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Objectives: Since 1991 hepatitis B vaccination has been mandatory for all newborns in Italy. The aim of the study was to verify the long-term seroprevalence and the efficacy of hepatitis B vaccination in medical students of the University of Siena.Material and Methods: A cross-sectional observational study was conducted on a population of 850 medical students of the University of Siena (322 males and 528 females, mean age: 23 years) by obtaining from the medical reports the serological analysis data for the total anti-hepatitis B antibodies (HBsAb) and information on hepatitis B vaccination (number of vaccine doses, age at the first vaccination, time since the final vaccination dose, country of origin). Raw odds ratios (ORs) and 95% confidence intervals (CIs) were initially calculated to evaluate the association between 2 variables. The adjusted ORs were then calculated using a multivariate logistic regression model to study the association between the variables and the possible confounding factors.Results: Overall, 593 students (69.76%) were immunized against hepatitis B, while 257 (30.24%) had HBsAb antibody titer <10 mIU/ml. From the OR calculation, an inverse correlation emerged between seropositivity to hepatitis B and age, and between seropositivity to hepatitis B and the age at the first vaccination dose. There was also a correlation between seropositivity and the number of vaccination doses received. By performing the multivariate logistic analysis, correlations with these variables were confirmed.Conclusions: A significant part of the studied population was not immunized against hepatitis B virus, despite the fact that vaccination had been carried out as prescribed by law. The results of the study reaffirm the importance of health surveillance in subjects at biological risk such as medical students. Int J Occup Med Environ Health. 2022;35(1):75-80. [ABSTRACT FROM AUTHOR]

Chorea-Acanthocytosis (ChAc) is a devastating, little understood, and currently untreatable neurodegenerative disease caused by VPS13A mutations. Based on our recent demonstration that accumulation of activated Lyn tyrosine kinase is a key pathophysiological event in human ChAc cells, we took advantage of Vps13a−/− mice, which phenocopied human ChAc. Using proteomic approach, we found accumulation of active Lyn, γ-synuclein and phospho-tau proteins in Vps13a−/− basal ganglia secondary to impaired autophagy leading to neuroinflammation. Mice double knockout Vps13a−/− Lyn−/− showed normalization of red cell morphology and improvement of autophagy in basal ganglia. We then in vivo tested pharmacologic inhibitors of Lyn: dasatinib and nilotinib. Dasatinib failed to cross the mouse brain blood barrier (BBB), but the more specific Lyn kinase inhibitor nilotinib, crosses the BBB. Nilotinib ameliorates both Vps13a−/− hematological and neurological phenotypes, improving autophagy and preventing neuroinflammation. Our data support the proposal to repurpose nilotinib as new therapeutic option for ChAc patients. [ABSTRACT FROM AUTHOR]

Summary: Selectins play a central role in leukocyte trafficking by mediating tethering and rolling on vascular surfaces. Here we have reported that T cell immunoglobulin and mucin domain 1 (TIM-1) is a P-selectin ligand. We have shown that human and murine TIM-1 binds to P-selectin, and that TIM-1 mediates tethering and rolling of T helper 1 (Th1) and Th17, but not Th2 and regulatory T cells on P-selectin. Th1 and Th17 cells lacking the TIM-1 mucin domain showed reduced rolling in thrombin-activated mesenteric venules and inflamed brain microcirculation. Inhibition of TIM-1 had no effect on naive T cell homing, but it reduced T cell recruitment in a skin hypersensitivity model and blocked experimental autoimmune encephalomyelitis. Uniquely, the TIM-1 immunoglobulin variable domain was also required for P-selectin binding. Our data demonstrate that TIM-1 is a major P-selectin ligand with a specialized role in T cell trafficking during inflammatory responses and the induction of autoimmune disease. [Copyright &y& Elsevier]

