Highlights Healthcare workers’ mental health problems correlate with organizational factors such as workload and exposure to covid-19 patients. Healthcare workers are more interested in occupational protection, rest, and social support than in professional psychological help. Interventions focus more on addressing individual psychopathology, which points towards a mismatch between what workers want and need, and the services available to them.

Introduction The novel Coronavirus Disease (COVID-19) outbreak currently puts health care workers at high risk of both physical and mental health problems. This study aimed to identify the risk and protective factors for mental health outcomes in health care workers during coronavirus epidemics. Methods A rapid systematic review was performed in three databases (March 24, 2020) and a current COVID-19 resource (May 28, 2020). Following study selection, study characteristics and effect measures were tabulated, and data were synthesized by using vote counting. Meta-analysis was not possible because of high variation in risk factors, outcomes and effect measures. Risk of bias of each study was assessed and the certainty of evidence was appraised according to the GRADE methodology. Results Out of 2605 references, 33 observational studies were selected and the identified risk and protective factors were categorized in ten thematic categories. Most of these studies (n = 23) were performed during the SARS outbreak, seven during the current COVID-19 pandemic and three during the MERS outbreak. The level of disease exposure and health fear were significantly associated with worse mental health outcomes. There was evidence that clear communication and support from the organization, social support and personal sense of control are protective factors. The evidence was of very low certainty, because of risk of bias and imprecision. Conclusion Safeguarding mental health of health care workers during infectious disease outbreaks should not be treated as a separate mental health intervention strategy, but could benefit from a protective approach. This study suggests that embedding mental health support in a safe and efficient working environment which promotes collegial social support and personal sense of control could help to maximize resilience of health care workers. Low quality cross-sectional studies currently provide the best possible evidence, and further research is warranted to confirm causality.

The metalloproteinase ADAM10 is of importance for Notch-dependent cortical brain development. The protease is tightly linked with ␣-secretase activity toward the amyloid precursor protein (APP) substrate. Increasing ADAM10 activity is suggested as a therapy to prevent the production of the neurotoxic amyloid ␤ (A␤) peptide in AlzheimerЈs disease. To investigate the function of ADAM10 in postnatal brain, we generated Adam10 conditional knock-out (A10cKO) mice using a CaMKII␣-Cre deleter strain. The lack of ADAM10 protein expression was evident in the brain cortex leading to a reduced generation of sAPP␣ and increased levels of sAPP␤ and endogenous A␤ peptides. The A10cKO mice are characterized by weight loss and increased mortality after weaning associated with seizures. Behavioral comparison of adult mice revealed that the loss of ADAM10 in the A10cKO mice resulted in decreased neuromotor abilities and reduced learning performance, which were associated with altered in vivo network activities in the hippocampal CA1 region and impaired synaptic function. Histological and ultrastructural analysis of ADAM10-depleted brain revealed astrogliosis, microglia activation, and impaired number and altered morphology of postsynaptic spine structures. A defect in spine morphology was further supported by a reduction of the expression of NMDA receptors subunit 2A and 2B. The reduced shedding of essential postsynaptic cell adhesion proteins such as N-Cadherin, Nectin-1, and APP may explain the postsynaptic defects and the impaired learning, altered network activity, and synaptic plasticity of the A10cKO mice. Our study reveals that ADAM10 is instrumental for synaptic and neuronal network function in the adult murine brain.

BackgroundAlpha-synuclein is a key protein implicated in the pathogenesis of Parkinson's disease (PD). It is the main component of the Lewy bodies, a cardinal neuropathological feature in the disease. In addition, whole locus multiplications and point mutations in the gene coding for alpha-synuclein lead to autosomal dominant monogenic PD. Over the past decade, research on PD has impelled the development of new animal models based on alpha-synuclein. In this context, transgenic mouse lines have failed to reproduce several hallmarks of PD, especially the strong and progressive dopaminergic neurodegeneration over time that occurs in the patients. In contrast, viral vector-based models in rats and non-human primates display prominent, although highly variable, nigral dopaminergic neuron loss. However, the few studies available on viral vector-mediated overexpression of alpha-synuclein in mice report a weak neurodegenerative process and no clear Lewy body-like pathology. To address this issue, we performed a comprehensive comparative study of alpha-synuclein overexpression by means of recombinant adeno-associated viral vectors serotype 2/7 (rAAV2/7) at different doses in adult mouse substantia nigra.ResultsWe noted a significant and dose-dependent alpha-synucleinopathy over time upon nigral viral vector-mediated alpha-synuclein overexpression. We obtained a strong, progressive and dose-dependent loss of dopaminergic neurons in the substantia nigra, reaching a maximum of 82% after 8 weeks. This effect correlated with a reduction in tyrosine hydroxylase immunoreactivity in the striatum. Moreover, behavioural analysis revealed significant motor impairments from 12 weeks after injection on. In addition, we detected the presence of alpha-synuclein-positive aggregates in the remaining surviving neurons. When comparing wild-type to mutant A53T alpha-synuclein at the same vector dose, both induced a similar degree of cell death. These data were supported by a biochemical analysis that showed a net increase in soluble and insoluble alpha-synuclein expression over time to the same extent for both alpha-synuclein variants.ConclusionsIn conclusion, our in vivo data provide evidence that strong and significant alpha-synuclein-induced neuropathology and progressive dopaminergic neurodegeneration can be achieved in mouse brain by means of rAAV2/7.

Highlights d Tmem106b knockout leads to LAMP1-positive vacuoles at the axon initial segment d Vacuolization is mostly confined to motoneurons d Vacuoles develop due to impaired axonal trafficking of LAMP1-positive organelles d Degradation of autophagic cargo is impaired due to TMEM106B deficiency