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The exact incidence of neurological and cognitive sequelae of COVID-19 in the long term is yet unknown. The aim of this research is to investigate the type of neurological and cognitive impairment in COVID-19 cases of different severity. Two hundred fifteen patients, who had developed COVID-19, were examined 4 months after the diagnosis by means of neurological exam and extensive cognitive evaluation, investigating general cognition, memory, verbal fluency, visuospatial abilities and executive functions. Fifty-two of them were treated in intensive care unit (ICU patients), whereas 163 were not hospitalized (non-ICU patients). Neurological deficits were found in 2/163 (1.2%) of non-ICU and in 7/52 (13.5%) of the ICU cases, all involving the peripheral nervous system. ICU patients performed significantly worse in all the neuropsychological tests and showed a worse age- and education-corrected cognitive impairment: Cognitive Impairment Index (CII) was higher in ICU than in non-ICU patients (median ICU 3 vs 2, p = .001). CII significantly correlated with age in both groups, was unrelated to length of follow- up, diabetes and hypertension and - only for ICU patients- to PaO 2 /FiO 2 at ICU admission. Obtained results support the greater susceptibility of COVID-19 patients, treated in ICU, to develop neurological deficits and cognitive impairment at a four-month follow up, as compared to cases with mild/moderate symptoms., (Copyright © 2021. Published by Elsevier B.V.)

The study aims to investigate the influence of exposure to low concentrations of benzene on urinary biomarkers of nucleic acid oxidative damage and methylation. Benzene exposure was characterized for 93 coke production workers by measuring both airborne benzene and S-phenylmercapturic acid (SPMA) and unmodified benzene (U-B) in urine samples, collected at the end of the shift (ES) and at the next morning before shift (next BS). In the same urinary samples, biomarkers of nucleic acid oxidative damage and methylation were determined. Urinary concentrations of cotinine and creatinine were also determined to evaluate the smoking effect and to normalize urinary concentrations of analytes, respectively. The biomarkers of benzene internal dose, of oxidative damage (8-hydroxyy-7,8-dihydroguanine, 8-hydroxy-7,8-dihydroguanosine and 8-hydroxy-7,8-2'deoxyguanosine) and some of the biomarkers of nucleic acid methylation (5-Methyl-Cytosine, 1-Methyl-Guanine and 7-Methyl-Guanine) were higher in the ES than the next BS samples. Positive associations between ES 5-Methyl-Cytosine and both SPMA and U-B were found. In conclusion, occupational exposure to low levels of benzene seems to be related to urinary ES 5-Methyl-Cytosine that could be a possible biomarker to evaluate the changes of the nucleic acid methylation status., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objectives: We performed a cross-sectional study with the main aim of evaluating occupational exposure to polycyclic aromatic hydrocarbons (PAHs) in workers involved in the pavement construction of a new highway in Northern Italy, where modified bitumen was used as binder for Hot Mix Asphalt., Methods: We applied a combined approach of air and biological monitoring. Both the aerosol and vapour phases of bitumen were collected applying the NIOSH 5506 method. The 16 PAHs listed as high priority by EPA were determined by HPLC-UV. End-of-shift urine samples were collected from 144 workers to determine 1-hydroxypyrene (1-OHP) and 2-naphthol (2-NAP) concentrations after enzyme digestion and HPLC-UV analysis. Socio-demographic and lifestyle information was collected by a questionnaire., Results: Paving workers were actually exposed to PAHs, including carcinogenic compounds, that were measurable only in the aerosol phase. Higher exposure as well as dose levels were measured for the paver group. Biological monitoring confirmed that 1-OHP was less affected by smoking habits as compared to 2-NAP and showed a higher association with occupational exposure., Conclusion: Carcinogenic PAH compounds were detectable only in the aerosol phase and this must be taken into account in the adoption of preventive measures. Biomonitoring supported the superiority of 1-OHP as compared to 2-NAP in assessing the internal dose in such workers., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-copolyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1-97.5%), and span values of particle size distribution (1.03-1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone.

Boron neutron capture therapy (BNCT) is a radiotherapy treatment based on the accumulation in the tumor of a (10)B-containing drug and subsequent irradiation with low energy neutrons, which bring about the decay of (10)B to (7)Li and an α particle, causing the death of the neoplastic cell. The effectiveness of BNCT is limited by the low delivery and accumulation of the used boron-containing compounds. Here we report the development and the characterization of BPO4 nanoparticles (NPs) as a novel possible alternative drug for BNCT. An extensive analysis of BPO4 NP biocompatibility was performed using both mature blood cells (erythrocytes, neutrophils and platelets) and a model of hematopoietic progenitor cells. A time- and concentration-dependent cytotoxicity study was performed on neoplastic coloncarcinoma and osteosarcoma cell lines. BPO4 functionalization with folic acid, introduced to improve the uptake by tumor cells, appeared to effectively limit the unwanted effects of NPs on the analyzed blood components., From the Clinical Editor: Boron neutron capture therapy (BNCT) is a radiotherapy treatment modality based on the accumulation of a (10)B-containing drug and subsequent irradiation with low energy neutrons, inducing the decay of (10)B to (7)Li and an α particle, causing neoplastic cell death. This team of authors reports on a folic acid functionalized BPO4 nanoparticle with improved characteristics compared with conventional BNCT approaches, as demonstrated in tumor cell lines, and hopefully to be followed by translational human studies., (© 2014.)

