Redox biomarkers in asymptomatic latent human tuberculosis: a comparison with active disease.

BACKGROUND: The latent TB infection (LTBI) is an asymptomatic infection caused by Mycobacterium tuberculosis (M.bt). Previous studies have shown a host-protective role for Heme oxygenase-1 (HO-1) during Mtb infection and an important involvement of Glutathione peroxidase-4 (Gpx4) in the necrotic pathology of the disease. Furthermore, increasing evidence suggested a crucial role for Glutathione in the granulomatous response to M. tb infection, with altered GSH levels associated to decreased host resistance. The aim of this study was to provide additional tools for discriminating the pathologic TB state and the asymptomatic infection. METHODS: We analyzed the gene expression of HO-1 and Gpx4 enzymes in blood of subjects with LTBI, active TB and healthy controls, and we also measured blood levels of the reduced (GSH) and oxidized (GSSG) forms of glutathione, together with the evaluation of GCL expression, the gene responsible for the GSH de novo synthesis. RESULTS: Our findings highlight a shift of glutathione homeostasis towards a more reducing conditions in LTBI, and a different modulation of GSH-dependent genes and HO-1 expression respect to active TB. CONCLUSION: This study can provide useful tools to understand the redox background that address the infection toward the asymptomatic or active disease.

General work stress and suicide cognitions in health-care workers: mediating effect of hopelessness and job satisfaction.

Individuals with a satisfactory level of job satisfaction are much less likely to feel hopeless about their future and are more likely to perform efficiently in the workplace. General work stress (i.e., the work-related stress subjectively experienced) is a significant predictor of suicide cognitions. Furthermore, it has been posited that satisfaction and hope are fundamental to life from an existential perspective. We, therefore, tested a hypothetical model of general work stress, suicide cognitions, hopelessness, and job satisfaction. The data were collected from 416 health-care workers through a convenience sampling method. The mediation analysis results revealed significant negative and positive relationships among general work stress, suicide conceptions, hopelessness, and job satisfaction. The findings indicate that hopelessness and job satisfaction have a parallel mediating effect in the relationship between general work stress and suicide cognitions. The result of the study is of great importance, which suggests that interventions to alleviate hopelessness and work stress and to boost the job satisfaction of medical staff may help prevent suicide cognitions.

Association between sex hormones and anti-S/RBD antibody responses to COVID-19 vaccines in healthcare workers.

Healthcare workers (HCWs) are the target population for vaccination against coronavirus disease (COVID-19) as they are at a high risk of exposure and transmission of pathogens to patients. Neutralizing antibodies developed after COVID-19 vaccination decline within few months of vaccination. Several factors, including age and sex, can affect the intensity, efficacy, and duration of immune response to vaccines. However, sex-specific analyses of humoral responses to COVID-19 vaccines are lacking. This study aimed to evaluate sex-based differences in anti-S/RBD (Receptor Binding Domain) responses at three different time points after the second dose of mRNA COVID-19 vaccine in HCWs in relation to age, and to investigate the role of sex hormones as potential markers of response. Anti-S/RBD levels after two doses of the mRNA vaccine were collected from 521 HCWs naïve to COVID-19, working at two Italian Clinical Centers. Multiple regression analysis was applied to evaluate the association between anti-S levels and sex, age, and plasma levels of sex hormones. Significantly higher anti-S/RBD response to the COVID-19 vaccination was found in female HCWs, and a significant and more abrupt decline in response with time was observed in women than that in men. A novel, positive association of testosterone plasma levels and higher anti-S levels in male HCWs was found, suggesting its potential role as sex specific marker in males. In conclusion, understanding the sex-based differences in humoral immune responses to vaccines may potentially improve vaccination strategies and optimize surveillance programs for HCWs.

Feasibility of a Stop Smoking Program for Healthcare Workers in an Italian Hospital: Econometric Analysis in a Total Worker Health® Approach.

