The Nexus of Climate Change, COVID-19, and Environmental Justice on Children\u27s Health

Climate change poses a threat to children, who are increasingly vulnerable, depending on adults to protect them from the impacts of these changes including extreme weather events, poor air and water quality and risk to mental health. Children living in poverty carry additional burdens and risks, living in environments that consistently experience poor air and water quality from polluting industries, compounded by the effects of climate change. COVID-19 has placed additional challenges to children’s health and increases the complexity of addressing climate change and environmental justice. The intersection between climate change and COVID-19 exacerbates these existing disparities by impacting children\u27s physical and mental health that are a direct product of poverty and structural racism. This article examines the nexus of climate change, COVID-19, and environmental justice that impacts the mental and physical health of children including anxiety, stress, adverse childhood experiences, and depression; increases in violence and aggression; and the effects of air pollution. Public health professionals and health care providers must be aware of national strategies that protect children from environmental health risks and emerging infectious diseases, such as climate change and COVID-19, respectively

Les perceptions des étudiants en médecine canadiens concernant la campagne Choisir avec soin

Background: Medical student investment in resource stewardship (RS) is essential as resource overuse continues among physicians, but it is unclear whether this is influenced by hidden curriculum. This study investigated medical student perceptions of Choosing Wisely Canada (CWC). Methods: Canadian Medical students completed a bilingual questionnaire. Chi-square and student’s T-tests were used to analyze Likert responses capturing student attitudes toward questions grouped by theme, including the importance of the CWC campaign, the amount of CWC represented in undergraduate medical curriculum, the application of CWC recommendations in medicine, and the barriers which exist to student advocacy for CWC in practice. Results: There were 3,239/11,754 (26.9%) respondents. While most students (n = 2,720/3,171; 85.8%) endorsed the importance of CWC, few students felt that their institution had sufficiently integrated CWC into pre-clerkship (47.0%) and clerkship (63.5%) curricula. Overall, 61.4% of students felt that it is reasonable to expect physicians to apply CWC recommendations given the workplace culture in medicine. Only 35.1% of students were comfortable addressing resource misuse with their preceptor. The most common barriers included the assumption that their preceptor was more knowledgeable (86.4%), concern over evaluations (66.0%), and concern for their reputation (31.2%).  Conclusions: Canadian medical students recognize the importance of CWC. However, many trainees feel that the workplace culture in medicine does not support the application of CWC recommendations. A power imbalance exists that prevents students from advocating for RS in practice.Contexte : Alors que les médecins continuent à surutiliser les ressources, l’investissement des étudiants en médecine dans l’intendance des ressources (IR) est essentiel, mais il n’est pas clair s’il s’agit d’un effet du curriculum caché. La présente étude examine les perceptions des étudiants en médecine concernant la campagne Choisir avec soin (CWC). Méthodes : Des étudiants en médecine canadiens ont été invités à remplir un questionnaire bilingue. Le test du chi carré et le test de Student ont été utilisés pour analyser leurs réponses, exprimées sur une échelle de Likert, reflétant leur position sur des questions regroupées par thème, notamment l’importance de la campagne CWC, le degré d’intégration des principes de la CWC dans le programme d’études médicales de premier cycle, l’application des recommandations de la CWC en médecine et les facteurs pratiques qui peuvent freiner la promotion de la CWC par les étudiants. Résultats : Parmi les 3 239/11 754 (26,9 %) répondants, la plupart (n=2 720/3 171 ; 85,8 %) reconnaissaient l’importance de la CWC, mais peu d’étudiants estiment que leur établissement ait suffisamment intégré la CWC au pré-externat (47,0 %) et à l’externat (63,5 %). Dans l’ensemble, 61,4 % des étudiants estiment qu’il est raisonnable d’attendre des médecins qu’ils appliquent les recommandations de la CWC compte tenu de la culture du lieu de travail en médecine. Seuls 35,1 % des étudiants sont à l’aise pour aborder la question de la mauvaise utilisation des ressources avec leur précepteur. Les obstacles les plus courants sont la supposition que leur précepteur est mieux informé qu’eux (86,4 %), la crainte des évaluations (66,0 %) et la crainte pour leur réputation (31,2 %). Conclusions : Les étudiants en médecine canadiens reconnaissent l’importance de la CWC. Cependant, de nombreux stagiaires estiment que la culture du lieu de travail en médecine ne favorise pas l’application des recommandations de la CWC. Le rapport de pouvoir qui y existe empêche les étudiants de défendre l’IR dans la pratique

