results: From the 30 studies included, 10 reported the presence of all 9 PBS characteristics, 17 reported on 8 PBS characteristics, and 3 reported on 7 characteristics. Overall, 28 studies demonstrated significant decreases in behaviours that challenge and increases in alternative behaviours, if increasing alternative behaviours was part of the interventions.

Conclusions: There was a lack of evidence on facilitators and barriers, and a lack of qualitative studies exploring experiences of stakeholders with PBS in special education settings. The available evidence suggested that not all studies reported on all PBS characteristics when describing the approach followed. In addition, available evidence suggested that most studies demonstrated effectiveness of PBS regarding the measured outcomes. Implications and future directions are discussed.

Keywords: autism; functional behaviour assessment; intellectual disability; positive behavioural support(s); special education; systematic review.

Radiation therapy for patients with pN1mi or pN1 disease breast cancer undergoing mastectomy has been debated for a long time. Even in low metastatic burden in sentinel node biopsy, occult non-sentinel axillary nodal involvement can exist. Radiotherapy can sterilize axillary metastatic burden and seems to contribute a very low local recurrence rate in mastectomy patients with minimally involved lymph nodes. However, it should be considered that systemic therapy is evolving and the local recurrence difference between radiotherapy and no radiotherapy is relatively small. Regarding postmastectomy radiotherapy in patients pN1mi or pN1 cancer, published prospective clinical trial results should be considered; however, there are no such relevant results of clinical trials yet. Consideration of postmastectomy radiation therapy in pN1mi or pN1 patients should be based on identifying the high-risk group in terms of recurrence, stage, or tumor biology. When radiotherapy is determined, radiation oncologists should attempt individualized treatment approaches, such as irradiation field, and consider specific settings, such as neoadjuvant therapy. In this review, the role of radiotherapy in mastectomy patients with minimally involved lymph nodes and the relevant considerations are discussed.

Keywords: Breast Neoplasms; Lymph Nodes; Mastectomy; Radiotherapy.

Medicine is undergoing an unprecedented digital transformation, as massive amounts of health data are being produced, gathered, and curated, ranging from in-hospital (e.g., intensive care unit [ICU]) to person-generated data (wearables). Annotating all these data for training purposes in order to feed to deep learning models for pattern recognition is impractical. Here, we discuss some exciting recent results of self-supervised learning (SSL) applications to high-resolution health signals. These examples leverage unlabeled data to learn meaningful representations that can generalize to situations where the ground truth is inadequate or simply infeasible to collect due to the high burden or associated costs. The most prominent bottleneck of deep learning today is access to labeled, carefully curated datasets, and self-supervision on health signals opens up new possibilities to eliminate data silos through general-purpose models that can transfer to low-resource environments and tasks.

Keywords: biomedical informatics; health signals; machine learning; transfer learning.