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Introduction: Compared to old people who live at home, depressive symptoms are more prevalent in those who live in long-term care facilities (LTCFs). Different kinds of non-pharmacological treatment approaches in LTCFs have been studied, including behavioral and cognitive-behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy and life review/reminiscence. The aim of the current review was to systematically review non-pharmacological treatments used to treat depressed older adults with no or mild cognitive impairment (as described by a Mini Mental State Examination score > 20) living in LTCFs.Methods: A research was performed on PubMed and Scopus databases. Following the Preferred Reporting Items for Systematic Reviews and MetaAnalyses (PRISMA) flowchart, studies selection was made. The quality of each Randomized Controlled Trial was scored using the Jadad scale, Quasi-Experimental Design studies and Non-Experimental studies were scored based on the Newcastle-Ottawa Scale (NOS)Results: The review included 56 full text articles; according to the type of intervention, studies were grouped in the following areas: horticulture/gardening (n = 3), pet therapy (n = 4), physical exercise (n = 9), psychoeducation/rehabilitation (n = 15), psychotherapy (n = 3), reminiscence and story sharing (n = 14), miscellaneous (n = 8).Discussion and Conclusion: Despite mixed or negative findings in some cases, most studies included in this systematic review reported that the non-pharmacological interventions assessed were effective in the management of depressed elderly in the LTCFs context. Regrettably, the limitations and heterogeneity of the studies described above hinder the possibility to generalize and replicate results.

INTRODUCTION: Clinical Networks are complex interventions that enable healthcare professionals from various disciplines to work in a coordinated manner in the context of multiple care settings, to provide a high quality response to a specific disease. The aim of this study was to evaluate if clinical networks are able to improve effectiveness, efficiency, patients' satisfaction and professionals' behavior in the health care settings, namely the "quadruple aim" quality goals. MATERIALS AND METHODS: A systematic review of documents published until February 28, 2018, in Medline, Embase and CINAHL was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach. A specific research strategy was created to identify studies evaluating effectiveness, efficiency, patient satisfaction and professionals well-being obtained through clinical networks implementation. RESULTS: 14249 studies were identified; 12 of these were eligible to the evaluation of "Quadruple Aim" outcomes. 9 studies focused on patients' outcomes improvement and 4 on network efficiency. Professionals' and patients' experience were not considered in any study. CONCLUSIONS: There are some evidences that clinical network can improve patients' outcomes and health funds allocation in a small number of moderate-low quality studies. Further rigorous studies are needed to confirm these findings and to evaluate patients' and professionals' experience, taking into account also networks' structural features that could influence outcomes achievement. ispartof: Journal of Healthcare Quality Research vol:34 issue:1 pages:29-39 ispartof: location:Spain status: published

The neurovascular unit (NVU) is a relatively recent concept that clearly describes the relationship between brain cells and their blood vessels. The components of the NVU, comprising different types of cells, are so interrelated and associated with each other that they are considered as a single functioning unit. For this reason, even slight disturbances in the NVU could severely affect brain homeostasis and health. In this review, we aim to describe the current state of knowledge concerning the role of oxidative stress on the neurovascular unit and the role of a single cell type in the NVU crosstalk.

Workforce aging is becoming a significant public health problem due to the resulting emergence of age-related diseases, such as osteoporosis. The prevention and early detection of osteoporosis is important to avoid bone fractures and their socio-economic burden. The aim of this study is to evaluate the sustainability of a screening workplace program able to detect workers with osteoporosis. The screening process included a questionnaire-based risk assessment of 1050 healthcare workers followed by measurement of the bone mass density (BMD) with a pulse-echo ultrasound (PEUS) at the proximal tibia in the at-risk subjects. Workers with a BMD value ≤ 0.783 g/cm² were referred to a specialist visit ensuring a diagnosis and the consequent prescriptions. Any possible association between the outcome variable BMD ≤ 0.783 g/cm² and the risk factors was evaluated. The costs were calculated with a full costing method. We identified 60 pathological subjects. We observed increased risks for women, older ages, and menopause (p < 0.01). The yearly cost of our screening program estimated for this study was 8242 euros, and, considering the fragility bone fracture costs, we hypothesize a considerable economic savings, with a possible positive benefits/cost ratio of 2.07. We can say that the margin between the investment and results leads to a preference for this type of screening program. Osteoporosis is an occupational health problem, and a workplace screening program could be a cost-effective intervention. ispartof: INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH vol:18 issue:3 ispartof: location:Switzerland status: published