Background: Over 20% of healthcare workers (HCWs) are active smokers. Smoking is a targeted issue for workplace health promotion (WHP) programs. Objective: Our study aims to evaluate the effectiveness of the Stop Smoking Promotion (SSP) intervention, a 6-hour training course for HCWs, which took place from May 2018 to July 2019. Methods: We compared HCWs who successfully quit smoking (n = 15) to those who did not (n = 25) in terms of Sickness Absence Days (SADs). Moreover, we conducted an econometric analysis by calculating the return on investment and implementing a break-even analysis. Findings: Among the 40 enrolled workers, a success rate of 37.5% was observed after a span of over two years from the SSP intervention (with nurses and physicians showed the best success rate). Overall, participants showed a noticeable absenteeism reduction after the SSP intervention, with a reduction rate of 85.0% in a one-year period. The estimated ROI for the hospital was 1.90, and the break-even point was 7.85. In other words, the organization nearly doubled its profit from the investment, and the success of at least eight participants balanced costs and profits. Conclusion: Our pilot study confirms that WHP programs are simple and cost-saving tools which may help improve control over the smoking pandemic in healthcare settings.

Vaccinating Welders against Pneumococcus: Evidence from a Systematic Review and Meta-Analysis.

Workers occupationally exposed to welding dusts and fumes have been suspected to be at increased risk of invasive pneumococcal disease (IPD). Since the 2010s, the United Kingdom Department of Health and the German Ständige Impfkommission (STIKO) actively recommend welders undergo immunization with the 23-valent polysaccharide (PPV23) pneumococcal vaccine, but this recommendation has not been extensively shared by international health authorities. The present meta-analysis was therefore designed to collect available evidence on the occurrence of pneumococcal infection and IPD among welders and workers exposed to welding fumes, in order to ascertain the effective base of evidence for this recommendation. PubMed, Embase and MedRxiv databases were searched without a timeframe restriction for the occurrence of pneumococcal infections and IPD among welders and workers exposed to metal dusts, and articles meeting the inclusion criteria were included in a random-effect meta-analysis model. From 854 entries, 14 articles (1.6%) underwent quantitative analysis, including eight retrospective studies (publication range: 1980-2010), and six reports of professional clusters in shipbuilding (range: 2017-2020). Welders had an increased likelihood of developing IPD compared with non-welders (odds ratio 2.59, 95% CI 2.00-3.35, I2 = 0%, p = 0.58), and an increased likelihood of dying from IPD (standardized mortality ratio (SMR) 2.42, 95% CI 1.96-2.99, I2 = 0%, p = 0.58). Serotype typing was available for 72 cases, 60.3% of which were represented by serotype 4, followed by 12F (19.2%) and serotype 8 (8.2%). Although the available data derive from a limited number of studies, available results suggest that pneumococcal vaccination should be recommended for workers exposed to welding fumes, and vaccination strategies should consider the delivery of recombinant formulates in order to combine the direct protection against serotypes of occupational interest with the mucosal immunization, reducing the circulation of the pathogen in occupational settings characterized by close interpersonal contact.

Nurse burnout before and during the COVID-19 pandemic: a systematic comparative review.

Introduction: This review aimed to compare available evidence examining burnout using the Maslach Burnout Inventory (MBI) in nurses before and during the COVID-19 pandemic. The specific objective was to compare nurse burnout scores in terms of emotional exhaustion, depersonalization, and personal accomplishment. Methods: A comprehensive search was conducted for studies on nurses' burnout using the MBI published between 1994 and 2022. In total, 19 studies conducted prior to the pandemic and 16 studies conducted during the pandemic were included and compared using the criteria from the Joanna Briggs Institute Critical Appraisal Tool. Results: Surprisingly, the results indicated that nurses' burnout scores did not differ significantly before (N = 59,111) and during (N = 18,629) the pandemic. The difference observed was qualitative rather than quantitative. Discussion: The outbreak of the COVID-19 pandemic exacerbated an already critical situation, and while COVID-19 may serve as an additional triggering factor for staff mental illness, it cannot solely explain the observed burnout levels. These findings underscore the need for long-term clinical and preventive psychological interventions, suggesting that psychological resources should not be limited to emergencies but extended to address the ongoing challenges faced by nurses. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=399628, identifier: CRD42023399628.

Functional CVIDs phenotype clusters identified by the integration of immune parameters after BNT162b2 boosters.

