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This Special Issue contains the proceedings of the 8th International Symposium on Biological Monitoring in Occupational and Environmental Health (ISBM-8), held in Hanasaari, Espoo, Finland, 6–8 September 2010, under the impeccable organization of the Finnish Institute of Occupational Health (FIOH). The symposium, which takes place usually every three years as an institutional activity of the Scientific Committee on Occupational Toxicology (SCOT) of the International Commission on Occupational Health (ICOH), aims traditionally to present the state-of-the-art research in human biomonitoring for occupational and environmental health. As for the previous event held in 2007 in Beijing, China, ISBM-8 has been organized in collaboration with two other scientific committees of ICOH, the Scientific Committee on Toxicology of Metals (SCTM) and the Scientific Committee on Rural Health (SCRH). The contribution of these two SCs is most appreciated, both in terms of the scientific papers presented and as an opportunity for interaction and future joint activities among the committees, an important part of ICOH policy.

A rather complete mathematical model for a common-rail injection-system dynamics numerical simulation was developed to support experimentation, layout, and control design, as well as performance optimization. The thermofluid dynamics of the hydraulic-system components, including rail, connecting pipes, and injectors was modeled in conjunction with the solenoid-circuit electromagnetics and the mechanics of mobile elements. One-dimensional flow equations in conservation form were used to simulate wave propagation phenomena throughout the high-pressure connecting pipes, including the feeding pipe of the injector nozzle. In order to simulate the temperature variations due to the fuel compressibility, the energy equation was used in addition to mass conservation and momentum balance equations. Besides, the possible cavitation phenomenon effects on the mass flow rate through the injector bleed orifice and the nozzle holes were taken into account. A simple model of the electromagnetic driving circuit was used to predict the temporal distribution of the force acting on the pilot-valve anchor. It was based on the experimental time histories of the current through the solenoid and of the associated voltage that is provided by the electronic control unit to the solenoid. The numerical code was validated through the comparison of the prediction results with experimental data, that is, pressure, injected flow rate, and needle lift time histories, taken on a high performance test bench Moehwald-Bosch MEP2000-CA4000. The novel injection-system mathematical model was applied to the analysis of transient flows through the hydraulic circuit of a commercial multijet second-generation common-rail system, paying specific attention to the wave propagation phenomena, to their dependence on solenoid energizing time and rail pressure, as well as to their effects on system performance. In particular, an insight was also given into the model capability of accurately predicting the wave dynamics effects on the rate and mass of fuel injected when the dwell time between two consecutive injections is varied.

BACKGROUND: The effect of carotid endarterectomy in lowering the risk of stroke ipsilateral to severe atherosclerotic carotid-artery stenosis is offset by complications during or soon after surgery. We compared surgery under general anaesthesia with that under local anaesthesia because prediction and avoidance of perioperative strokes might be easier under local anaesthesia than under general anaesthesia. METHODS: We undertook a parallel group, multicentre, randomised controlled trial of 3526 patients with symptomatic or asymptomatic carotid stenosis from 95 centres in 24 countries. Participants were randomly assigned to surgery under general (n=1753) or local (n=1773) anaesthesia between June, 1999 and October, 2007. The primary outcome was the proportion of patients with stroke (including retinal infarction), myocardial infarction, or death between randomisation and 30 days after surgery. Analysis was by intention to treat. The trial is registered with Current Control Trials number ISRCTN00525237. FINDINGS: A primary outcome occurred in 84 (4.8%) patients assigned to surgery under general anaesthesia and 80 (4.5%) of those assigned to surgery under local anaesthesia; three events per 1000 treated were prevented with local anaesthesia (95% CI -11 to 17; risk ratio [RR] 0.94 [95% CI 0.70 to 1.27]). The two groups did not significantly differ for quality of life, length of hospital stay, or the primary outcome in the prespecified subgroups of age, contralateral carotid occlusion, and baseline surgical risk. INTERPRETATION: We have not shown a definite difference in outcomes between general and local anaesthesia for carotid surgery. The anaesthetist and surgeon, in consultation with the patient, should decide which anaesthetic technique to use on an individual basis. FUNDING: The Health Foundation (UK) and European Society of Vascular Surgery.

