Protective role of SARS-CoV-2 anti-S IgG against breakthrough infections among European healthcare workers during pre and post-Omicron surge-ORCHESTRA project.

PURPOSE: Anti SARS-CoV-2 vaccination initially showed high effectiveness in preventing COVID-19. However, after the surge of variants of concern, the effectiveness dropped. Several studies investigated if this was related to the decrease of the humoral response over time; however, this issue is still unclear. The aim of this study was to understand whether SARS-CoV-2 anti-S IgG levels can be used to predict breakthrough infection risk and define the timing for further booster doses administration. METHOD: Within the framework of the ORCHESTRA Project, over 20,000 health workers from 11 European centers were enrolled since December 2020. We performed two Cox proportional hazards survival analyses regarding pre-Omicron (from January to July 2021) and Omicron (December 2021-May 2022) periods. The serological response was classified as high (above the 75th percentile), medium (25th-75th), or low (< 25th). RESULTS: Seventy-four (0.33%) and 2122 (20%) health workers were infected during the first and second periods, respectively. Both Cox analyses showed that having high anti-S titer was linked to a significantly lower risk of infection as compared to having medium serological response [HR of high vs medium anti-S titer = 0.27 (95% CI 0.11-0.66) during the first phase, HR = 0.76 (95% CI 0.62-0.93) during the second phase]. CONCLUSION: Vaccine effectiveness wanes significantly after new variants surge, making anti-S titer unsuitable to predict optimal timing for further booster dose administration. Studies on other immunological indicators, such as cellular immunity, are therefore needed to better understand the mechanisms and duration of protection against breakthrough infection risk.

The Role of Physical Exercise in the Prevention of Musculoskeletal Disorders in Manual Workers: A Systematic Review and Meta-Analysis.

Work-related musculoskeletal disorders (WMSDs) are the most common occupational health problem in the European Union. Physical exercise interventions have been investigated in the prevention of WMSDs in many sectors. Therefore, our aim was to assess the effect of physical exercise in manual workers for the primary and secondary prevention of WMSDs. We conducted a systematic search of the literature and papers were included if: the participants were adult employees exclusively engaged in manual labor tasks; non-acute physical exercise intervention; pain, disability, physical functioning, or health-related quality of life outcome, with pre-post intervention measurements. We retrieved 10419 unique records and included 23 studies. A random effect meta-analysis was conducted on the studies with a control group design, using a three level model to estimate the pooled effect for pain outcomes (g = 0.4339, 95% CI : 0.1267 - 0.7412, p < 0.01), and a two-level model for disability outcomes (g = 0.6279, 95% CI : 0.3983 - 0.8575, p < 0.0001). Subset analysis revealed a moderate-to-large effect on the VAS outcome (g = 0.5866, 95% CI: 0.3102 - 0.8630, p < 0.0001). Meta-regression on pain outcomes revealed a significant effect for sex, age, study quality, and body segments tested. The analyses on all outcomes except VAS showed substantial heterogeneity (I2pain = 93%, of which 72% at the study level, I2disability = 78%, and I2vas = 56%, of which 44% at the study level). Physical exercise programs seem to have a positive effect on pain and disability stemming from WRMSDs in manual workers.

Inhibition of MMPs supports amoeboid angiogenesis hampering VEGF-targeted therapies via MLC and ERK 1/2 signaling.

BACKGROUND: In the past decades studies on anti-tumoral drugs inhibiting matrix metalloproteinase (MMPs) were disappointing. Recently, we demonstrated that mature endothelial cells (ECs) and endothelial colony forming cells (ECFCs) can switch between invasion modes to cope with challenging environments, performing the "amoeboid angiogenesis" in the absence of proteases activity. METHODS: We first set out to investigate by ELISA if the inhibitors of the main protease family involved in angiogenesis were differently expressed during breast cancer progression. We used Marimastat, a broad-spectrum MMP inhibitor, as a means of inducing amoeboid characteristics and studied VEGF role in amoeboid angiogenesis. Thus, we performed invasion and capillary morphogenesis assay, morphological, cell signaling and in vivo mouse studies. RESULTS: Our data showed that TIMP1, TIMP2, alpha2-antiplasmin, PAI-1 and cystatin increase in breast cancer serum of patients with primary cancer and lymph node positive compared to healthy women. In vitro results revealed that the most high-powered protease inhibitors able to induce amoeboid invasion of ECFCs were TIMP1, 2 and 3. Surprisingly, Marimastat promotes ECFC invasion and tubular formation in vitro and in vivo, inducing amoeboid characteristics. We observed that the combination of Marimastat plus VEGF doesn't boost neither cell invasion nor vessel formation capacity. Moreover, inhibition of VEGF activity with Bevacizumab in the presence of Marimastat confirmed that amoeboid angiogenesis is independent from the stimulus of the main vascular growth factor, VEGF. CONCLUSIONS: We underline the importance to consider the amoeboid mechanism of endothelial and cancer cell invasion, probably responsible for the failure of synthetic metalloproteinase inhibitors as cancer therapy and tumor resistance to VEGF-targeted therapies, to set-up new drugs to be used in cancer therapy.

