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Introduction During the COVID-19 pandemic, health workers represented a group particularly vulnerable to work-related stress, but prevention and management of psychiatric symptoms are still under evaluation. Neurofeedback is a safe and non-invasive neuromodulation technique with the target of training participants in the self-regulation of neural substrates underlying specific psychiatric disorders. Protocols based on the increase of alpha frequencies, associated with the process of relaxation, are used for the treatment of stress, anxiety and sleep disturbances.ObjectivesThe aim of the present study was to assess the effectiveness of an alpha-increase NF protocol for the treatment of stress in healthcare workers exposed to the COVID-19 pandemic.MethodsEighteen medical doctors belonging to the Sacco Hospital were recruited during the COVID-19 health emergency and underwent a 10 sessions NF alpha-increase protocol during two consecutive weeks. The level of stress was assessed at the beginning (T0) and at the end (T1) of the protocol through the following questionnaires: Severity of Acute Symptoms Stress (SASS), Copenhagen Burnout Inventory (CBI), Pittsburgh Sleep Quality Index (PSQI), Brief-COPE. Statistical analyses were performed with Paired Samples t-Test for continuous variables, setting significance at p < 0.05.ResultsA significant increase in alpha waves mean values between T0 and T1 was observed. In addition, a significant reduction in the PSQI test score between T0 and T1 was observed.ConclusionsAlpha-increase protocol showed promising results in terms of stress modulation, sleep quality improvement and safety profile in a pilot sample of health-care workers. Larger controlled studies are warranted to confirm present results.

IntroductionSeveral evidence recognizes Brain Derived Neurotrophic Factor (BDNF) as a promising biomarker in the pathophysiology of psychiatric disorders, including Obsessive-Compulsive Disorder (OCD), considering the involvement of epigenetic regulation in BDNF altered expression.ObjectivesThis study aims to investigate, in a sample of OCD patients, the epigenetic modulation in terms of levels of methylation and hydroxymethylation on the BDNF gene exon I promoter.MethodsFifty OCD patients, recruited from Psychiatry Unit 2, Sacco University Hospital in Milan and fifty healthy controls, comparable by age and gender. Saliva samples were collected by oral swab and epigenetic analysis were performed at the University of Teramo. Statistical analyses were performed with t test with Bonferroni correction.ResultsData analysis showed a significant decrease in 5-methyl cytosine levels (5mC) (mean OCD: 1.221%; mean CTRL: 1.784%; p < 0.001) and a significant increase in 5-Hydroxy-methyl cytosine levels (5hmC) (mean OCD: 1.018%; mean CTRL: 0.527% p< 0.0001) in BDNF gene exon I promoter of OCD patients compared to controls. Regarding 5mC of site 3 and 5hmC of site 1 and 2 of the exon I promoter CpG islands, no statistical significance was found.ConclusionsPresent results showed significant differences in epigenetic modulation of BDNF gene, which might not be univocally interpreted. They could represent an intrinsic OCD characteristic or the effect of antidepressant drugs, assumed by all recruited patients. Further studies, comparing OCD subjects in treatment vs drug-free, are necessary to define BDNF epigenetic modulation role and its possible use as biomarker in the characterization of OCD.DisclosureNo significant relationships.