Background Idiopathic Pulmonary Fibrosis (IPF) is an aggressive interstitial lung disease with an unpredictable course. Occupational dust exposure may contribute to IPF onset, but its impact on antifibrotic treatment and disease prognosis is still unknown. We evaluated clinical characteristics, respiratory function and prognostic predictors at diagnosis and at 12 month treatment of pirfenidone or nintedanib in IPF patients according to occupational dust exposure. Methods A total of 115 IPF patients were recruited. At diagnosis, we collected demographic, clinical characteristics, occupational history. Pulmonary function tests were performed and two prognostic indices [Gender, Age, Physiology (GAP) and Composite Physiologic Index (CPI)] calculated, both at diagnosis and after the 12 month treatment. The date of long-term oxygen therapy (LTOT) initiation was recorded during the entire follow-up (mean = 37.85, range 12–60 months). Results At baseline, patients exposed to occupational dust [≥ 10 years (n = 62)] showed a lower percentage of graduates (19.3% vs 54.7%; p = 0.04) and a higher percentage of asbestos exposure (46.8% vs 18.9%; p 0.002) than patients not exposed [

Background/Aims: Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the go-to method for obtaining samples from gastrointestinal tract and pancreatic lesions. When the transduodenal approach is utilized, the use of a more flexible needle, such as a nitinol 19-gauge (G) needle, has been recommended. The aim of this study was to evaluate the feasibility and accuracy of 19-G flexible aspiration needles in obtaining samples from solid lesions through a transduodenal approach. Methods: This was a retrospective analysis of prospectively collected data from eight Italian endoscopy centers. Consecutive patients with solid lesions who underwent transduodenal EUS-FNA with a 19-G flexible needle were included. Results: A total of 201 patients were enrolled. According to histology, EUS, radiology and 12 months of follow-up, 151 patients had malignant lesions and 50 patients had benign lesions. EUS-FNA was feasible in all cases. An adequate histologic sample was obtained in all except eight cases (96.1%). The sensitivity of EUS-FNA was 92.1% (95% confidence interval [CI], 86.8%-95.7%), and the specificity was 100% (95% CI, 90.5%-100%). The positive predictive value was 100% (95% CI, 93.4%-100%), and the negative predictive value was 74% (95% CI, 62.8%-82.7%). The diagnostic accuracy was 93.5% (95% CI, 89.2%-96.5%). Conclusions: The transduodenal approach for obtaining samples from solid lesions using a 19-G flexible needle seems feasible and accurate. Clin Endosc 2021;54:229-235

Background Inpatients are at risk for inadequate colon cleansing. Experts recommend 4L-polyethylene-glycol (PEG) solution. A higher colon cleansing adequacy rate for a hyperosmolar 1L-PEG plus ascorbate prep has been recently reported. Aims We aimed to determine whether 1L-PEG outperforms 4L-PEG among inpatients. Methods post-hoc analysis of a large Italian multicenter prospective observational study among inpatients (QIPS study). We performed a propensity score matching between 1L-PEG and 4L-PEG group. The primary outcome was the rate of adequate colon cleansing as assessed by unblinded endoscopists through Boston scale. Secondary outcome was the safety profile. Results Among 1,004 patients undergoing colonoscopy, 724 (72%) were prescribed 4L-PEG and 280 (28%) 1L-PEG. The overall adequate colon cleansing rate was 69.2% (n = 695). We matched 274 pairs of patients with similar distribution of confounders. The rate of patients with adequate colon cleansing was higher in 1L-PEG than in 4L-PEG group (84.3% vs. 77.4%, p = 0.039). No different shift in serum concentration of electrolytes (namely Na+, K+, Ca2+), creatinine and hematocrit were observed for both preparations. Conclusion We found a higher rate of adequate colon cleansing for colonoscopy with the 1L-PEG bowel prep vs. 4L-PEG, with apparent similar safety profile, among inpatients. A confirmatory randomized trial is needed. (ClinicalTrials.gov no: NCT04310332)