The aim of this research was to investigate a tough polymer to develop 3D scaffolds and 2D films for tissue engineering applications, in particular to repair urethral strictures or defects. The polymer tested was a graft copolymer of polylactic acid (PLA) synthesized with the rationale to improve the toughness of the related PLA homopolymer. The LMP-3055 graft copolymer (in bulk) demonstrated to have negligible cytotoxicity (bioavailability >85%, MTT test). Moreover, the LMP-3055 sterilized through gamma rays resulted to be cytocompatible and non-toxic, and it has a positive effect on cell biofunctionality, promoting the cell growth. 3D scaffolds and 2D film were prepared using different LMP-3055 polymer concentrations (7.5, 10, 12.5 and 15%, w/v), and the effect of polymer concentration on pore size, porosity and interconnectivity of the 3D scaffolds and 2D film was investigated. 3D scaffolds got better results for fulfilling structural and biofunctional requirements: porosity, pore size and interconnectivity, cell attachment and proliferation. 3D scaffolds obtained with 10 and 12.5% polymer solutions (3D-2 and 3D-3, respectively) were identified as the most suitable construct for the cell attachment and proliferation presenting pore size ranged between 100 and 400μm, high porosity (77-78%) and well interconnected pores. In vitro cell studies demonstrated that all the selected scaffolds were able to support the cell proliferation, the cell attachment and growth resulting to their dependency on the polymer concentration and structural features. The degradation test revealed that the degradation of polymer matrix (ΔMw) and water uptake of 3D scaffolds exceed those of 2D film and raw polymer (used as control reference), while the mass loss of samples (3D scaffold and 2D film) resulted to be controlled, they showed good stability and capacity to maintain the physical integrity during the incubation time., (© 2013.)

Background: Prediction of response to cardiac resynchronization therapy (CRT) is still an unsolved major issue. The interface between left ventricular mechanics, coronary sinus (CS) lead, and pacing delivery has been little investigated., Objective: To investigate CS lead tip movements at baseline and during biventricular pacing (BiV) in the hypothesis that they could provide some insights into left ventricular mechanical behavior in CRT., Methods: Three-dimensional reconstruction of CS lead tip trajectory throughout the cardiac cycle using a novel fluoroscopy-based method was performed in 22 patients with chronic heart failure (19 men; mean age 70 ± 10 years). Three trajectories were computed: before (T-1) and immediately after (T0) BiV start-up and after 6 months (T1). CRT response was the echocardiographic end-systolic volume reduction ≥15% at T1. Metrics describing trajectory at T0, T-1, and T1 were compared between 9 responders (R) and 13 nonresponders (NR)., Results: At T-1 trajectories demonstrated heterogeneous shapes and metrics, but at T0 the variations in the ratio between the two main axes (S1/S2) and in the eccentricity were statistically different between R and NR, pointing out a trajectory's change toward a significantly more circular shape at BiV start-up in R. Remarkably, R and NR could be completely separated by means of the percent variation in S1/S2 from T-1 to T0 (R: 47.5% [31.5% to 54.1%] vs. NR: -25.6% [-67% to -6.5%]). This single marker computed at T0 would have predicted CRT response at T1., Conclusions: Preliminary data showed that CS lead tip trajectory changes induced by BiV were related to mechanical resynchronization., (© 2013 Heart Rhythm Society. All rights reserved.)