Background and aim: The objective of this cross-sectional study was to evaluate the degree of glycaemic control and the frequency of diabetic complications in Italian people with diabetes who were treated with continuous subcutaneous insulin infusion (CSII). Methods and results: Questionnaires investigating the organisation of diabetes care centres, individuals’ clinical and metabolic features and pump technology and its management were sent to adult and paediatric diabetes centres that use CSII for treatment in Italy. Information on standard clinical variables, demographic data and acute and chronic diabetic complications was derived from local clinical management systems. The sample consisted of 6623 people with diabetes, which was obtained from 93 centres. Of them, 98.8% had type 1 diabetes mellitus, 57.2% were female, 64% used a conventional insulin pump and 36% used a sensor-augmented insulin pump. The median glycated haemoglobin (HbA1c) level was 60 mmol/mol (7.6%). The HbA1c target (i.e. 18 years) was achieved in 43.4% of paediatric and 23% of adult participants. Factors such as advanced pump functions, higher rate of sensor use, pregnancy in the year before the study and longer duration of diabetes were associated with lower HbA1c levels. The most common chronic complications occurring in diabetes were retinopathy, microalbuminuria and hypertension. In the year before the study, 5% of participants reported ≥1 episode of severe hypoglycaemic (SH) episodes (SH) and 2.6% reported ≥1 episode of ketoacidosis. Conclusions: Advanced personal skills and use of sensor-based pump are associated with better metabolic control outcomes in Italian people with diabetes who were treated with CSII. The reduction in SH episodes confirms the positive effect of CSII on hypoglycaemia. Clinical trial registration number: NCT 02620917 (ClinicalTrials.gov).

Patient sex is known to influence the response to general and regional anaesthesia and recovery after surgery. However, most studies come from analyses carried out on middle-aged patients. As most of the patients admitted to the post-anaesthesia recovery room in our institution are elderly, we took the opportunity to investigate the association between sex and incidence of early adverse events in this older population of patients after major surgery. Consecutive patients undergoing general, orthopaedic, urological and gynaecological surgery, admitted to the recovery room of our institution over a 15-month period, were retrospectively studied. The following adverse events were considered in the analysis: shivering, postoperative nausea and vomiting, hypotension and hypertensive responses, new arrhythmias requiring treatment, acute respiratory failure and desaturation. A total of 1347 patients (mean age 73.3±15.1 years, 61.4% women) were included. Women showed a higher incidence of shivering (relative difference +48%, P=0.0003), postoperative nausea and vomiting (+91%, P0.0001), hypotension (+32%, P=0.044) and desaturation (+60%, P=0.0030) than men. The incidence of hypertensive response, arrhythmias and acute respiratory failure were not statistically significantly different. The findings of this exploratory study suggest that women have a higher risk of early postoperative adverse events even in a more elderly population.

Background: Maintenance steroid therapy is associated with significant morbidity and mortality in renal transplant recipients. Elimination of the many long-term side effects of corticosteroids, including those that impinge on cardiovascular risk, remains a laudable goal in designing immunosuppressive protocols. However, concern persists that prednisone-free maintenance immunotherapy in kidney transplant recipients will result in an increase incidence of acute rejections, renal dysfunction and ultimate graft loss. Methods: From 24 March 2003 to 1 December 2004, 84 kidney transplant recipients (61 deceased donor, 23 living donors) discontinued prednisone on post-operative day 6. Immunotherapy consisted of polyclonal antibody induction (thymoglobulin) for five d and prednisone intraoperatively with a rapid taper over the next six d. Maintenance therapy consisted of a sirolimus and CellCept-based calcineurin inhibitor-minimization protocol. Tacrolimus and mycophenolate mofetil (CellCept) were initiated on day 0. Sirolimus immunotherpay was started on post-operative day 6 concomitant with the cessation of steroids. We compared outcomes with that of our historical controls, treated with sirolimus and tacrolimus, who did not discontinue steroids. In addition, we analyzed outcomes independently for recipients of living and deceased donors in the steroid-free protocol. Results: The recipients on prednisone-free maintenance immunosuppression had excellent 2.5-yr actuarial patient survival (97%), graft survival (93%), and acceptable acute rejection-free graft survival (89%). The mean serum creatinine level (±SD) at one yr was 1.5 ± 0.6 mg/dL and at two yr was 1.5 ± 0.6 mg/dL. We noted that 5% of recipients developed cytomegalovirus (CMV) syndrome; 1%, polyoma nephropathy; 1%, post-transplant lymphoproliferative disorder (PTLD), and 5% developed post-transplant diabetes mellitus (PTDM). In all, 91% of kidney recipients with functioning grafts remain steroid-free as of 31 December 2005. When compared with historical controls, the recipients on the early steroid-withdrawal (ESW) protocol had comparable graft survival, acute rejection-free survival, graft function, but significantly better patient actuarial survival (p = 0.048). In addition, recipients on the steroid-free protocol had decreased prevalence of four risk factors for cardiovascular disease when compared with historical controls: hypertension (p = 0.008), hyperlipidemia (p = 0.003), weight gain (p = 0.024), and incidence of PTDM (p = 0.015). Conclusion: Early steroid-withdrawal in renal transplant recipients with a sirolimus and CellCept-based calcineurin inhibitor-minimimization protocol can effectively reduce many of the steroid-related side effects, decrease risk factors for cardiovascular disease, and is associated with improved recipient survival without compromising graft function.