Appropriate monitoring and control of modifiable risk factors, such as the level of low-density lipoprotein cholesterol (LDL-C) and other types of dyslipidemia, have an important role in the prevention of cardiovascular diseases (CVD). Recently, various nutraceuticals with lipid-lowering effects have gained attention. In addition to the plant-derived bioactive compounds, recent studies suggested that plant cells are able to release small lipoproteic structures named extracellular vesicles (EVs). The interaction between EVs and mammalian cells could lead to beneficial effects through anti-inflammatory and antioxidant activities. The present study aimed to assess the safety of the new patented plant-based product citraVes™, containing extracellular vesicles (EVs) from Citrus limon (L.) Osbeck juice, and to investigate its ability to modulate different CV risk factors in healthy subjects. A cohort of 20 healthy volunteers was recruited in a prospective open-label study. All participants received the supplement in a spray-dried formulation at a stable dose of 1000 mg/day for 3 months. Anthropometric and hematobiochemical parameters were analyzed at the baseline and after the follow-up period of 1 and 3 months. We observed that the supplement has an effect on two key factors of cardiometabolic risk in healthy subjects. A significant change in waist circumference was found in women after 4 (85.4 [79.9, 91.0] cm, p &lt, 0.005) and 12 (85.0 [80.0, 90.0] cm, p &lt, 0.0005) weeks, when compared to the baseline value (87.6 [81.7, 93.6] cm). No difference was found in men (baseline: 100.3 [95.4, 105.2] cm, 4 weeks: 102.0 [95.7, 108.3] cm, 12 weeks: 100.0 [95.3, 104.7] cm). The level of LDL-C was significantly lower at 12 weeks versus 4 weeks (p = 0.0064). Our study evaluated, for the first time, the effects of a natural product containing plant-derived EVs on modifiable risk factors in healthy volunteers. The results support the use of EV extracts to manage cardiometabolic risk factors successfully.

Background: the lack of standardized pathways for patients with gastrointestinal bleeding may have led to differences in their management and inequity to medical care access. The "Hub & Spoke" model was adopted to fill this gap in many disciplines, but, to our knowledge, no data exist on its efficacy on mortality in GI bleeding. We aimed to evaluate if the "Hub & Spoke" organizational model has an impact on mortality risk from UGIB. Methods: from January 2014 to December 2015, 3324 consecutive patients admitted for UGIB in 50 Italian hospitals were enrolled (1977 patients in hospitals within the "Hub & Spoke" network for digestive hemorrhagic emergency and 1347 in hospitals outside the "Hub & Spoke" network). Clinical, endoscopic and organizational data were recorded. Results: we observed no differences in mortality between patients admitted to hospitals included or not included in the "Hub & Spoke" network (5.2% vs 6.1%, p = 0.3). On multivariate analysis, admission in gastroenterology wards (OR 0.61, p = 0.001) or an academic hospital (OR 0.65, p < 0.056) were independent protective factors while being in "Hub & Spoke" organization system did not affect mortality (OR 1.09, p = 0.57). Conclusion: the "Hub & Spoke" model per sé does not impact on mortality while being treated in academic hospital or gastroenterology wards improved survival.

Background Colonoscopy demands a considerable amount of resources, and little is known about its diagnostic yield among inpatients. Aims To assess indications, diagnostic yield and findings of colonoscopy for inpatients, and to identify risk factors for relevant findings and cancer. Methods Multicentre, prospective, observational study including 12 hospitals. Consecutive adult inpatients undergoing colonoscopy were evaluated from February through November 2019. Results 1,302 inpatients underwent colonoscopy. Diagnostic yield for relevant findings and cancer was 586 (45%) and 112 (8.6%), respectively. Adequate colon cleansing was achieved in 896 (68.8%) patients. Split-dose/same-day regimen was adopted in 847 (65%) patients. Factors associated to relevant findings were age ≥70 years (RR 1.32), male gender (RR 1.11), blood loss (RR 1.22) and adequate cleansing (RR 1.63). Age ≥70 years (RR 2.08), no previous colonoscopy (RR 2.69) and split-dose/same-day regimen (RR 1.59) significantly increased cancer detection. Implementing adequate cleansing and split-dose/same-day regimen in all patients would increase the diagnostic yield for any relevant findings and cancer from 43% to 70% and from 6% to 10%, respectively. Conclusion Relevant colorectal diseases and cancer were frequent among inpatients. Factors associated with detection of relevant findings were identified. Adequate colon cleansing and split-dose/same-day regimen significantly increased colonoscopy diagnostic yield.

Increasing electrification of final uses can be a viable solution towards low-carbon energy systems, when coupled with local renewable power generation. Mountain areas can already benefit from high shares of hydro-power generation, but, at the same time, rely on oil products for transport and for the heating sector in remote areas where natural gas infrastructures are not available. This research work evaluates potential scenarios for the electrification of transport and heating sectors, by coupling the simulation tool EnergyPLAN with a multi-objective optimization algorithm to analyse economic and environmental aspects. Results show that the largest benefits are expected from the electrification of the heating sector. Indeed, a CO2 emissions reduction up to 30% can be reached by acting on the transport sector alone, while up to 65% combining it with measures on heating, industry and agriculture sectors and additional electricity generation from photovoltaic systems. Moreover, the use of heat pumps can lead to significant CO2 emissions decrease with only to a slight increase in the overall annual costs thanks to lower variable costs that partly compensate the higher required initial investment and electricity storage deployment. The optimization analyses also highlight the effect of progressive penetration of electric vehicles in the private cars fleet and hydrogen trucks in the light-duty vehicles one.