Introduction: Assessing the response to vaccinations is one of the diagnostic criteria for Common Variable Immune Deficiencies (CVIDs). Vaccination against SARS-CoV-2 offered the unique opportunity to analyze the immune response to a novel antigen. We identify four CVIDs phenotype clusters by the integration of immune parameters after BTN162b2 boosters. Methods: We performed a longitudinal study on 47 CVIDs patients who received the 3rd and 4th vaccine dose of the BNT162b2 vaccine measuring the generation of immunological memory. We analyzed specific and neutralizing antibodies, spike-specific memory B cells, and functional T cells. Results: We found that, depending on the readout of vaccine efficacy, the frequency of responders changes. Although 63.8% of the patients have specific antibodies in the serum, only 30% have high-affinity specific memory B cells and generate recall responses. Discussion: Thanks to the integration of our data, we identified four functional groups of CVIDs patients with different B cell phenotypes, T cell functions, and clinical diseases. The presence of antibodies alone is not sufficient to demonstrate the establishment of immune memory and the measurement of the in-vivo response to vaccination distinguishes patients with different immunological defects and clinical diseases.

Hydroxytyrosol Recovers SARS-CoV-2-PLpro-Dependent Impairment of Interferon Related Genes in Polarized Human Airway, Intestinal and Liver Epithelial Cells.

The SARS-CoV-2 pandemic has caused approximately 6.3 million deaths, mainly due to the acute respiratory distress syndrome or multi-organ failure that characterizes COVID-19 acute disease. Post-acute COVID-19 syndrome, also known as long-COVID, is a condition characterized by a complex of symptoms that affects 10-20% of the individuals who have recovered from the infection. Scientific and clinical evidence demonstrates that long-COVID can develop in both adults and children. It has been hypothesized that multi-organ effects of long-COVID could be associated with the persistence of virus RNA/proteins in host cells, but the real mechanism remains to be elucidated. Therefore, we sought to determine the effects of the exogenous expression of the papain-like protease (PLpro) domain of the non-structural protein (NSP3) of SARS-CoV-2 in polarized human airway (Calu-3), intestinal (Caco-2), and liver (HepG2) epithelial cells, and to evaluate the ability of the natural antioxidant hydroxytyrosol (HXT) in neutralizing these effects. Our results demonstrated that PLpro was able to induce a cascade of inflammatory genes and proteins (mainly associated with the interferon pathway) and increase the apoptotic rate and expression of several oxidative stress markers in all evaluated epithelial cells. Noteably, the treatment with 10 µM HXT reverted PL-pro-dependent effects almost completely. This study provides the first evidence that SARS-CoV-2 PLpro remaining in host cells after viral clearance may contribute to the pathogenetic mechanisms of long-COVID. These effects may be counteracted by natural antioxidants. Further clinical and experimental studies are necessary to confirm this hypothesis.

When a Neglected Tropical Disease Goes Global: Knowledge, Attitudes and Practices of Italian Physicians towards Monkeypox, Preliminary Results.

Monkeypox (MPX) has been regarded as a neglected tropic disease of Western and Central Africa since the early 70s. However, during May 2022, an unprecedent outbreak of MPX has involved most of European Countries, as well as North and South America. While the actual extent of this outbreak is being assessed by health authorities, we performed a pilot study on specific knowledge, attitudes, and practices (KAP) in a sample of Italian medical professionals (24-30 May 2022; 10,293 potential recipients), focusing on Occupational Physicians (OP), Public Health Professionals (PH), and General Practitioners (GP), i.e., medical professionals more likely involved in the early management of incident cases. More specifically, we inquired into their attitude on the use of variola vaccine in order to prevent MPX infection. From a total of 566 questionnaire (response rate of 5.5%), 163 participants were included in the final analyses. Knowledge status was quite unsatisfying, with substantial knowledge gaps on all aspect of MPX. In turn, analysis of risk perception suggested a substantial overlooking of MPX as a pathogen, particularly when compared to SARS-CoV-2, TB, HIV, and HBV. Overall, 58.6% of respondents were somehow favorable to implement variola vaccination in order to prevent MPX, and the main effectors of this attitude were identified in having been previously vaccinated against seasonal influenza (adjusted Odds Ratio [aOR] 6.443, 95% Confidence Interval [95%CI] 1.798-23.093), and being favorable to receive variola vaccine (aOR 21.416; 95%CI 7.290-62.914). In summary, the significant extent of knowledge gaps and the erratic risk perception, associated collectively stress the importance of appropriate information campaigns among first-line medical professionals.