Introduction Fasting can be defined as abstinence or reduction from food, drink, or both, for a defined period. There are many different types of fasting regimens, such as Ramadan fasting, intermittent fasting, Christian Orthodox fasting. The aim of this overview is to provide an exhaustive summary on the beneficial effects and harms associated with fasting regimens and discuss mechanisms by which this non-pharmacological approach might lead to improve human health. Evidence acquisition A systematic search was performed on MEDLINE (PubMed), Embase, Cochrane Library and CINHAL. We included systematic reviews (SRs) that report on impact of different types of fasting regimens on health. Selection of SRs, data extraction and quality assessment were undertaken in duplicate. Evidence synthesis A total of 21 SRs were included. Cumulatively, 97 health outcomes were identified. Of them, cardiovascular risk factors were the most frequently analyzed. Ramadan fasting is associated with significant improvements in body weight and visceral lean mass, high-density lipoprotein cholesterol (HDL-c), and with reductions in low-density lipoprotein cholesterol (LDL-c) and total cholesterol (T-chol), especially in cardiac patients. Similarly, reviews on Intermittent and Orthodox fasting proved benefits of those on weight, BMI, lipidic and glucose profile, inflammatory markers. Conclusions Fasting regimens showed potential beneficial effects on several health indicators in adult populations. Nevertheless, evidence on some specific health dimensions (cognitive function, well-being, quality of life) is limited. Thus, in the future, further RCTs or cohort studies with good methodological quality and larger sample sizes are warranted to better understand the underlying biological mechanism and the benefits on multidimensional aspects of health.

Endogenous antioxidants protect cells from reactive oxygen species (ROS)-related deleterious effects, and an imbalance in the oxidant/antioxidant systems generates oxidative stress. Glyoxalase 1 (GLO1) is a ubiquitous cellular enzyme involved in detoxification of methylglyoxal (MG), a cytotoxic byproduct of glycolysis whose excess can produce oxidative stress. In retinitis pigmentosa, one of the most diffuse cause of blindness, oxidative damage leads to photoreceptor death. To clarify the role of GLO1 in retinitis pigmentosa onset and progression, we treated human retinal pigment epithelium cells by the oxidant agent A2E. Transcriptome profiles between treated and untreated cells were performed by RNA-Seq, considering two time points (3 and 6 h), after the basal one. The exposure to A2E highlighted significant expression differences and splicing events in 370 GLO1 first-neighbor genes, and 23 of them emerged from pathway clustered analysis as main candidates to be associated with retinitis pigmentosa. Such a hypothesis was corroborated by the involvement of previously analyzed genes in specific cellular activities related to oxidative stress, such as glyoxylate and dicarboxylate metabolism, glycolysis, axo-dendritic transport, lipoprotein activity and metabolism, SUMOylation and retrograde transport at the trans-Golgi network. Our findings could be the starting point to explore unclear molecular mechanisms involved in retinitis pigmentosa etiopathogenesis.

Oxidative stress represents one of the principal inductors of lifestyle-related and genetic diseases. Among them, inherited retinal dystrophies, such as age-related macular degeneration and retinitis pigmentosa, are well known to be susceptible to oxidative stress. To better understand how high reactive oxygen species levels may be involved in retinal dystrophies onset and progression, we performed a whole RNA-Seq experiment. It consisted of a comparison of transcriptomes&rsquo, profiles among human retinal pigment epithelium cells exposed to the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering two time points (3h and 6h) after the basal one. The treatment with A2E determined relevant differences in gene expression and splicing events, involving several new pathways probably related to retinal degeneration. We found 10 different clusters of pathways involving differentially expressed and differentially alternative spliced genes and highlighted the sub- pathways which could depict a more detailed scenario determined by the oxidative-stress-induced condition. In particular, regulation and/or alterations of angiogenesis, extracellular matrix integrity, isoprenoid-mediated reactions, physiological or pathological autophagy, cell-death induction and retinal cell rescue represented the most dysregulated pathways. Our results could represent an important step towards discovery of unclear molecular mechanisms linking oxidative stress and etiopathogenesis of retinal dystrophies.