SNX10 gene mutation leading to osteopetrosis with dysfunctional osteoclasts

Acknowledgements We sincerely thank the patients and family members who participated in this study. We would also like to thank Stefan Esher, Umeå University, for help with genealogy, and Anna Westerlund for excellent technical assistance. This work was supported by grants from the FOU, at the Umeå university hospital, and the Medical Faculty at Umeå University. The work at University of Gothenburg was supported by grants from The Swedish Research Council, the Swedish Rheumatism Association, the Royal 80-Year Fund of King Gustav V, ALF/LUA research grant from Sahlgrenska University Hospital in Gothenburg and the Lundberg Foundation. The work at the University of Gothenburg and the University of Aberdeen was supported by Euroclast, a Marie Curie FP7-People-2013-ITN: # 607446.Peer reviewedPublisher PD

LIM kinase inhibitors disrupt mitotic microtubule organization and impair tumor cell proliferation

The actin and microtubule cytoskeletons are critically important for cancer cell proliferation, and drugs that target microtubules are widely-used cancer therapies. However, their utility is compromised by toxicities due to dose and exposure. To overcome these issues, we characterized how inhibition of the actin and microtubule cytoskeleton regulatory LIM kinases could be used in drug combinations to increase efficacy. A previously-described LIMK inhibitor (LIMKi) induced dose-dependent microtubule alterations that resulted in significant mitotic defects, and increased the cytotoxic potency of microtubule polymerization inhibitors. By combining LIMKi with 366 compounds from the GSK Published Kinase Inhibitor Set, effective combinations were identified with kinase inhibitors including EGFR, p38 and Raf. These findings encouraged a drug discovery effort that led to development of CRT0105446 and CRT0105950, which potently block LIMK1 and LIMK2 activity in vitro, and inhibit cofilin phosphorylation and increase αTubulin acetylation in cells. CRT0105446 and CRT0105950 were screened against 656 cancer cell lines, and rhabdomyosarcoma, neuroblastoma and kidney cancer cells were identified as significantly sensitive to both LIMK inhibitors. These large-scale screens have identified effective LIMK inhibitor drug combinations and sensitive cancer types. In addition, the LIMK inhibitory compounds CRT0105446 and CRT0105950 will enable further development of LIMK-targeted cancer therapy

Exfoliated Nanocomposites Based on Polyaniline and Tungsten Disulfide

Nanocomposite materials consisting of polyaniline (PANI) and exfoliated WS2 were synthesized. The WS2 was prepared by reacting tungstic acid with thiourea at 500°C under nitrogen flow. Samples were prepared with a WS2 content of 1, 5, 7.5, 10, 12.5, 15, 20, 37, and 64% by mass. An improvement in the electronic conductivity value of the PANI was observed through the incorporation of exfoliated WS2. The electronic conductivity of PANI-15%WS2 was 24.5 S/cm, an eightfold increase when compared to pure PANI. Powder X-ray diffraction (XRD), transmission electron microscopy (TEM) and electron paramagnetic resonance (EPR) provided evidence that the nanocomposites are in an exfoliated state. XRD and TEM showed that the nanocomposites were completely amorphous, suggesting lack of structural order in these materials, while their EPR signals were considerably narrower compared to pure PANI, indicating the formation of genuine exfoliated systems. Furthermore, our research showed that WS2 can be used as a filler to improve activation energy of decomposition of the polymer. By using the Ozawa method, we studied the decomposition kinetics for the nanocomposites, as well as for the pure polymer. The activation energy for the decomposition of pure PANI was found to be 131.2 kJ/mol. Increasing the amount of WS2 to 12.5% in the PANI increases the activation energy of decomposition to 165.4 kJ/mol, an enhancement of 34.2 kJ/mol over the pure polymer

The Circadian Clock Protein BMAL1 Acts as a Metabolic Sensor In Macrophages to Control the Production of Pro IL-1β

The transcription factor BMAL1 is a clock protein that generates daily or circadian rhythms in physiological functions including the inflammatory response of macrophages. Intracellular metabolic pathways direct the macrophage inflammatory response, however whether the clock is impacting intracellular metabolism to direct this response is unclear. Specific metabolic reprogramming of macrophages controls the production of the potent pro-inflammatory cytokine IL-1β. We now describe that the macrophage molecular clock, through Bmal1, regulates the uptake of glucose, its flux through glycolysis and the Krebs cycle, including the production of the metabolite succinate to drive Il-1β production. We further demonstrate that BMAL1 modulates the level and localisation of the glycolytic enzyme PKM2, which in turn activates STAT3 to further drive Il-1β mRNA expression. Overall, this work demonstrates that BMAL1 is a key metabolic sensor in macrophages, and its deficiency leads to a metabolic shift of enhanced glycolysis and mitochondrial respiration, leading to a heightened pro-inflammatory state. These data provide insight into the control of macrophage driven inflammation by the molecular clock, and the potential for time-based therapeutics against a range of chronic inflammatory diseases