Patients with aggressive non- Hodgkin lymphoma ( NHL) who relapse after autologous stem cell transplantation ( ASCT) have a poor prognosis. Additional therapy is often poorly tolerated, and new treatment modalities are needed. This efficacy and safety study was a retrospective analysis of two phase II trials ( NHL-002 and NHL-003) that studied single-agent lenalidomide in patients with relapsed/refractory aggressive NHL with prior ( n = 87) compared with no prior ASCT ( n = 179). The overall response rate in the ASCT group was 39% [14% complete response ( CR)], including 29% in patients with diffuse large B-cell lymphoma, 63% in mantle cell lymphoma, and 60% in transformed lymphoma. The timing of transplant relative to receiving lenalidomide had no effect on outcomes. Median progression-free survival for the ASCT group was 3·7 months (16·9 months for patients in CR; 7·3 months for partial responders) at a median 12·5-month follow-up. Median response duration was 7·9 months. Regardless of prior ASCT, lenalidomide monotherapy was efficacious in heavily pretreated patients with aggressive, relapsed/refractory NHL, with a safety profile that was consistent with prior studies of single-agent lenalidomide. [ABSTRACT FROM AUTHOR]

Summary Transformed lymphoma (TL) represents a heterogeneous group of lymphomas with an aggressive course and poor prognosis. We assessed the clinical benefit of single-agent lenalidomide based on histological origin, including transformed follicular lymphoma (tFL) and transformed chronic lymphocytic leukaemia/small lymphocytic lymphoma (tCLL/SLL). Our analysis included 33 patients with TL. Patients received lenalidomide at a median dose of 25 mg/d. The overall response rate (ORR) was 46%, with a median response duration of 12·8 months after a median follow-up of 5·6 months. Median progression-free survival was 5·4 months. Among patients with tFL, ORR was 57%, with a median response duration of 12·8 months. None of the patients with tCLL/SLL responded to lenalidomide monotherapy. The most common grade 3/4 adverse events were reversible myelosuppression. Our results suggest that the original lymphoma histology (i.e. FL) in TL patients may potentially be associated with response to salvage lenalidomide monotherapy. [ABSTRACT FROM AUTHOR]

Background: Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL).Methods: Patients received oral lenalidomide 25 mg on days 1–21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR).Results: Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months [95% confidence interval (CI) 2.7–5.1]. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0–NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively.Conclusion: Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin’s lymphoma. [ABSTRACT FROM AUTHOR]

Abstract: It is well known that the cannabinoid system has a significant role in the regulation of the immune responses. Cannabinoid receptors CB1 and CB2 are expressed on T lymphocytes and mediate the immunomodulatory effects of cannabinoids on T cell functions. Here we show that the treatment of proteolipid protein (PLP)139–151-specific T cells with SR141716A, a CB1 inverse agonist and prototype of the diarylpyrazoles series, induced a strong inhibition of firm adhesion in inflamed brain venules in intravital microscopy experiments. In contrast, SR144528, a potent CB2 inverse agonist, had no significant effect on both rolling and arrest of activated T cells. In addition, two analogs of SR141716A and CB1 inverse agonists, AM251 and AM281 inhibited encephalitogenic T cell adhesion suggesting that selective CB1 inverse agonism interfere with lymphocyte trafficking in the CNS. Flow cytometry experiments showed that CB1 inverse agonists have no effect on adhesion molecule expression suggesting that CB1 blockade interferes with signal transduction pathways controlling T cell adhesion in inflamed brain venules. In addition, integrin clustering was not altered after treatment with CB1 inverse agonists suggesting that adhesion blockade is not due to the modulation of integrin valency. Notably, the inhibitory effect exerted by AM251 and AM281 on the adhesive interactions was completely reverted in the presence of protein kinase A (PKA) inhibitor H89, suggesting that cAMP and PKA activation play a key role in the adhesion blockade mediated by CB1 inverse agonists. To further strengthen these results and unveil a previously unknown inhibitory role of cAMP on activated T cell adhesion in vivo in the context of CNS inflammation, we showed that intracellular increase of cAMP induced by treatment with Bt2cAMP, a permeable analog of cAMP, and phosphodiesterase (PDE) inhibitor theophylline efficiently blocked the arrest of encephalitogenic T cells in inflamed brain venules. Our data show that modulation of CB1 function has anti-inflammatory effects and suggests that inverse agonism of CB1 block signal transduction mechanisms controlling encephalitogenic T cells adhesion in inflamed brain venules by a PKA-dependent mechanism. [Copyright &y& Elsevier]