Long non-coding RNAs (lncRNAs) are untranslated transcripts which regulate many biological processes. Changes in lncRNA expression pattern are well-known related to various human disorders, such as ocular diseases. Among them, retinitis pigmentosa, one of the most heterogeneous inherited disorder, is strictly related to oxidative stress. However, little is known about regulative aspects able to link oxidative stress to etiopathogenesis of retinitis. Thus, we realized a total RNA-Seq experiment, analyzing human retinal pigment epithelium cells treated by the oxidant agent N-retinylidene-N-retinylethanolamine (A2E), considering three independent experimental groups (untreated control cells, cells treated for 3 h and cells treated for 6 h). Differentially expressed lncRNAs were filtered out, explored with specific tools and databases, and finally subjected to pathway analysis. We detected 3,3&rsquo, overlapping ncRNAs, 107 antisense, 24 sense-intronic, four sense-overlapping and 227 lincRNAs very differentially expressed throughout all considered time points. Analyzed lncRNAs could be involved in several biochemical pathways related to compromised response to oxidative stress, carbohydrate and lipid metabolism impairment, melanin biosynthetic process alteration, deficiency in cellular response to amino acid starvation, unbalanced regulation of cofactor metabolic process, all leading to retinal cell death. The explored lncRNAs could play a relevant role in retinitis pigmentosa etiopathogenesis, and seem to be the ideal candidate for novel molecular markers and therapeutic strategies.

Molecular signalling that leads to brain arteriovenous malformation (bAVM) is to date elusive and this is firstly due to the low frequency of familial cases. Conversely, sporadic bAVM is the most diffuse condition and represents the main source to characterize the genetic basis of the disease. Several studies were conducted in order to detect both germ-line and somatic mutations linked to bAVM development and, in this context, Next Generation Sequencing technologies offer a pivotal resource for the amount of outputted information. We performed Whole Exome Sequencing on a young boy affected by sporadic bAVM. Paired-end sequencing was conducted on an Illumina platform and filtered variants were validated by Sanger sequencing. We detected 20 Likely Gene-Disrupting variants affecting as many loci. Of these variants, 11 are inherited novel variants and one is a de novo nonsense variant, affecting STK4 gene. Moreover, we also considered rare known variants affecting loci involved in vascular differentiation. In order to explain their possible involvement in bAVM pathogenesis, we analysed molecular networks at Cytoscape platform. In this study we focus on some genetic point variations detected in a child affected by bAVM. Therefore, we suggest these novel affected loci as prioritized for further investigation on pathogenesis of bAVM lesions.

Objective To identify the prevalence of the practice of defensive medicine among Italian hospital physicians, its costs and the reasons for practising defensive medicine and possible solutions to reduce the practice of defensive medicine. Methods Cross-sectional web survey. Main outcome measures Number of physicians reporting having engaged in any defensive medicine behaviour in the previous year. Results A total of 1313 physicians completed the survey. Ninety-five per cent believed that defensive medicine would increase in the near future. The practice of defensive medicine accounted for approximately 10% of total annual Italian national health expenditure. Conclusions Defensive medicine is a significant factor in health care costs without adding any benefit to patients. The economic burden of defensive medicine on health care systems should provide a substantial stimulus for a prompt review of this situation in a time of economic crisis. Malpractice reform, together with a systematic use of evidence-based clinical guidelines, is likely to be the most effective way to reduce defensive medicine.

INTRODUCTION: Defensive medicine (DM) is used when a doctor deviates from good practices to prevent complaints from patients or caregivers. This is a structured phenomenon that may not only affect the physician, but all healthcare personnel. The aim of this review was to determine whether DM is also performed by Non-Medical Health Professionals (NMHP), and the reasons, features, and effects of NMHP-DM. MATERIALS AND METHODS: The review was conducted according to PRISMA guidelines, and specific inclusion criteria were used to search for relevant documents published up to 12 April 2018 in the main biomedical databases. RESULTS: A total of 91 potentially relevant studies were identified. After the removal of duplicates, 72 studies were screened for eligibility, separately by two of the authors. Finally, 14 qualitative and quantitative studies were considered relevant for the purpose of the present review. These last studies were assessed for their methodological quality. CONCLUSIONS: NMHP-DM is quite similar to DM practiced by doctors, and is mainly caused by fear of litigation. Midwives and nursing personnel practiced both active and passive DM, such as over-investigation, over-treatment, and avoidance of high-risk patients. NMHP-DM could increase risks for patient health, costs, risk of burnout for healthcare employees. Further studies are needed to better understand prevalence and features of NMHP-DM in all health professional fields, in order to apply appropriate preventive strategies to contrast DM among health care personnel. ispartof: Journal of Healthcare Quality Research vol:34 issue:2 pages:97-108 ispartof: location:Spain status: published