The Long Non-coding RNA HOTAIR Controls the Self-renewal, Cell Senescence, and Secretion of Anti-aging Protein α-Klotho in Human Adult Renal Progenitor Cells.

The long non-coding RNAs (lncRNA) play an important role in several biological processes, including some renal diseases. Nevertheless, little is known about lncRNA that are expressed in the healthy kidneys and involved in renal cell homeostasis and development, and even less is known about lncRNA involved in the maintenance of human adult renal stem/progenitor cells (ARPCs) that have been shown to be very important for renal homeostasis and repair processes. Through a whole-genome transcriptome screening, we found that the HOTAIR lncRNA is highly expressed in renal progenitors and potentially involved in cell cycle and senescence biological processes. By CRISPR/Cas9 genome editing, we generated HOTAIR knockout ARPC lines and established a key role of this lncRNA in ARPC self-renewal properties by sustaining their proliferative capacity and limiting the apoptotic process. Intriguingly, the HOTAIR knockout led to the ARPC senescence and to a significant decrease in the CD133 stem cell marker expression which is an inverse marker of ARPC senescence and can regulate renal tubular repair after the damage. Furthermore, we found that ARPCs expressed high levels of the α-Klotho anti-aging protein and especially 2.6-fold higher levels compared to that secreted by renal proximal tubular cells (RPTECs). Finally, we showed that HOTAIR exerts its function through the epigenetic silencing of the cell cycle inhibitor p15 inducing the trimethylation of the histone H3K27. Altogether, these results shed new light on the mechanisms of regulation of these important renal cells and may support the future development of precision therapies for kidney diseases.

Arsenic may be a carcinogenic determinant of a subset of gallbladder cancer: A pilot study.

Gallbladder cancer (GBC) is one of the deadliest malignancy and treatment options are deplorably limited. Better strategies of prevention are urgently needed but knowledge on risk factors remains scarce. Recent data suggested that arsenic (As) may be involved in GBC carcinogenesis but the question remains debated. To date, there are no data on As measurement in GBC samples. This pilot study aimed to measure As concentrations in tissue samples from patients with GBC compared to non-cancerous gallbladder (NCGB). Included patients underwent cholecystectomy at Hospital Clinico Universidad de Chile, Santiago in Chile, a country with high As exposure, between 2001 and 2020. Tissue samples were preserved in formalin-fixed, paraffin-embedded blocks. Selected samples were retrieved, processed and submitted to inductively coupled plasma mass spectrometry (ICP-MS) to determine As concentrations. A total of 77 patients were included, including 35 GBC and 42 NCGB. The two groups were comparable, except for age (68 vs. 49 years, p < 0.001). Measured in 11 GBC and 38 NCGB, total As was detected in 5 GBC (14%) compared to 0 NCGB samples (p < 0.001). GBC group also showed higher median values of As compared to NCGB (p < 0.001). This pilot study provided a proof-of-concept to measure As concentrations in gallbladder samples and showed higher level of As in GBC samples compared to NCGB, paving the way for future studies aiming to investigate the impact of As on GBC, which may contribute to the prevention of this deadly disease.

Ceruloplasmin-Deficient Mice Show Dysregulation of Lipid Metabolism in Liver and Adipose Tissue Reduced by a Protein Replacement.