In the past, epidemiological studies indicated a possible correlation between the exposure to ELF fields and cancer. Public concern over possible hazards associated with exposure to extremely low frequency magnetic fields (ELFMFs) stimulated an increased scientific research effort. More recent research and laboratory studies, however, have not been able to definitively confirm the correlation suggested by epidemiological studies. The aim of this study was to evaluate the effects of 50 Hz magnetic fields in human blood cells exposed in vitro, using several methodological approaches for the detection of genotoxicity. Whole blood samples obtained from five donors were exposed for 2 h to 50 Hz, 1 mT uniform magnetic field generated by a Helmholtz coil system. Comet assay, sister chromatid exchanges (SCE), chromosome aberrations (CA), and micronucleus (MN) tests were used to assess DNA damage, one hallmark of malignant cell transformation. The effects of a combined exposure with X-rays were also evaluated. Results obtained do not show any significant difference between ELFMFs exposed and unexposed samples. Moreover, no synergistic effect with ionizing radiation has been observed. A slight but significant decrease of cell proliferation was evident in ELFMFs treated samples and samples subjected to the combined exposure. Bioelectromagnetics 25:41–48, 2004. © 2003 Wiley-Liss, Inc.

To evaluate whether the application of heparin treated circuits for elective coronary artery surgery improves postoperative recovery, a European multicenter randomised clinical trial was carried out.In 11 European heart centers, 805 low-risk patients underwent cardiopulmonary bypass (CPB) with either an untreated circuit (n = 407) or an identical but heparin treated circuit (n = 398, Duraflo II).Significant differences were found among participating centers with respect to patient characteristics, blood handling procedures and postoperative care. The use of heparin treated circuits revealed no overall changes in blood loss, blood use, time on ventilator, occurrence of adverse events, morbidity, mortality, and intensive care stay. These results did not change after adjustment for centers and (other) prognostic factors as analysed with logistic regression. In both groups no clinical or technical (patient or device related) side effects were reported. Because female gender and aortic cross clamp time appeared as prognostic factors in the logistic regression analysis, a subgroup analysis with these variables was performed. In a subpopulation of females (n = 99), those receiving heparin treated circuits needed less blood products, had a lower incidence of rhythm disturbances and were extubated earlier than controls. In another subgroup of patients with aortic cross clamp time exceeding 60 min (n = 197), the amount of patients requiring prolonged intensive care treatment (24 h) was significantly lower when they received heparin treated circuits versus controls.These findings suggest that improved recovery can be expected with heparin treated circuits in specific higher risk patient populations (e.g. females) and when prolonged aortic cross clamp time is anticipated. Further investigations are recommended to analyses the clinical benefit of heparin treated circuits in studies with patients in different well defined risk categories and under better standardised circumstances.