Background: Retinitis pigmentosa punctata albescens (RPA) is a particular form of retinitis pigmentosa characterized by childhood onset night blindness and areas of peripheral retinal atrophy. We investigated the genetic cause of RPA in a family consisting of two affected Egyptian brothers with healthy consanguineous parents. Methods: Mutational analysis of four RPA causative genes was realized by Sanger sequencing on both probands, and detected variants were subsequently genotyped in their parents. Afterwards, found variants were deeply, statistically, and in silico characterized to determine their possible effects and association with RPA. Results: Both brothers carry three missense PRPH2 variants in a homozygous condition (c.910C &gt, A, c.929G &gt, A, and c.1013A &gt, C) and two promoter variants in RHO (c.-26A &gt, G) and RLBP1 (c.-70G &gt, A) genes, respectively. Haplotype analyses highlighted a PRPH2 rare haplotype variant (GAG), determining a possible alteration of PRPH2 binding with melanoregulin and other outer segment proteins, followed by photoreceptor outer segment instability. Furthermore, an altered balance of transcription factor binding sites, due to the presence of RHO and RLBP1 promoter variants, might determine a comprehensive downregulation of both genes, possibly altering the PRPH2 shared visual-related pathway. Conclusions: Despite several limitations, the study might be a relevant step towards detection of novel scenarios in RPA etiopathogenesis.

Background Autosomal recessive forms of retinitis punctata albescens (RPA) have been described. RPA is characterized by progressive retinal degeneration due to alteration in visual cycle and consequent deposit of photopigments in retinal pigment epithelium. Five loci have been linked to RPA onset. Among these, the retinaldehyde-binding protein 1 gene, RLBP1, is the most frequently involved and several founder mutations were reported. We report results of a genetic molecular investigation performed on a large Sicilian family in which appears a young woman with RPA. Results The proband is in homozygous condition for a novel RLBP1 single-pair deletion, and her healthy parents, both heterozygous, are not consanguineous. Thenovelc.398delC (p.P133Qfs*258) involves the exon 6 and leads to a premature stop codon, resulting in a truncated protein entirely missing of CRAL-TRIO lipid-binding domain. Pedigree analysis showed other non-consanguineous relatives heterozygous for the same mutation in the family. Extension of mutation research in the native town of the proband revealed its presence also in healthy subjects, in a heterozygous condition. Conclusions A novel RLBP1 truncating mutation was detected in a young girl affected by RPA. Although her parents are not consanguineous, the mutation was observed in a homozygous condition. Being them native of the same small Sicilian town of Fiumedinisi, the hypothesis of a geographical area-related mutation was assessed and confirmed.

Cerebral cavernous malformations (CCMs) are clusters of capillaries in the brain that may cause focal deficits or seizures in affected patients. They occur in both sporadic and inherited autosomal dominant form. Germline mutations in CCM1, CCM2 and CCM3 were identified in familial cases. Over the past 13 years we performed sequencing and MLPA of the CCM genes in all sporadic and familial CCM cases coming from some hospital clinics of Neurology and Neurosurgery of Messina and other Italian cities. Our results showed that CCM sporadic patients, negative for previously reported CCM gene causative mutations, always carried known CCM polymorphisms. Previously, we reported polymorphisms in CCM2 gene associated with an increase in risk for CCM. Here, we undertook a case-control study to investigate the possible association of others polymorphisms (c.485 + 65 C/G, c.989 + 63 C/G, c.1980 A/G in CCM1 gene, c.472 + 127 C/T in CCM2 and c.150 G/A in CCM3) with CCMs. The five polymorphisms were characterized in 64 sporadic patients and in 90 healthy controls by ASO-PCR. Statistically significant differences in frequencies between patients and controls were found for c.485 + 65C/G, c.1980 A/G and c.472 + 127C/T polymorphisms. For c.485 + 65C/G polymorphism, a higher frequency of mutated allele (G) was found in patients group (9%) than in controls (2%) (p = 0.0041); for c.1980 A/G polymorphism, we found a frequency of mutated allele (G) higher in the control group (25%) compared to that of patients (8%) (p = 0.0396). Same trend was observed for c.472 + 127C/T polymorphism (T allele frequency = 34% and 6% in control group and patients, respectively; p = 0.0001). Polymorphisms c.485 + 65C/G, c.1980 A/G and c.472 + 127C/T were associated with an increased risk of CCM as indicated by odds ratio values. Furthermore, c.1980 A/G and c.472 + 127C/T polymorphisms were associated with less severe CCM symptomatology. Identification of these polymorphisms in CCM sporadic patient may represent a useful tool for clinicians to determine prognosis, scheduled periodic checks and appropriate treatment strategy.