Lenalidomide gained Food and Drug Administration (FDA) approval for treatment of patients with relapsed or refractory multiple myeloma (MM) in combination with dexamethasone in June 2006. In April 2005, the FDA and patient advocacy groups requested an expanded access programme to both provide lenalidomide to patients likely to benefit and obtain additional safety information. Relapsed/refractory MM patients received lenalidomide 25 mg/d (days 1–21) and dexamethasone 40 mg/d (days 1–4, 9–12, and 17–20 of cycles 1–4; days 1–4 only from cycle 5 onwards), in 4-week cycles until disease progression, study drug discontinuation, or lenalidomide approval. Of the 1438 patients enrolled, ∼60% were male, median age was 64 years, and 61·7% had Durie-Salmon stage III disease. Median time on study was 15·4 weeks (range: 0·1–49·1) and median dose was 25 mg. The most common adverse events (AEs) were haematological (49%), gastrointestinal (59%), and fatigue (55%). The most common grade ≥3 AEs were haematological (45%), fatigue (10%), and pneumonia (7%). The most common serious AEs were pneumonia (8%), pyrexia (4%), and deep-vein thrombosis (3%). Primary cause of death was disease progression (10%). Safety data confirmed known AEs of lenalidomide plus dexamethasone therapy in patients with relapsed/refractory MM. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma with a poor prognosis following first relapse. We present a subgroup analysis of an open-label phase II trial investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL. Oral lenalidomide 25 mg was self-administered once daily on days 1–21 every 28 d for up to 52 weeks, according to tolerability or until disease progression. The primary endpoint was overall response rate (ORR) and secondary endpoints were duration of response, progression-free survival (PFS) and safety. Among 15 patients with MCL with a median disease duration of 5·1 years and a median of four prior treatments, the ORR was 53%. Three patients (20%) had a complete response and 5 (33%) had a partial response. The median duration of response was 13·7 months and median PFS was 5·6 months. Four of five patients who relapsed after transplantation and two of five patients who previously received bortezomib responded to lenalidomide. The most common grade 4 adverse event was thrombocytopenia (13%) and the most common grade 3 adverse events were neutropenia (40%), leucopenia (27%) and thrombocytopenia (20%). In conclusion, oral lenalidomide monotherapy is well tolerated and active in relapsed or refractory MCL. [ABSTRACT FROM AUTHOR]

Background and aim Falls and fall-related injuries are a major public health issue which needs global attention due to its clinical and socioeconomic impact. Important risk factors for falls are polypharmacy and the assumption of so-called Fall Risk Increasing Drugs (FRIDs). Aims of our study were to investigate the associations between falls and the use of medications among inpatients by conducting a retrospective case-control study in a rehabilitation hospital in Northern Italy in 2018. Methods A Conditional Logistic Regression was performed to analyze the impact that 13 types of FRIDs individually and the number of administrated FRIDs had on the risk of falling. A second regression model was obtained adjusting the case-control matching for CIRS, Morse and Barthel scores. Results We identified 148 cases and 444 controls. 3 types of FRIDs were significantly correlated (p < 0,05) with an increased risk of falling: Antipsychotics, Antidepressants, Diuretics. Antidepressants were the only type of FRID significantly correlated (p=0,008) even in the model adjusted for CIRS, Morse and Barthel scores. The unadjusted model showed that the addition of one type of FRID to therapy was significantly associated with the fall event (p<0.05). Conclusion Assumption of drugs, in particular antidepressant and polypharmacy, can play a role in hospital falling. The fall risk assessment tools available, suffer from low specificity and sensitivity and do not assess these risk factors. A holistic approach with a multidimensional evaluation of the patient through screening tools, functional assessment tools and a full medical evaluation should be pursued to improve prediction.

Introduction: Online grooming is an active communicative entrapment network involving a wide range of techniques. The interactions that groomers have with minors online are complex. The purpose of the present literature review was to contribute to the existing knowledge base regarding online sex offender typologies, predatory tactics and techniques., Evidence Acquisition: We conducted a review of the current literature by an initial database research of papers published since 1990. Three independent reviewers selected relevant articles, initially based on title and abstract analysis, then by full text in order to make a final determination. After the final selection, a total of 21 articles were reviewed., Evidence Synthesis: Overall, abundant data describing both groomer characteristics and grooming strategies are available in the literature, with authors attempting to analyze and adapt these to ever-complex models. However, the various models often feel redundant, determining a certain difficulty in understanding which would be the most suitable model to apply, making comparing data from different studies oftentimes troublesome., Conclusions: In our opinion, it would be desirable to reach a consensus on fewer univocally-interpretable models that would be easier to adopt as preventive tools against online grooming, in combination with other strategies. The present study may provide parents and guardians with information useful for keeping their youth safer while online, as well as data that may assist in the development of policy recommendations and prevention strategies, overall aiming to reduce the phenomenon of online grooming.