Ceruloplasmin is a ferroxidase that plays a role in iron homeostasis; its deficiency fosters inter alia iron accumulation in the liver, which expresses the soluble form of the protein secreted into the bloodstream. Ceruloplasmin is also secreted by the adipose tissue, but its role in adipocytes has been poorly investigated. We hypothesized that ceruloplasmin might have a role in iron/lipid interplay. We investigated iron/lipid dysmetabolism in the liver and adipose tissue of the ceruloplasmin-deficient mouse (CpKO) model of aceruloplasminemia and evaluated the effectiveness of ceruloplasmin replacement. We found that CpKO mice were overweight, showing adipose tissue accumulation, liver iron deposition and steatosis. In the adipose tissue of CpKO mice, iron homeostasis was not altered. Conversely, the levels of adiponectin and leptin adipokines behaved opposite to the wild-type. Increased macrophage infiltration was observed in adipose tissue and liver of CpKO mice, indicating tissue inflammation. The treatment of CpKO mice with ceruloplasmin limited liver iron accumulation and steatosis without normalizing the expression of iron homeostasis-related proteins. In the CpKO mice, the protein replacement limited macrophage infiltration in both adipose and hepatic tissues reduced the level of serum triglycerides, and partially recovered adipokines levels in the adipose tissue. These results underline the link between iron and lipid dysmetabolism in ceruloplasmin-deficient mice, suggesting that ceruloplasmin in adipose tissue has an anti-inflammatory role rather than a role in iron homeostasis. Furthermore, these data also indicate that ceruloplasmin replacement therapy may be effective at a systemic level.

Cross-Sectional Study of the Psychological Well-Being of Healthcare Workers in a Large European University Hospital after the COVID-19 Initial Wave.

BACKGROUND: The SARS-CoV-2 pandemic greatly impacted healthcare workers (HCWs) dedicated to caring for COVID-19 patients. The study was conducted in a large European hospital to study the psychological distress of HCWs engaged in COVID-19 wards in the early phase of the pandemic. METHODS: A questionnaire was sent to 1229 HCWs aimed at collecting the following information: 1) sociodemographic data; 2) depression, anxiety, and stress scales (DASS-21); 3) event impact scale (IES-R); 4) perceived stress scale (PSS); and 5) work interface analysis. The responses were collected through Google® forms and then statistically analyzed. Regardless of the outcome of the questionnaire, all subjects were offered psychological support voluntarily. RESULTS: Approximately two-thirds of the workers reported no symptoms according to the DASS-21 scales, while the IES-R and PSS scales showed 36% and 43%, respectively. There were no statistically significant differences in the levels of depression investigated through the different scales in the various occupational categories. Symptoms of anxiety, stress, and depression were more pronounced in women, while the highest stress levels were observed in the younger age groups. The highest scores were observed on the DAS-21 scales of anxiety and IES-R but not on the others. Only 51 workers, most of them with previous SARS-CoV-2 infection, sought clinical psychological counseling, and more than half received subsequent psychological support. CONCLUSIONS: Our results agree with most of the literature data that anxiety, depression, and stress are associated with gender (female), age (18-44 vs. over 55), and having cared for patients with COVID-19.

Factors Associated with SARS-CoV-2 Infection before Vaccination among European Health Care Workers.

BACKGROUND: Health care workers (HCWs) were on the frontline of the current pandemic. We aimed at identifying determinants of SARS-CoV-2 infection and the effectiveness of personal protection equipment (PPE) worn by HCWs before vaccination. METHODS: We abstracted data on SARS-CoV-2 infection based on positive PCR results and sociodemographic characteristics of 38,793 HCWs from public hospitals and public health authorities from 10 European centers. We fitted cohort-specific multivariate logistic regression models to identify determinants of infection and combined the results using random-effects meta-analyses. RESULTS: The overall prevalence of infection before vaccination among HCWs was 9.58%. Infection was associated with the presence of selected symptoms; no association was found between sociodemographic factors and increased risk of infection. The use of PPE and particularly FFP2/FFP3 masks had a different protective effect during the first and second waves of the COVID pandemic. CONCLUSIONS: The study provides evidence that mask use was the most effective PPE in preventing SARS-CoV-2 infection among HCWs.

Ovarian Stem Cells (OSCs) from the Cryopreserved Ovarian Cortex: A Potential for Neo-Oogenesis in Women with Cancer-Treatment Related Infertility: A Case Report and a Review of Literature.