To investigate the relationship between lymphocyte decrease and cytogenetic response in individual patients undergoing radiotherapy.Peripheral blood lymphocytes obtained from 35 patients with pelvic and from 14 with head and neck tumours before and during radiotherapy were PHA-stimulated in vitro and the cultures prepared for the cytokinesis-block micronucleus test. For some patients only, the micronucleus test was carried out after 2 Gy in vitro X-irradiation, and 3-aminobenzamide (2 mM) was used to calculate the 3AB-index.The initially observed individual variation in the decrease of lymphocytes disappeared with increasing number of radiation exposures, reaching a stable level at about 500/microl lymphocytes in the blood. The slope of the relationship between the reciprocal of the lymphocyte decrease ratio and equivalent dose indicates the radiosensitivity of the lymphocyte pool in individual patients. The micronucleus test performed on lymphocytes obtained from patients during radiotherapy (in vivo) provided a lower cytogenetic response than the in vitro micronucleus yield for the same dose, so it was possible to calculate the cytogenetic recovery factor k. A correlation was found between the 3AB-index calculated before radiotherapy, and the recovery factor k.The 3AB-index, the micronucleus frequency after 2 Gy in vitro X-irradiation, and the cytogenetic recovery factor are proposed as predictive of individual response to radiotherapy.

Brugada Syndrome (BS) is a polygenic inherited cardiac disease characterized by life-threatening arrhythmias and high incidence of sudden death. In this study, two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (LC-MS/MS) was used to investigate specific changes in the plasma proteome of BS patients and family members sharing the same gene mutation (SCN5AQ1118X), with the aim to identify novel disease biomarkers. Our data demonstrate that the levels of several proteins were significantly altered in BS patients compared with controls. In particular, apolipoprotein E, prothrombin, vitronectin, complement-factor H, vitamin-D-binding protein, voltage-dependent anion-selective channel protein 3 and clusterin were considerably increased in plasma sample of BS patients, whereas alpha-1-antitrypsin, fibrinogen and angiotensinogen were considerably decreased; moreover, post-translational modifications of antithrombin-III were detected in all affected individuals. On the light of these results, we hypothesize that these proteins might be considered as potential markers for the identification of disease status in BS.

Recently improved understanding of the pathogenesis of human head and neck squamous cell carcinoma (HNSCC) has led to the development of new, molecular-based therapeutic strategies, one of the more promising is the utilisation of tyrosine kinase (TK) inhibitors, targeting epidermal growth factor receptor (EGFR). In this study, we tested for gefitinib effectiveness in a broad panel of 12 newly established HNSCC cell lines, investigating its ability to reduce cell growth, to induce apoptosis and to modulate cell cycle and various EGFR pathway-related targets. Gefitinib IC50 values ranged between 0.064 and 33 microM, its capability to induce apoptosis and cell accumulation in G0/G1 phase was cell line-specific, and the main EGFR-related pathway involved in gefitinib activity was PI3K/Akt/mTor. We characterised our in vitro panel extensively, with the aim to identify predictive factors for gefitinib effectiveness; all cell lines were free of human papillomavirus infection, two were positive for Fhit expression, four expressed wild-type p53, and all of them variously expressed the other two p53 family members, p63 and p73. The comparison between the targets analysed and gefitinib effectiveness evidenced the absence of a clear relationship, excluding them as predictive factors for gefitinib efficacy. Our results confirmed the in vitro efficacy of an anti-EGFR approach, but other targets than those analysed here should be characterised in order to identify valid predictive factors for gefitinib utilisation.

We have applied the cytokinesis-block micronucleus assay to peripheral blood lymphocytes of patients undergoing radiotherapy in pelvic and pulmonary sites, in order to evaluate the individual cytogenetic response. Our cytogenetic data correlated with the equivalent whole-body dose are homogeneous and compare well with the data presented by other authors. We have used an exponential mathematical formula to calculate the attenuation of the cytogenetic effect with time. The k coefficient (cytogenetic recovery factor) in the formula expresses the degree of attenuation. In lymphocytes from patients after radiotherapy, the trend of the micronucleus frequency observed after 2 Gy of in vitro X-irradiation demonstrates that the cytogenetic effect obtained in vitro is added to that obtained in vivo. The k coefficient is inversely proportional to the micronucleus frequency observed after 2 Gy in vitro. The micronucleus assay and the cytogenetic recovery factor are proposed as suitable diagnostic tools for application in the field of radiotherapy.