Introduction: Since its diffusion in the 1990s, the Internet has developed into a fully integrated component of the lives of teenagers across the globe. As use of the Internet by underage youth has evolved and increased over the past decades, concerns about how technology may contribute to minors becoming victims of online sex crimes, including online grooming, have heightened. The present literature review contributes to the existing knowledge base regarding the epidemiology of the online grooming process, exploring key themes and issues arising in this area., Evidence Acquisition: We conducted a review of the current literature by an initial database research of papers published since 1990. Three independent reviewers selected relevant articles, initially based on title and abstract analysis, then by full text in order to make a final determination. After the final selection, a total of 37 articles were reviewed., Evidence Synthesis: The articles reviewed report highly heterogenous results with regards to epidemiological data, estimating a prevalence of the online grooming phenomenon between 9% and 19%. Factors influencing minors' risk of online grooming included increasing age, gender, sexual minority orientation, diagnosis of mental disease, conflictual relationships with parents and risk-taking behaviors (e.g. chat room and social networking site use)., Conclusions: Although the true prevalence of online grooming is not available, it is a significant issue among minors. Thus, it is important to educate youth on responsible internet use, starting at the earliest age and continuing during adolescence.

This study aimed at assessing the validity of self-collected (self-sampled) oropharyngeal (OP) swabs among healthcare workers compared to those collected by trained sentinel general practitioners (GP-sampled) from individuals with influenza-like illness (ILI), to be implemented in epidemiological studies and/or surveillance programs of viral pathogens involved in community respiratory infections. In our study, OP swabs were collected from adults (>18 years) with ILI during the 2018-2019 influenza season. Two groups of samples were considered: group 1-131 self-sampled OP swabs collected by healthcare workers after being trained on the sampling procedure; group 2-131 GP-sampled OP swabs collected from outpatients by sentinel GPs operating within the Italian Influenza Surveillance Network. To assess swabbing quality, following RNA extraction, each sample was tested for the presence of the human ribonuclease P gene (RNP) by in-house real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Samples with a cycle threshold (Ct) <35 were considered adequate for further virological analysis. Influenza viruses (IVs), respiratory syncytial virus (RSV), and rhinovirus (RV) genomes were detected by in-house real-time RT-PCR. All samples were positive to RNP detection with Ct <35. The mean Ct value was similar in the two groups (group 1 vs. group 2: 25.93 ± 2.22 vs. 25.46 ± 2.40; p = 0.10). IVs, RSV, and RV positivity rates were 26.7 vs. 52.7% ( p < 0.01), 7.6 vs. 9.9% ( p = 0.52), and 21.4 vs. 19.9% ( p = 0.76), respectively. Self-sampled OP swabs resulted as valid as GP-sampled OP swabs for molecular detection of respiratory viruses. Self-swabbing can thus be a worthwhile strategy for sample collection to implement molecular surveillance of respiratory pathogens and carry out epidemiological studies, easily reaching a larger population size., (Copyright © 2020 Galli, Pellegrinelli, Del Castillo, Forni, Gandolfi, Mosillo, Pietronigro, Tiwana, Castaldi and Pariani.)

Introduction: Online grooming is a manipulative process through which an adult attempts to arrange a sexual interaction with a minor using internet. Children are constantly exposed to the online world, posing online grooming as a public health issue., Objectives: The aim of this narrative review is to describe the state of online grooming preventive strategies in recent literature through an overview of online grooming phenomenon., Methods: Our literature review included research articles and reviews published between January 2014 and March 2019, as well as reference lists of included studies., Results: The analysis provides a picture of online grooming phenomenon, identify recurrent features of perpetrators and victims. Several preventive strategies have been implemented, but they lack any kind of efficacy evaluation and miss a theory driven approach. Fragmentation of preventive initiatives is a critical issue, in contrast with the need of an institutional public health strategy., Conclusions: While the attention around online grooming is growing, there is still the need of further sensitizing the involved stakeholders and developing evidence based preventive strategies under an institutional guidance.