Background & Aims Hospitalization is associated with inadequate colon cleansing before colonoscopy. We aimed to identify factors associated to inadequate colon cleansing among inpatients, and to derive and validate a model to identify inpatients with inadequate cleansing. Methods We performed a prospective observational study at 12 hospitals in Italy. Consecutive adult inpatients scheduled for colonoscopy for any indication were enrolled from February through May 2019 (derivation cohort, n = 1016) and from June through August 2019 (validation cohort, n = 508). Inadequate cleansing was defined as Boston bowel preparation scale scores below 2 in any colon segment. We performed multivariate logistic regression to identify factors associated with inadequate cleansing. Results In the combined cohorts, 1032 patients (68%) had adequate colon cleansing. Physicians’ meetings to optimize bowel preparation (odds ratio [OR], 0.42; 95% CI, 0.27–0.65), written and oral instructions to patients (OR, 0.48; 95% CI, 0.36–0.65), admission to gastroenterology unit (OR, 0.71; 95% CI, 0.51–0.98), split-dose regimens (OR, 0.27; 95% CI, 0.20–0.35), a 1-liter polyethylene glycol-based bowel purge (OR, 0.39; 95% CI, 0.23—0.65), and 75% or more intake of bowel preparation (OR, 0.09; 95% CI, 0.05–0.15) significantly reduced odds of inadequate colon cleansing. Alternatively, bedridden status (OR, 2.14; 95% CI, 1.55–2.98), constipation (OR, 2.16; 95% CI, 1.55–3.0), diabetes mellitus (OR, 1.61; 95% CI, 1.18–2.20), use of anti-psychotic drugs (OR, 3.26; 95% CI, 1.62–6.56), and 7 or more days of hospitalization (OR, 1.02; 95% CI, 1.00–1.04) increased risk of inadequate colon cleansing. We developed a model to identify patients with inadequate cleaning using data from patients in the derivation cohort and tested it in the validation cohort. Calibration values were P = .218 for the discrimination cohort and P = .232 for the validation cohort. Discrimination values were c-statistic, 0.78 (95% CI, 0.74–0.81) for the discrimination cohort and c-statistic, 0.73 (95% CI, 0.69–0.78) for the validation cohort. We developed app for use by clinicians. Conclusions In a prospective observational study, we identified setting-, patient- and preparation-related factors that affect colon cleansing among inpatients. We derived and validated a model to identify patients with inadequate preparation and developed an app for clinicians. ClinicalTrials.gov no: NCT03925506

Background and Aims: Most of the evidence supporting endoscopic submucosal dissection (ESD) comes from Asia. European data are primarily reported by specialized referral centers and thus may not be representative of common European ESD practice. The aim of this study is to understand the current state of ESD practice across Italian endoscopy centers. Methods: All Italian endoscopists who were known to perform ESD were invited to complete a structured questionnaire including: operator features and competencies, ESD training details and clinical outcomes over a 2-year period. Results: Twenty-nine operators from 23 centers (69% response rate) completed the questionnaire: 18 (62%) were 150 in 8 (27.5%). Colorectal ESD was predominant for operators with an experience >80 cases. En-bloc resection rates ranged from 77.2 to 97.2% depending on the anatomic location with an R0 resection rate range of 75.3–93.6%. ESD perforation rates in the colon and rectum were significantly lower when experience was >150 compared to 80–150 cases (p < 0.0001 and p = 0.006 for colon and rectum, respectively). Conclusion: ESD in Italy is performed by a significant number of operators. Overall, Italian endoscopists performing ESD have achieved a good competence level. However, there is much variability in training protocols, initial supervision of procedures, practice settings, case mix and procedural volume/year that are likely responsible for some of the suboptimal resectional outcomes and increased perforation risk, mainly in the colon. Standardized training programs, practice parameters and auditing of outcomes are required.