Occupational safety and health considerations of returning to work after cancer

Increasing numbers of people undergo a return to work (RTW) after a cancer diagnosis and treatment. Although there is evidence available in relation to managing the RTW process, at the current time, there is limited information available in relation to any safety and health issues associated with this process. Using a systematic review and organisational case studies, this project aimed to understand the health and safety implications of returning to work or staying in work during treatment, to identify what employers can do to facilitate this process for cancer survivors and to develop guidance for IOSH from the work carried out. The systematic review identified that understanding the potential changes in individual capacity (both physical and mental) are essential, as are the role of the line manager, being able to offer flexibility in returning to work, and understanding that the process can be long term. The case studies aimed to identify good practice and found that different aspects can impact on the RTW or continuation to work, including using risk assessments of work tasks rather than job roles, and considering the impact of physical and psychological demands. Different factors need to be considered within the risk assessment, including the impact of fatigue, risks of infection, work planning and breaks in the working day, the inclusion of emergency planning, and flexibility in start times or workplace. The work has also highlighted a number of evidence gaps, including: the lack of an evidence base for safety, health or ergonomic interventions; a lack of information in relation to manual workers and their RTW needs; a lack of information on those who have had to change jobs or on their future employability; and a need for more in-depth, longer-term research. Content for an IOSH OH Toolkit on RTW after cancer was also produced as part of this work

Mechanisms of change in the evolution of jargon aphasia

Background: The evolution of jargon aphasia may reflect recovery in the speech production processes. Alternatively or additionally there may be improved self-monitoring, enabling the person to suppress jargon errors. Previous case reports offer evidence for both mechanisms of change, and suggest that they can co-occur. Aims: This longitudinal study aimed to uncover mechanisms of change in an individual with jargon aphasia. Four predictions of production processing recovery were examined against test data. The study also looked for evidence of improved error awareness, in both test and connected speech data, and explored the relationship between this improvement and the production gains. Methods & Procedures: The participant (TK) undertook tests of single word naming, reading and repetition eight times over a 21-month period, with matched sets of nouns and verbs. Analyses of correct responses and errors were conducted, in order to test predictions of processing recovery. Changes in self-monitoring behaviours were also investigated, to uncover evidence of increased error awareness. Finally, longitudinal changes in samples of connected speech were explored. Outcomes & Results: Two predictions of production processing recovery were upheld: there was a significant increase in the number of correct responses over time, and a significant decrease in the proportion of nonword errors. The error analysis also revealed a trend towards increased target-relatedness and decreased perseveration, but neither was significant. There was an increase in self-monitoring behaviours during testing, in that there were more null responses and attempted self-corrections. This increase correlated very strongly with the production gains. Connected speech showed little evidence of improved production, since the range of vocabulary employed by TK reduced as time progressed. However, self-monitoring behaviours were increasingly evident in this context. Conclusions: The origin of the production and monitoring gains experienced by TK are discussed. Implications are drawn out for further research

Investigating the Potential and Pitfalls of EV-Encapsulated MicroRNAs as Circulating Biomarkers of Breast Cancer

Extracellular vesicles (EVs) shuttle microRNA (miRNA) throughout the circulation and are believed to represent a fingerprint of the releasing cell. We isolated and characterized serum EVs of breast tumour-bearing animals, breast cancer (BC) patients, and healthy controls. EVs were characterized using transmission electron microscopy (TEM), protein quantification, western blotting, and nanoparticle tracking analysis (NTA). Absolute quantitative (AQ)-PCR was employed to analyse EV-miR-451a expression. Isolated EVs had the appropriate morphology and size. Patient sera contained significantly more EVs than did healthy controls. In tumour-bearing animals, a correlation between serum EV number and tumour burden was observed. There was no significant relationship between EV protein yield and EV quantity determined by NTA, highlighting the requirement for direct quantification. Using AQ-PCR to relate miRNA copy number to EV yield, a significant increase in miRNA-451a copies/EV was detected in BC patient sera, suggesting potential as a novel biomarker of breast cancer