Cancer treatment related infertility (CTRI) affects more than one third of young women undergoing anti-cancer protocols, inducing a premature exhaustion of the ovarian reserve. In addition to ovarian suppression by GnRHa, oocyte and cortex cryopreservation has gained interest in patients with estrogen-sensitive tumors for whom the hormonal burst to prompt the multiple follicular growth could provide a further pro-life tumor pulsing. On the other hand, cortex reimplantation implies a few drawbacks due to the unknown consistency of the follicles to be reimplanted or the risk of reintroducing malignant cells. The capability of ovarian stem cells (OCSs) from fresh ovarian cortex fragments to differentiate in vitro to mature oocytes provides a tool to overcome these drawbacks. In fact, since ovarian cortex sampling and cryopreservation is practicable before gonadotoxic treatments, the recruitment of OSCs from defrosted fragments could provide a novel opportunity to verify their suitability to be expanded in vitro as oocyte like cells (OLCs). Here, we describe in very preliminary experiments the consistency of an OSC population from a single cryopreserved ovarian cortex after thawing as well as both their viability and their suitability to be further explored in their property to differentiate in OLCs, thus reinforcing interest in stemness studies in the treatment of female CTRI.

Bi-Allelic Mutations in Zebrafish pank2 Gene Lead to Testicular Atrophy and Perturbed Behavior without Signs of Neurodegeneration.

Coenzyme A (CoA) is an essential cofactor in all living organisms, being involved in a large number of chemical reactions. Sequence variations in pantothenate kinase 2 (PANK2), the first enzyme of CoA biosynthesis, are found in patients affected by Pantothenate Kinase Associated Neurodegeneration (PKAN), one of the most common forms of neurodegeneration, with brain iron accumulation. Knowledge about the biochemical and molecular features of this disorder has increased a lot in recent years. Nonetheless, the main culprit of the pathology is not well defined, and no treatment option is available yet. In order to contribute to the understanding of this disease and facilitate the search for therapies, we explored the potential of the zebrafish animal model and generated lines carrying biallelic mutations in the pank2 gene. The phenotypic characterization of pank2-mutant embryos revealed anomalies in the development of venous vascular structures and germ cells. Adult fish showed testicular atrophy and altered behavioral response in an anxiety test but no evident signs of neurodegeneration. The study suggests that selected cell and tissue types show a higher vulnerability to pank2 deficiency in zebrafish. Deciphering the biological basis of this phenomenon could provide relevant clues for better understanding and treating PKAN.

A method for the risk assessment of biomechanical overload in hospital physiotherapists.

BACKGROUND: In physiotherapists, biomechanical overload risk assessment (RA) is particularly complex due to the tasks' variability. The present study aims to propose a new methodology, named Whole Body RA Biomechanical Overload (WB-RAMBO), to assess the risk in the activities performed by physiotherapists. METHODS: Each type of intervention was broken down into elementary operations. The risk factors (force, repetitiveness, and incongruous postures) were recorded and evaluated for each of these. For each task, the risk level was obtained by integrating the results of multiple ergonomic methods among those proposed by the international literature. To verify and validate the obtained results, we reviewed the medical records of health surveillance carried out on physiotherapists. RESULTS: From the ergonomic point of view, RA shows a situation of acceptability. The observed slight dysergonomies are diluted in the work shift and allow an optimal functional recovery of the musculoskeletal system. CONCLUSIONS: This method proposes a RA for each operation performed. A work plan subjected to such a peculiar RA can be redesigned and adapted to the company's and the hypersusceptible worker's organizational needs.

Serological response after SARS-CoV2 vaccination in healthcare workers: a multicenter study.

INTRODUCTION: Characterizing immunological response following COVID-19 vaccination is an important public health issue. The objectives of the present analysis were to investigate the proportion, level and the determinants of humoral response from 21 days to three months after the first dose in vaccinated healthcare workers (HCWs). METHODS: We abstracted data on level of anti-SARS-CoV-2 Spike antibodies (IgG) and sociodemographic characteristics of 17,257 HCWs from public hospitals and public health authorities from three centers in Northern Italy who underwent COVID-19 vaccination (average 70.6 days after first dose). We fitted center-specific multivariate regression models and combined them using random-effects meta-analyses. RESULTS: A humoral response was elicited in 99.3% of vaccinated HCW. Female sex, young age, and previous COVID-19 infection were predictors of post-vaccination antibody level, and a positive association was also detected with pre-vaccination serology level and with time between pre- and post-vaccination testing, while a decline of antibody level was suggested with time since vaccination. CONCLUSIONS: These results stress the importance of analyzing retrospective data collected via occupational health surveillance of HCWs during the COVID-19 epidemic and following vaccination. They need to be confirmed in larger series based on prospectively collected data.

