Purpose of Review We aim to provide quantitative evidence on the psychological impact of epidemic/pandemic outbreaks (i.e., SARS, MERS, COVID-19, ebola, and influenza A) on healthcare workers (HCWs). Recent Findings Forty-four studies are included in this review. Between 11 and 73.4% of HCWs, mainly including physicians, nurses, and auxiliary staff, reported post-traumatic stress symptoms during outbreaks, with symptoms lasting after 1-3 years in 10-40%. Depressive symptoms are reported in 27.5-50.7%, insomnia symptoms in 34-36.1%, and severe anxiety symptoms in 45%. General psychiatric symptoms during outbreaks have a range comprised between 17.3 and 75.3%; high levels of stress related to working are reported in 18.1 to 80.1%. Several individual and work-related features can be considered risk or protective factors, such as personality characteristics, the level of exposure to affected patients, and organizational support. Summary Empirical evidence underlines the need to address the detrimental effects of epidemic/pandemic outbreaks on HCWs' mental health. Recommendations should include the assessment and promotion of coping strategies and resilience, special attention to frontline HCWs, provision of adequate protective supplies, and organization of online support services.

RAB5A and RAB4 promote breast tumor cell dissemination by controlling the trafficking of proteins necessary for localized invadosome formation.

Background: The composition of the microbiome in human body sites plays an important role in health. The vaginal environment is colonized by several species of bacteria that have a major influence on reproductive health. The advancement of sequencing technologies has made the assessment of the composition of the microbiota possible through microbial DNA extraction and sequencing. Therefore, it is of a paramount importance to select a sensitive and reproducible DNA extraction method, that facilitates isolation of microbial DNA with a sufficient quantity and purity, from microbial species living in the vaginal environment. Here, we have evaluated four different DNA extraction protocols from self-collected vaginal swabs. Methods: Five healthy female volunteers were enrolled in the study. Each donor was asked to self-collect 4 samples using Copan ESwab. DNA was extracted using Qiagen DNeasy kit and three modified protocols of the MoBio PowerSoil kit (“DNeasy PowerSoil” after acquisition from Qiagen). DNA quantity and integrity was checked through Nanodrop and LabChip GX. DNA was further tested through quantitative real-time PCR (qPCR) and 16S sequencing. Vaginal microbiota diversities were determined using MiSeq-Illumina high-throughput sequencing of bacterial 16S rDNA V1–V3 fingerprint. Sequencing data were analyzed using QIIME pipeline. Results: Qiagen DNeasy protocol resulted in the highest DNA yield as compared to the modified protocols of MoBio Powersoil kit. The size of the DNA extracted using each protocol was ~40 kb. Qiagen DNeasy protocol gave the highest Genomic Quality Score (average ± standard deviation: 4.24 ± 0.36), followed by the different MoBio Powersoil protocols. A substantial variability in microbial DNA abundance was found across the protocols. The vaginal microbiota of the healthy volunteers was dominated by Lactobacillus species . MoBio Powersoil kit provided a significantly higher alpha diversity as compared to the Qiagen DNeasy kit, while beta diversity measures did not reveal any significant cluster changes, except when the Bray-Curtis method was applied. Conclusion: We were able to isolate microbial DNA from the vaginal swabs. Qiagen DNeasy method gave the highest DNA yield and quality but was not optimal in detecting microbial diversity. The modified MoBio PowerSoil protocols showed higher microbial diversities as compared to the standard protocol.

Maturity-onset diabetes of the young, MODY, is an autosomal dominant disease with incomplete penetrance. In a family with multiple generations of diabetes and several early onset diabetic siblings, we found the previously reported P33T PDX1 damaging mutation. Interestingly, this substitution was also present in a healthy sibling. In contrast, a second very rare heterozygous damaging mutation in the necroptosis terminal effector, MLKL, was found exclusively in the diabetic family members. Aberrant cell death by necroptosis is a cause of inflammatory diseases and has been widely implicated in human pathologies, but has not yet been attributed functions in diabetes. Here, we report that the MLKL substitution observed in diabetic patients, G316D, results in diminished phosphorylation by its upstream activator, the RIPK3 kinase, and no capacity to reconstitute necroptosis in two distinct MLKL−/− human cell lines. This MLKL mutation may act as a modifier to the P33T PDX1 mutation, and points to a potential role of impairment of necroptosis in diabetes. Our findings highlight the importance of family studies in unraveling MODY’s incomplete penetrance, and provide further support for the involvement of dysregulated necroptosis in human disease.

IntroductionItaly is one of the high-income countries hit hardest by Covid-19. During the first months of the pandemic, Italian healthcare workers were praised by media and the public for their efforts to face the emergency, although with limited knowledge and resources. However, healthcare workers soon had to face new challenges at a time when the national health system was working hard to recover. This study focuses on this difficult period to assess the impact of the COVID-19 pandemic on the mental health of Italian healthcare workers.Materials and MethodsHealthcare workers from all Italian regions [n = 5,502] completed an online questionnaire during the reopening phase after the first wave lockdown. We assessed a set of individual-level factors (e.g., stigma and violence against HCWs) and a set of workplace-level factors (e.g., trust in the workplace capacity to handle COVID-19) that were especially relevant in this context. The primary outcomes assessed were score ≥15 on the Patient Health Questionnaire-9 and score ≥4 on the General Health Questionnaire-12, indicators of clinically significant depressive symptoms and psychological distress, respectively. Logistic regression analyses were performed on depressive symptoms and psychological distress for each individual- and workplace-level factor adjusting for gender, age, and profession.ResultsClinically significant depressive symptoms were observed in 7.5% and psychological distress in 37.9% of HCWs. 30.5% of healthcare workers reported having felt stigmatized or discriminated, while 5.7% reported having experienced violence. Feeling stigmatized or discriminated and experiencing violence due to being a healthcare worker were strongly associated with clinically significant depressive symptoms [OR 2.98, 95%CI 2.36–3.77 and OR 4.72 95%CI 3.41–6.54] and psychological distress [OR 2.30, 95%CI 2.01–2.64 and OR 2.85 95%CI 2.16–3.75]. Numerous workplace-level factors, e.g., trust in the workplace capacity to handle COVID-19 [OR 2.43, 95%CI 1.92–3.07] and close contact with a co-worker who died of COVID-19 [OR 2.05, 95%CI 1.56–2.70] were also associated with clinically significant depressive symptoms. Similar results were found for psychological distress.ConclusionsOur study emphasizes the need to address discrimination and violence against healthcare professionals and improve healthcare work environments to strengthen the national health system's capacity to manage future emergencies.