To orchestrate the genomic response to cellular stress signals, p53 recognizes and binds to DNA containing specific and well-characterized p53-responsive elements (REs). Differences in RE sequences can strongly affect the p53 transactivation capacity and occur even between closely related species. Therefore, the identification and characterization of a species-specific p53 Binding sistes (BS) consensus sequence and of the associated target genes may help to provide new insights into the evolution of the p53 regulatory networks across different species. Although p53 functions were studied in a wide range of species, little is known about the p53-mediated transcriptional signature in Danio rerio. Here, we designed and biochemically validated a computational approach to identify novel p53 target genes in Danio rerio genome. Screening all the Danio rerio genome by pattern-matching-based analysis, we found p53 RE-like patterns proximal to 979 annotated Danio rerio genes. Prioritization analysis identified a subset of 134 candidate pattern-related genes, 31 of which have been investigated in further biochemical assays. Our study identified runx1, axin1, traf4a, hspa8, col4a5, necab2, and dnajc9 genes as novel direct p53 targets and 12 additional p53-controlled genes in Danio rerio genome. The proposed combinatorial approach resulted to be highly sensitive and robust for identifying new p53 target genes also in additional animal species., This work was supported by Associazione Italiana per la Ricerca sul Cancro (AIRC, IG #14078), Ricerca Corrente 2014–16 granted by the Italian Ministry of Health, and the “5 × 1000” voluntary contributions to G.M., Ricerca Finalizzata 2011 granted by the Italian Ministry of Health to L.M. and partly supported by Ministero dell’Istruzione, dell’Università e della Ricerca (MIUR) ex-60% funds to M.M., E.M. end G.B.

Background Defensive medicine affects healthcare systems worldwide. The concerns and perception about medical liability could lead practitioners to practise defensive medicine. Second victim is a healthcare worker involved in an unanticipated adverse patient event. The role of being second victim and the other possible determinants for defensive medicine is mostly unclear. Objective To study the condition of being second victim as a possible determinants of defensive medicine among Italian hospital physicians. Design, setting and participants A secondary analysis of the database of the national survey study on the prevalence and the costs of defensive medicine in Italy that was carried out between April 2014 and June 2014 in 55 Italian hospitals was performed for this study. The demographic section of the questionnaire was selected including the physician's age, gender, specialty, activity volume, grade and the variable being a second victim after an adverse event. Results A total sample of 1313 physicians (87.5% response rate) was used in the data analyses. Characteristics of the participants included a mean age 49.2 of years and 19.4 average years of experience. The most prominent predictor for practising defensive medicine was the physicians’ experience of being a second victim after an adverse event (OR = 1.88; 95%CI, 1.38–2.57). Other determinants included age, years of experience, activity volume and risk of specialty. Conclusions Malpractice reform, effective support to second victims in hospitals together with a systematic use of evidence-based clinical guidelines, emerged as possible recommendations for reducing defensive medicine.

Introduction The healthcare worker involved in an unanticipated adverse patient event can become second victim. These workers suffer physically and psycho-socially and try to overcome the post-event emotional stress by obtaining emotional support in a variety of ways. The goal of this research was to study second victims among health care providers in Italy. Methods This contribution contains the results of 33 interviews of nurses, physicians and other healthcare workers. After institutional approval, the semi-structured interview, composed of 25 questions, was translated from English into Italian. The audio-interviews were transcribed on paper verbatim by the interviewer. It was then verified if the interviewees experienced the six post-event stages of second victim recovery previously described within the literature. Results The interviewees described the post-event recovery stages described by literature but stages were not detailed in the exact succession order as the American study. All participants clearly remembered the adverse event and referred the physical and psycho-social symptoms. The psychological support obtained by second victims was described as poor and inefficient. Discussion The post-event recovery pathway is predictable but not always clearly respected as defined within this Italian sample. Future study of the second-victim phenomenon and desired supportive interventions is necessary to understand the experience and interventions to mitigate harm of future clinicians. Every day healthcare workers become second victims and, considering that human resources are the most important heritage of healthcare infrastructures, after an adverse event it is very important to execute valid interventional programs to support and train these workers.