Systematic review and meta-analysis of epidemiological studies on the association of occupational exposure to free crystalline silica and systemic lupus erythematosus.

OBJECTIVES: Some evidence suggests that exposure to free crystalline silica may contribute to the risk of developing SLE. A systematic search was carried out for all published epidemiological studies concerning this association. A meta-analysis was conducted on relevant studies. METHODS: We searched PubMed and EMBASE databases for original articles published from 1960 to November 2019 in any language. In addition, we also searched the reference lists of included studies manually for additional relevant articles. Finally, seven studies were included in the systematic review and six studies in the meta-analysis (four case-control and two cohort studies). The odds ratio and 95% CI were calculated using a random effect meta-analysis. RESULTS: The meta-analysis of the studies, applying a random effect model, yielded an overall odds ratio of 3.49 (95% CI, 1.24, 9.83), with I2 = 92.36% (pronounced heterogeneity). We also stratified the meta-analysis by study design; case-control studies: odds ratio 1.85 (95% CI, 0.96, 3.59) with I2 = 75.92%; and cohort studies (cases with silicosis): odds ratio 9.71 (95% CI, 1.13, 83.58) with I2 = 72.65%. CONCLUSIONS: The obtained results support the hypothesis of a possible association between occupational exposure to free crystalline silica and SLE, in particular at higher exposure levels, known to induce silicosis. The studies that have investigated this association are still scarce and the heterogeneity between the studies remains high. New studies are deemed necessary to confirm the association.

Importance of mitigation measures for hospital transmission of SARS-CoV-2 at the onset of the epidemic: the experience of Brescia, Northern Italy.

PURPOSE: Since the first Italian case of SARS-CoV-2 was detected in Lombardy (Northern Italy)  Italy quickly became one of the worst-affected European countries, with a severe impact on health-care workers (HCWs). In the first epidemic, HCWs accounted for 12% of all national COVID-19 cases. We evaluated the burden of COVID-19 among HCWs and other non-health-care workers (nHCWs) in a large Italian hospital. METHODS: From March 1st to May 31st 2020, we performed a retrospective study at ASST Civil Hospital, in the Province of Brescia, Lombardy. The study population included all hospital personnel (n = 9265), categorized by professional status. RESULTS: A SARS-CoV-2 test was performed in 3572 workers (38.5%), with a positive result in 552 (5.9% of all hospital personnel). The temporal trend of SARS-CoV-2 cases in hospital staff broadly reflected that in the community, with a great majority of infections occurred during March 2020 (87.7%). From April onward, a steep decrease of positive cases was observed among hospital personnel, while in the community the decrease was much slower. Medical doctors (8.9%) and nurses (8.5%) were the most affected professional categories with a significantly higher risk of SARS-CoV-2 infection (OR 1.436 and OR 1.410, respectively p < 0.0001). HCWs in COVID-19 units presented a significantly higher risk of infection compared to HCWs in non-COVID units (p < 0.001). CONCLUSION: HCWs were severely affected by the COVID-19 epidemic, probably associated with an overwhelming burden of work and lack of preparedness in prevention of nosocomial transmission of the infection. The rapid decrease of COVID-19 spread in the hospital, registered before the one in the community, suggests that the adopted preventive measures were effective.

COVID19 outbreak in Lombardy, Italy: An analysis on the short-term relationship between air pollution, climatic factors and the susceptibility to SARS-CoV-2 infection.

