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Objectives Workers in the construction industry have been exposed to asbestos in various occupations. In Italy, a National Mesothelioma Registry has been implemented more than 20 years ago. Using cases selected from this registry and exploiting existing control data sets, we estimated relative risks for pleural mesothelioma (PM) among construction workers.Design Case–control study.Setting Cases from the National Mesothelioma Registry (2000–2018), controls from three previous case–control studies.Methods We selected male PM incident cases diagnosed in 2000–2018. Population controls were taken from three studies performed in six Italian regions within two periods (2002–2004 and 2012–2016). Age-adjusted and period-adjusted unconditional logistic regression models were fitted to estimate odds ratios (OR) for occupations in the construction industry. We followed two approaches, one (primary) excluding and the other (secondary) including subjects employed in other non-construction blue collar occupations for >5 years. For both approaches, we performed an overall analysis including all cases and, given the incomplete temporal and geographic overlap of cases and controls, three time or/and space restricted sensitivity analyses.Results The whole data set included 15 592 cases and 2210 controls. With the primary approach (4797 cases and 1085 controls), OR was 3.64 (2181 cases) for subjects ever employed in construction. We found elevated risks for blue-collar occupations (1993 cases, OR 4.52), including bricklayers (988 cases, OR 7.05), general construction workers (320 cases, OR 4.66), plumbers and pipe fitters (305 cases, OR 9.13), painters (104 cases, OR 2.17) and several others. Sensitivity analyses yielded very similar findings. Using the secondary approach, we observed similar patterns, but ORs were remarkably lower.Conclusions We found markedly increased PM risks for most occupations in the construction industry. These findings are relevant for compensation of subjects affected with mesothelioma in the construction industry.

Introduction: This study described the degenerative changes and infection patterns of the pulp tissue associated with symptomatic irreversible pulpitis., Methods: The material consisted of 32 extracted teeth with untreated deep caries that were clinically and histologically diagnosed with irreversible pulpitis and were part of the histopathologic collection of 1 of the authors. The controls consisted of intact teeth with normal uninflamed pulps and teeth with reversible pulpitis. Teeth were processed for histopathologic and histobacteriologic analyses., Results: All teeth with irreversible pulpitis showed areas of severe acute inflammation, necrosis, microabscesses, and bacterial infection in the pulp chamber. These areas were surrounded by a chronic inflammatory infiltrate, and, at the distance, the pulp tissue was often uninflamed. Bacteria were also observed in the areas surrounding the necrotic foci, both as scattered cells through the extravascular space and at varying numbers within the blood vessel lumen. The number of bacteria and the density of the intravascular bacterial aggregations varied considerably. In one third of the cases, bacteria occurred in the lumen of venules in areas at a considerable distance from the necrotic focus in the coronal third of the root. No intravascular bacteria were noted in the middle and apical segments of the canal. No bacteria were found in the pulps of any of the control specimens., Conclusions: Bacterial invasion and colonization of necrotic areas were observed in the pulp of all teeth with caries exposure and symptomatic irreversible pulpitis. Bacterial penetration of blood vessels occurred in all cases, suggesting that this may be an important mechanism of spread of bacterial infection through the pulp tissue in an endodontic infection., (Copyright © 2021 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: The onset of drug resistance is a major cause of treatment failure in multiple myeloma. Although increasing evidence is defining the role of miRNAs in mediating drug resistance, their potential activity as drug-sensitizing agents has not yet been investigated in multiple myeloma., Experimental Design: Here we studied the potential utility of miR-221/222 inhibition in sensitizing refractory multiple myeloma cells to melphalan., Results: miR-221/222 expression inversely correlated with melphalan sensitivity of multiple myeloma cells. Inhibition of miR-221/222 overcame melphalan resistance and triggered apoptosis of multiple myeloma cells in vitro, in the presence or absence of human bone marrow (BM) stromal cells. Decreased multiple myeloma cell growth induced by inhibition of miR-221/222 plus melphalan was associated with a marked upregulation of pro-apoptotic BBC3/PUMA protein, a miR-221/222 target, as well as with modulation of drug influx-efflux transporters SLC7A5/LAT1 and the ABC transporter ABCC1/MRP1. Finally, in vivo treatment of SCID/NOD mice bearing human melphalan-refractory multiple myeloma xenografts with systemic locked nucleic acid (LNA) inhibitors of miR-221 (LNA-i-miR-221) plus melphalan overcame drug resistance, evidenced by growth inhibition with significant antitumor effects together with modulation of PUMA and ABCC1 in tumors retrieved from treated mice., Conclusions: Taken together, our findings provide the proof of concept that LNA-i-miR-221 can reverse melphalan resistance in preclinical models of multiple myeloma, providing the framework for clinical trials to overcome drug resistance, and improve patient outcome in multiple myeloma., (©2015 American Association for Cancer Research.)