Managing of Migraine in the Workplaces: Knowledge, Attitudes and Practices of Italian Occupational Physicians.

Background and Objectives: Migraine is a debilitating disorder, whose incidence peak in the age group of 30-39 years overlaps with the peak of employment years, potentially representing a significant issue for occupational physicians (OP). The present study was performed in order to characterize their knowledge, attitudes and practices on migraine in the workplaces. Materials and Methods: A convenience sample of 242 Italian OP (mean age 47.8 ± 8.8 years, males 67.4%) participated in an internet-based survey by completing a structured questionnaire. Results: Adequate general knowledge of migraine was found in the majority of participants. Migraine was identified as a common and severe disorder by the majority of respondents (54.0% and 60.0%). Overall, 61.2% of participants acknowledged migraine as difficult to manage in the workplace, a status that made it more likely for OP understanding its potential frequency (Odds Ratio [OR] 3.672, 95% confidence interval [95%CI] 1.526-8.831), or reported previous managing of complicated cases requiring conditional fitness to work judgement (OR 4.761, 95%CI 1.781-2.726). Moreover, professionals with a qualification in occupational medicine (OR 20.326, 95%CI 2.642-156.358), acknowledging the difficult managing of migraine in the workplaces (OR 2.715, 95%CI 1.034-7.128) and having received any request of medical surveillance for migraine (OR 22.878, 95%CI 4.816-108.683), were more likely to recommend specific requirements for migraineur workers. Conclusions: Migraine was recognized as a common disorder, but also as a challenging clinical problem for OP. Participating OP exhibited a substantial understanding of migraine and its triggers, but residual false beliefs and common misunderstanding may impair the proper management of this disorder, requiring improved and specifically targeted interventions.

Case Report: Precision COVID-19 Immunization Strategy to Overcome Individual Fragility: A Case of Generalized Lipodystrophy Type 4.

A 48-year-old patient affected with congenital generalized lipodystrophy type 4 failed to respond to two doses of the BNT162b2 vaccine, consisting of lipid nanoparticle encapsulated mRNA. As the disease is caused by biallelic variants of CAVIN1, a molecule indispensable for lipid endocytosis and regulation, we complemented the vaccination cycle with a single dose of the Ad26.COV2 vaccine. Adenovirus-based vaccine entry is mediated by the interaction with adenovirus receptors and transport occurs in clathrin-coated pits. Ten days after Ad26.COV2 administration, S- and RBD-specific antibodies and high-affinity memory B cells increased significantly to values close to those observed in Health Care Worker controls.

Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections.

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.

The Management of Workplace Violence against Healthcare Workers: A Multidisciplinary Team for Total Worker Health® Approach in a Hospital.

The risk of aggression against healthcare workers (HCWs) is a globally well-known topic. However, workplace violence (WV) is often considered as part of HCW's job, leading to a general underreporting. This cross-sectional study aims at providing a descriptive analysis of aggressive acts against HCWs registered in a 34-month period in a pediatric hospital. According to a specific protocol, each aggressive act was analyzed by a multidisciplinary team using the "Modified Overt Aggression Scale" (MOAS), the "General Health Questionnaire-12" (GHQ-12), and the "Short Form-36 Health Survey" (SF-36) to build a report addressing improvement measures. A three-domain model of WV was also developed considering: (1) assaulted HCWs, (2) attacker-related issues, and (3) environmental context. Contributing factors to overt aggression were outlined and tested using univariate analyses. Statistically significant factors were then included in a multiple linear regression model. A total of 82 aggressive acts were registered in the period. MOAS scores registered a mean value of 3.71 (SD: 4.09). Verbal abuse was the most common form of WV. HCWs professional category, minor psychiatric disorder, emotional role limitation, type of containment used, and emotion intensity were significantly associated with overt aggression (p < 0.05), as well as the attacker's role in the hospital (p < 0.05). The multiple regression analysis confirmed these findings (p < 0.001). Raising awareness on the aggression risk and contributing factors may lead to a relevant improvement of workplace environment, individual workers' health, and organizational well-being.

Personalized profiles of antioxidant signaling pathway in patients with tuberculosis.