Short-term exposure to air pollution, as well as to climate variables have been linked to a higher incidence of respiratory viral diseases. The study aims to assess the short-term influence of air pollution and climate on COVID19 incidence in Lombardy (Italy), during the early stage of the outbreak, before the implementation of the lockdown measures. The daily number of COVID19 cases in Lombardy from February 25th to March 10th, 2020, and the daily average concentrations up to 15 days before the study period of particulate matter (PM10, PM2.5), O3, SO2, and NO2 together with climate variables (temperature, relative humidity - RH%, wind speed, precipitation), were analyzed. A univariable mixed model with a logarithm transformation as link function was applied for each day, from 15 days (lag15) to one day (lag1) before the day of detected cases, to evaluate the effect of each variable. Additionally, change points (Break Points-BP) in the relationship between incident cases and air pollution or climatic factors were estimated. The results did not show a univocal relationship between air quality or climate factors and COVID19 incidence. PM10, PM2.5 and O3 concentrations in the last lags seem to be related to an increased COVID19 incidence, probably due to an increased susceptibility of the host. In addition, low temperature and low wind speed in some lags resulted associated with increased daily COVID19 incidence. The findings observed suggest that these factors, in particular conditions and lags, may increase individual susceptibility to the development of viral infections such as SARS-CoV-2.

Cryopreservation of adipose tissue with and without cryoprotective agent addition for breast lipofilling: A cytological and histological study.

In the second reconstructive phase of the breast after mastectomy, lipofilling is often necessary. Currently, lipofilling occurs immediately after autologous adipose tissue harvesting procedure, but most of the patients, usually, require multiple sessions to obtain a satisfactory result. Therefore, the need of repeated surgical harvesting outputs implies high risk of patients' morbidity and discomfort as well as increasing medical time and costs. The aim of our pilot study was to find out a feasible method to cryopreserve adipose tissue, in order to avoid reiterated liposuctions. Lipoaspirates samples have been harvested from 10 women and preserved by three methods: (1) the first one, using 10% Me2SO and 20% human albumin from human plasma as cryoprotective agents; (2) the second one, adding 5% Me2SO as cryoprotective agent; 3) the last one, without any cryoprotective agent. Fresh and cryopreserved fat samples, obtained through the aforementioned processes, have been analyzed ex vivo. The efficiency of the cryopreservation methods used was determined by adipocyte viability and the expression of adipocytes surface markers. Lipoaspirates stored at -196 °C for 3 months, after thawing, retained comparable adipocyte viability and histology to fresh tissue and no significant differences were found between the three methods used. Although the current results, differences between the methodologies in terms of viability may not become evident until breast lipofilling using frozen-thawed cryopreserved tissue.

Early signs of pneumoconiosis in a dental technician in Italy: a case report.

BACKGROUND: Dental technicians are at high risk of pneumoconiosis, usually driven by inhalation of mixed dusts, including metals. An etiological diagnosis is not easy to be performed, particularly in advanced stages. CASE PRESENTATION: We describe the case of an early pneumoconiosis occurring in a 47-year-old dental technician who developed respiratory symptoms shortly after beginning work. She described the work environment as dusty and lacking relevant primary prevention tools. A chest CT showed multiple peripheral pseudonodular lesions in both lower lobes; bronchoalveolar lavage and bronchial aspirate evidenced numerous macrophages with reflective metal bodies included into the cytoplasm, that at scanning electron microscopy coupled to Energy Dispersive X-Ray Analysis resulted Zirconium and Aluminum, whereas Tungsten (W) was localized outside cells. End of shift urinary concentrations of W were substantially raised as compared to pre-shift (1.1 vs. 0.2 µg/L). CONCLUSIONS: We concluded for diagnosis of early work-related pneumoconiosis due to abnormal occupational exposure to metals. The case demonstrates the need also for dental professionals to comply with industrial hygiene standards and to be monitored by occupational health physicians.

Effectiveness of BNT162b2 vaccine against SARS-CoV-2 among healthcare workers.

BACKGROUND:  The present study was aimed at evaluating the effectiveness of BNT162b2 among HCWs of a university hospital while a recrudescence of pandemics was hitting the province, with a high rate of the B.1.1.7 variant. Methods: The study was performed in the context of health surveillance at the workplaces. We monitored the SARS-CoV-2 infection and COVID-19 symptoms among HCWs classified by having received the entire vaccine schedule or not; the latter further classified in not vaccinated workers and workers who had received the first shot more than 14 days earlier. The SARS-CoV-2 infection was diagnosed by conventional RT-PCR on rhino-pharyngeal swabs, followed by gene sequencing in positive vaccinated HCWs. The cumulative incidence of infections in the period was normalised to 100,000 people. Results: At the end of the observation period, HCWs that had completed the full schedule were at lower infection risk than both unvaccinated HCWs and the workforce who had not yet gained the complete theoretical protection from the vaccine (by 2.4-folds). Overall, ninety-two SARS-CoV-2 infections were observed among HCWs, mostly among not protected workers (52 cases) but none of them showed symptoms requiring hospitalisation. Conclusions: The vaccination campaign effectively reduced the appearance of symptoms and the incidence of infections among vaccinated HCWs. Among vaccinated HCWs, gene sequencing was possible in five cases only, 4 B.1.1.7 and 1 B1.525 variants. The high rate of unsuccessful gene sequencing observed among infected vaccinated workers could be explained by a low viral burden. Vaccination for COVID-19 should be mandatory in occupational settings with a high infective risk.