Background & Aim: The miR-221/222 cluster is upregulated in malignant plasma cells from multiple myeloma (MM) patients harboring the t(4;14) translocation. We previously reported that silencing of miR-221/222 by an antisense oligonucleotide induces anti-MM activity and upregulates canonical miR-221/222 targets. The in vivo anti-tumor activity occurred when miR-221/222 inhibitors were delivered directly into MM xenografts. The aim of the present study was to evaluate the anti-MM activity of a novel phosphorothioate modified backbone 13-mer locked nucleic acid (LNA)-Inhibitor-miR-221 (LNA-i-miR-221) specifically designed for systemic delivery., Methods: In vitro anti-MM activity of LNA-i-miR-221 was evaluated by cell proliferation and BrdU uptake assays. In vivo studies were performed with non-obese diabetic/severe combined immunodeficient (NOD.SCID) mice bearing t(4;14) MM xenografts, which were intraperitoneally or intravenously treated with naked LNA-i-miR-221. RNA extracts from retrieved tumors were analyzed for miR-221 levels and modulation of canonical targets expression. H&E staining and immunohistochemistry were performed on retrieved tumors and mouse vital organs., Results: In vitro, LNA-i-miR-221 exerted strong antagonistic activity against miR-221 and induced upregulation of the endogenous target p27Kip1. It had a marked anti-proliferative effect on t(4;14)-translocated MM cells but not on MM cells not carrying the translocation and not overexpressing miR-221. In vivo, systemic treatment with LNA-i-miR-221 triggered significant anti-tumor activity against t(4;14) MM xenografts; it also induced miR-221 downregulation, upregulated p27Kip1 and reduced Ki-67. No behavioral changes or organ-related toxicity were observed in mice as a consequence of treatments., Conclusions: LNA-i-miR-221 is a highly stable, effective agent against t(4;14) MM cells, and is suitable for systemic use. These data provide the rationale for the clinical development of LNA-i-miR-221 for the treatment of MM.

Objective: Large kindreds segregating familial Alzheimer disease (FAD) offer the opportunity of studying clinical variability as observed for presenilin 1 (PSEN1) mutations. Two early-onset FAD (EOFAD) Calabrian families with PSEN1 Met146Leu (ATG/CTG) mutation constitute a unique population descending from a remote common ancestor. Recently, several other EOFAD families with the same mutation have been described worldwide., Methods: We searched for a common founder of the PSEN1 Met146Leu mutation in families with different geographic origins by genealogic and molecular analyses. We also investigated the phenotypic variability at onset in a group of 50 patients (mean age at onset 40.0 +/- 4.8 years) by clinical, neuropsychological, and molecular methodologies., Results: EOFAD Met146Leu families from around the world resulted to be related and constitute a single kindred originating from Southern Italy before the 17th century. Phenotypic variability at onset is broad: 4 different clinical presentations may be recognized, 2 classic for AD (memory deficits and spatial and temporal disorientation), whereas the others are expressions of frontal impairment. The apathetic and dysexecutive subgroups could be related to orbital-medial prefrontal cortex and dorsolateral prefrontal cortex dysfunction., Conclusions: Genealogic and molecular findings provided evidence that the PSEN1 Met146Leu families from around the world analyzed in this study are related and represent a single kindred originating from Southern Italy. The marked phenotypic variability might reflect early involvement by the pathologic process of different cortical areas. Although the clinical phenotype is quite variable, the neuropathologic and biochemical characteristics of the lesions account for neurodegenerative processes unmistakably of Alzheimer nature.

The authors present a case of a rare tumour of the eyelid sebaceous glands with an unfavourable prognosis, and emphasize the importance of carrying out histological examination of all eyelid neoformations to better identify the lesion and obtain an accurate diagnosis. The Authors discuss the histopathologic aspects of this case, and the findings in the literature.

We describe a case of metachronous bilateral interstitial-cell tumor of the testis in a 54-year-old man with no evidence of endocrine symptoms. About 300 Leydig cell tumor cases have been reported in literature and only in 3% the tumor was bilateral. Rare examples have been reported in cryptorchid testis. In adult patients with Leydig cell tumor of the testis, endocrinologic signs occur in 20 per cent of cases and often precede the onset of a palpable testicular mass. Pathological aspects are discussed and a survey of the literature is reported.