Objective Although split regimen is associated with higher adenoma detection and is recommended for elective colonoscopy, its adoption remains suboptimal. The identification of patient-related barriers may improve its implementation. Our aim was to assess patients' attitude towards split regimen and patient-related factors associated with its uptake. Design In a multicentre, prospective study, outpatients undergoing colonoscopy from 8:00 to 14:00 were given written instructions for 4â €..L polyethylene glycol bowel preparation, offering the choice between split-dose and day-before regimens and emphasising the superiority of split regimen on colonoscopy outcomes. Uptake of split regimen and association with patient-related factors were explored by a 20-item questionnaire. Results Of the 1447 patients (mean age 59.2±13.5â €..years, men 54.3%), 61.7% and 38.3% chose a split-dose and day-before regimens, respectively. A linear correlation was observed between time of colonoscopy appointments and split-dose uptake, from 27.3% in 8:00 patients to 96% in 14:00 patients (p1â €..h (OR 0.55, 95% CI 0.38 to 0.79), low education level (OR 0.72, 95% CI 0.54 to 0.96) and female gender (OR 0.74, 95% CI 0.58 to 0.95) were inversely correlated with the uptake of split-dose. Overall, the risk of travel interruption and faecal incontinence was slightly increased in split regimen patients (3.0% vs 1.4% and 1.5% vs 0.9%, respectively; p=NS). Split regimen was an independent predictor of adequate colon cleansing (OR 3.34, 95% CI 2.40 to 4.63) and polyp detection (OR 1.46, 95% CI 1.11 to 1.92). Conclusion Patient attitude towards split regimen is suboptimal, especially for early morning examinations. Interventions to improve patient compliance (ie, policies to reorganise colonoscopy timetable, educational initiatives for patient and healthcare providers) should be considered. Trial registration number NCT02287051; pre-result.

Background Clinical and psychosocial outcomes of a multimodal surgical approach for chronic intestinal pseudo-obstruction were analyzed in 24 patients who were followed over a 2- to 12-year period in a single center after surgery or intestinal/multivisceral transplant (CTx). Methods The main reasons for surgery were sub-occlusion in surgery and parenteral nutrition–related irreversible complications with chronic intestinal failure in CTx. Results At the end of follow-up (February 2015), 45.5% of CTx patients were alive: after transplantation, improvement in intestinal function was observed including a tendency toward recovery of oral diet (81.8%) with reduced parenteral nutrition support (36.4%) in the face of significant mortality rates and financial costs (mean, 202.000 euros), frequent hospitalization (mean, 8.8/re-admissions/patient), as well as limited effects on pain or physical wellness. Conclusions Through psychological tests, transplant recipients perceived a significant improvement of mental health and emotional state, showing that emotional factors were more affected than were functional/cognitive impairment and social interaction.

Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents. In this study, we engineered HEK293T cells to express the exosomal protein Lamp2b, fused to a fragment of Interleukin 3 (IL3). The IL3 receptor (IL3-R) is overexpressed in CML blasts compared to normal hematopoietic cells and thus is able to act as a receptor target in a cancer drug delivery system. Here we show that IL3L exosomes, loaded with Imatinib or with BCR-ABL siRNA, are able to target CML cells and inhibit in vitro and in vivo cancer cell growth.

Background & aims: Increased morbidity and mortality from liver disease have been reported in chronic hepatitis B surface antigen (HBsAg) carriers, but data on survival are equivocal. To assess the impact of hepatitis B virus (HBV) infection on survival and liver-related complications, we re-evaluated, after a mean follow-up of 30 years, a cohort of 296 blood donors excluded from donation 30 years ago when HBsAg screening became mandatory. Methods: Clinical and ultrasound examination and biochemical and virologic tests were performed. The cause of death was recorded and survival was compared with a control population of 157 HBV-negative blood donors selected at baseline. Results: Thirty-two (10.8%) cases and 14 controls (8.9%) ( P = 0.625) had died; 3 of 32 (9.3%) and 1 of 14 (7.1%) deaths were liver-related. Hepatocellular carcinoma (HCC) caused death in 2 of 296 and 1 of 157 subjects (0.6% in each group). Alcohol-induced cirrhosis occured in the remaining subject. By Cox regression analysis, survival was independently predicted by older age, abnormal γ-glutamyl transpeptidase (GGT) levels, and presence of medical comorbidities at baseline. Unequivocal liver disease was found in 4 carriers only. No disease decompensation occurred during follow-up. Fifty-nine (32.2%) carriers cleared HBsAg (yearly incidence, 1.0%). Full-length serum HBV DNA was present in 32.2% of persistently HBsAg-positive individuals (average titer always 5 copies/mL). Conclusions: Over a 30-year period, chronic HBV carrier blood donors from Northern Italy did not develop clinically significant liver disease, hepatocellular cancer, or other liver-related morbidity or mortality at a higher rate than uninfected controls. The presence of medical comorbidities, older age at diagnosis, and abnormal GGT levels were independent predictors of death among chronic HBV carriers.