Renal progenitor cells revert LPS-induced endothelial-to-mesenchymal transition by secreting CXCL6, SAA4, and BPIFA2 antiseptic peptides.

Endothelial dysfunction is a hallmark of LPS-induced acute kidney injury (AKI). Endothelial cells (ECs) acquired a fibroblast-like phenotype and contributed to myofibroblast generation through the endothelial-to-mesenchymal transition (EndMT) process. Of note, human adult renal stem/progenitor cells (ARPCs) enhance the tubular regenerative mechanism during AKI but little is known about their effects on ECs. Following LPS exposure, ECs proliferated, decreased EC markers CD31 and vascular endothelial cadherin, and up-regulated myofibroblast markers, collagen I, and vimentin. The coculture with ARPCs normalized the EC proliferation rate and abrogated the LPS-induced EndMT. The gene expression analysis showed that most of the genes modulated in LPS-stimulated ARPCs belong to cell activation and defense response pathways. We showed that the ARPC-specific antifibrotic effect is exerted by the secretion of CXCL6, SAA4, and BPIFA2 produced after the anaphylatoxin stimulation. Next, we investigated the molecular signaling that underlies the ARPC protective mechanism and found that renal progenitors diverge from differentiated tubular cells and ECs in myeloid differentiation primary response 88-independent pathway activation. Finally, in a swine model of LPS-induced AKI, we observed that activated ARPCs secreted CXCL6, SAA4, and BPIFA2 as a defense response. These data open new perspectives on the treatment of both sepsis- and endotoxemia-induced AKI, suggesting an underestimated role of ARPCs in preventing endothelial dysfunction and novel strategies to protect the endothelial compartment and promote kidney repair.-Sallustio, F., Stasi, A., Curci, C., Divella, C., Picerno, A., Franzin, R., De Palma, G., Rutigliano, M., Lucarelli, G., Battaglia, M., Staffieri, F., Crovace, A., Pertosa, G. B., Castellano, G., Gallone, A., Gesualdo, L. Renal progenitor cells revert LPS-induced endothelial-to-mesenchymal transition by secreting CXCL6, SAA4, and BPIFA2 antiseptic peptides.

Occupational exposure to carbon fibers impregnated with epoxy resins and evaluation of their respirability.

Objectives: The study aims to investigate occupational exposure to carbon fibers impregnated with epoxy resins (carbon fiber reinforced [CFR]) in workers at an airplane fuselage section construction plant, by environmental and biological monitoring.Materials and methods: Determination of airborne CFR was done by environmental sampling with active samplers, 11 of which were stationary and 19 personal samplings. The subsequent analyses were performed in the scanning electron microscope fitted with an X-ray microanalysis system (SEM-EDXA). Biological monitoring was carried out by determining CFR in exhaled breath condensate (EBC) collected from 19 male workers who wore personal environmental samplers (exposed workers) and from 10 male workers at the same factory who had no occupational exposure to CFR (internal controls). CFR analysis was done by SEM, applying the method used for determining asbestos fibers in aqueous samples.Results: The airborne CFR concentrations were found to be significantly higher (p = 0.03) at personal samplings (median value 7.01 ff/L, range 1.24-11.16 ff/L) than stationary samplings (median value 1.93 ff/L, range 0.55-10.09 ff/L). The aerodynamic diameters calculated starting from the length and geometric diameter of the sampled CFRs were always higher than 20 µm. CFR was not found in any of the EBC samples collected from the exposed workers and controls.Conclusions: Despite the evidence of occupational exposure to low concentrations of CFR, the absence of such fibers in the EBC in the exposed workers confirms their non-respirability, as expected based on their aerodynamic diameter.