Objectives: Aortic valve replacement (AVR) is recommended in patients with symptomatic aortic stenosis (AS). However a large number of elderly patients remain untreated because of a high operative risk. The aim of this study was to assess the risk profile of a group of AS patients, evaluating the prevalence of comorbidities and associated cardiac diseases and their impact on therapeutic decisions., Methods: Two-hundred forty consecutive AS patients underwent complete clinical evaluation, in order to define the stenosis severity, the prevalence of several associated cardiac conditions and comorbidities. Furthermore, the treatment choices based on this approach were recorded., Results: Mean age was 78.6 ± 8.93 years, 75.5% was ≥ 75 years old, 60% females; 226 patients (94.2%) had symptoms and 54.2% was in NYHA classes III-IV. Valve area <1cm(2) was detected in 81.6% of patients. Both comorbidities and associated cardiac diseases were common; particularly, renal dysfunction was detected by estimated glomerular filtration rate in 52.7%, chronic obstructive lung disease in 25.4%, cerebrovascular/peripheral artery disease in 30.8% and 11.6%, respectively, diabetes in 30%, malignancies (current or previous) in 26.6% of patients. Among associated cardiac diseases, coronary artery disease was detected in 43.7%, LV systolic dysfunction in 28.7%, pulmonary hypertension in 67%, at least moderate mitral regurgitation in 32.5% and porcelain aorta in 7.5% of patients. Fourteen asymptomatic patients (pts) (5.9%) remained in follow-up, 77 (32%) underwent surgical AVR, 64 (26.7%) underwent transcatheter valve implantation, 28 (11.6%) underwent balloon valvuloplasty and 57 (23.8%), despite symptoms, remained on medical therapy alone., Conclusions: Comorbidities and coexisting cardiac diseases are very common in AS and may strongly influence the decision-making process., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Some organochlorine compounds, such as polychlorinated biphenyls (PCBs), have a tendency to bioaccumulate in humans and predators at the top of the food chain. We have recently confirmed the transplacental transfer of these compounds and the present study has been designed on the same material with the aim of investigating their potential health effects on newborns from 70 pregnant women, resident in a Northern Italy industrial town. Organochlorine compounds [namely, p,p'-dichlorodiphenyltrichloroethane (p,p'-DDT), p,p'-dichlorodiphenyldichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and PCBs] have been analyzed both in cord and maternal serum, placenta, and maternal subcutaneous adipose tissue by GC-MSD. p,p'-DDT levels in the adipose tissue resulted significantly (p<0.05) related to birth length. Mothers of neonates born by preterm programmed caesarean delivery showed significantly (p<0.005 for both) higher serum p,p'-DDE serum concentrations and p,p'-DDT levels in the adipose tissue, as compared to mothers delivering at term., (Copyright © 2011 Elsevier B.V. All rights reserved.)

AgI-doped silver oxide glasses are of interest both for their possible applications in electrochemical devices, and as a model system to study the transport/structure relationships in ionic glasses. Here we summarize the information given by 1-D and 2-D solid-state NMR measurements on both the cations dynamics and short (and medium) range structure of several glassy systems. Emphasis is given to understand how AgI enters into the glass matrix. A new and careful analysis of our previously reported 109Ag 1-D data shows that the glass matrix plays a relevant role in determining the efficiency of carriers formation, as well as their mobility. Finally, as an example of a modern 2-D NMR application to these materials, we report the first 11B and 17O Multiple Quantum MAS study on a glass of the system AgI:Ag2O:2B2O2, which confirms the nearly complete absence of non-bridging oxygens (NBOs) in the silver diborate composition.

Background: A prolonged treatment with oral anticoagulants has been claimed to reduce the incidence of newly diagnosed cancer in the long-term follow-up of patients with venous thromboembolism., Objectives: In a multicenter prospective study we assessed the incidence of newly diagnosed clinically overt cancer in patients with a first episode of idiopathic venous thromboembolism (VTE) treated with oral anticoagulants for 3 months or 1 year., Patients and Methods: Consecutive patients with an idiopathic venous thromboembolism who had completed 3 months of oral anticoagulant therapy without having a recurrence, bleeding or newly diagnosed cancer were randomized to discontinue oral anticoagulant therapy or to continue it for nine additional months. Idiopathic venous thromboembolism was defined as thrombosis occurring in the absence of known cancer, known thrombophilia, or temporary risk factors for venous thromboembolism. All patients were followed up for at least 1 year after randomization., Results: A total of 429 patients, 265 patients with DVT and 164 with PE, were followed up for an average of 43.7 months after randomization. A newly diagnosed cancer occurred in 32 patients (7.5%), 13 (6.2%) of the 210 patients treated for 3 months and 19 (8.7%) of the 219 patients treated for 1 year (RR = 0.71, 95% confidence interval 0.36-1.41)., Conclusions: The incidence of newly diagnosed clinically overt cancer is not reduced in patients with idiopathic venous thromboembolism treated with 1-year anticoagulant treatment compared with patients treated for 3 months.

The effect of cycloheximide (CH) on the fasting-induced changes of rat liver cell and protein turnover has been investigated. Late starvation phase (3-4-day-fasting period) was characterised by a decrease in liver weight and protein and DNA content. The loss of DNA was not related to liver cell necrosis but due not only to depression of cell proliferation as shown by the drop in the labelling index but also induction of apoptosis. This type of apoptosis was documented by the increase in the apoptotic index (cells labelled by TUNEL) and transglutaminase activity as well as by DNA fragmentation. The liver cells of fasted rats appeared smaller as shown by the higher cell density and DNA/protein ratio than in controls. Females were more resistant to fasting-induced apoptosis than males. A single dose of CH, a drug primary known as inhibitor of protein synthesis, induced or enhanced apoptosis in fed and 2-days fasted male rats, respectively, without any sign of cell necrosis. On the contrary, the administration of repeated doses of CH blocked apoptosis induced by fasting. CH "froze" protein and DNA content as well as apoptotic process at the level of 2 days-fasted rats. While fasting-induced liver protein loss resulted from a marked reduction in protein synthesis with a slight decrease in degradation, repeated treatment with CH virtually blocked protein loss by abolishing protein catabolism. These data suggest a direct relationship between the catabolic side of protein turnover and the apoptotic process.