BACKGROUND/PURPOSE: The non-protein thiol glutathione is protective against infection by Mycobacterium tuberculosis (MTB) and, together with the transcription factor NRF2 (the nuclear factor erythroid 2-related factor 2), plays a crucial role in counteracting MTB-induced redox imbalance. Many genes implicated in the antioxidant response belong to the NRF2-signalling pathway, whose central role in the pathogenesis of tuberculosis (TB) has been recently proposed. METHODS: In this study, we measured GSH levels in blood of patients with active TB and analysed the individual NRF2-mediated redox profile, in order to provide additional tools for discriminating the pathologic TB state and addressing therapeutic interventions. RESULTS: Our findings show a systemic individual modulation of GSH and NRF2 signaling pathway in patients with TB, with a "personalized" induction of NRF2-target genes. CONCLUSION: This study can provide useful tools to monitor the course of the infection and address patients' treatment.

Subjective Symptoms in Magnetic Resonance Imaging Personnel: A Multi-Center Study in Italy.

Introduction: Magnetic Resonance Imaging (MRI) personnel have significant exposure to static and low-frequency time-varying magnetic fields. In these workers an increased prevalence of different subjective symptoms has been observed. The aim of our study was to investigate the prevalence of non-specific subjective symptoms and of "core symptoms" in a group of MRI personnel working in different centers in Italy, and of possible relationships with personal and occupational characteristics. Methods: The occurrence of 11 subjective symptoms was evaluated using a specific questionnaire with 240 subjects working in 6 different Italian hospitals and research centers, 177 MRI health care and research personnel and 63 unexposed subjects employed in the same departments. Exposure was subjectively investigated according to the type of MRI scanner (≤1.5 vs. ≥3 T) and to the number of MRI procedures attended and/or performed by the personnel, even if no information on how frequently the personnel entered the scanner room was collected. The possible associations among symptoms and estimated EMF exposure, the main characteristics of the population, and job stress perception were analyzed. Results: Eighty-six percent of the personnel reported at least one symptom; drowsiness, headache, and sleep disorders were the most frequent. The total number of symptoms did not differ between exposed persons and controls. Considering the total number of annual MRI procedures reported by the personnel, no significant associations were found nor with the total number of symptoms, nor with "core symptoms." Only subjects complaining of drowsiness also reported a significantly higher mean annual number of MRI procedures with ≤ 1.5 T scanners when compared with exposed subjects without drowsiness. In a multivariate model, subjects with a high level of perceived stress complained of more symptoms (p = 0.0002). Conclusions: Our study did not show any association between the occurrence of reversible subjective symptoms, including the more specific "core symptoms," and the occupational exposure of MRI personnel to static and low-frequency time-varying magnetic fields. On the other hand, the role played by occupational stress appears to be not negligible. In further research in this field, measurements of EMF exposure should be considered.

SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best.

BACKGROUND: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. METHODS: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. RESULTS: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. CONCLUSION: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected.

Humoral and Cellular Response Following Vaccination With the BNT162b2 mRNA COVID-19 Vaccine in Patients Affected by Primary Immunodeficiencies.

Mass SARS-Cov-2 vaccination campaign represents the only strategy to defeat the global pandemic we are facing. Immunocompromised patients represent a vulnerable population at high risk of developing severe COVID-19 and thus should be prioritized in the vaccination programs and in the study of the vaccine efficacy. Nevertheless, most data on efficacy and safety of the available vaccines derive from trials conducted on healthy individuals; hence, studies on immunogenicity of SARS-CoV2 vaccines in such populations are deeply needed. Here, we perform an observational longitudinal study analyzing the humoral and cellular response following the BNT162b2 mRNA COVID-19 vaccine in a cohort of patients affected by inborn errors of immunity (IEI) compared to healthy controls (HC). We show that both IEI and HC groups experienced a significant increase in anti-SARS-CoV-2 Abs 1 week after the second scheduled dose as well as an overall statistically significant expansion of the Ag-specific CD4+CD40L+ T cells in both HC and IEI. Five IEI patients did not develop any specific CD4+CD40L+ T cellular response, with one of these patients unable to also mount any humoral response. These data raise immunologic concerns about using Ab response as a sole metric of protective immunity following vaccination for SARS-CoV-2. Taken together, these findings suggest that evaluation of vaccine-induced immunity in this subpopulation should also include quantification of Ag-specific T cells.