Hyperbaric oxygen therapy improves the osteogenic and vasculogenic properties of mesenchymal stem cells in the presence of inflammation in vitro

Hyperbaric oxygen (HBO) therapy has been reported to be beneficial for treating many conditions of inflammation-associated bone loss. The aim of this work was to in vitro investigate the effect of HBO in the course of osteogenesis of human Mesenchymal Stem Cells (MSCs) grown in a simulated pro-inflammatory environment. Cells were cultured with osteogenic differentiation factors in the presence or not of the pro-inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), and simultaneously exposed daily for 60 min, and up to 21 days, at 2,4 atmosphere absolute (ATA) and 100% O2. To elucidate osteogenic differentiation-dependent effects, cells were additionally pre-committed prior to treatments. Cell metabolic activity was evaluated by means of the MTT assay and DNA content quantification, whereas osteogenic and vasculogenic differentiation was assessed by quantification of extracellular calcium deposition and gene expression analysis. Metabolic activity and osteogenic properties of cells did not differ between HBO, high pressure (HB) alone, or high oxygen (HO) alone and control if cells were pre-differentiated to the osteogenic lineage. In contrast, when treatments started contextually to the osteogenic differentiation of the cells, a significant reduction in cell metabolic activity first, and in mineral deposition at later time points, were observed in the HBO-treated group. Interestingly, TNF-α supplementation determined a significant improvement in the osteogenic capacity of cells subjected to HBO, which was not observed in TNF-α-treated cells exposed to HB or HO alone. This study suggests that exposure of osteogenic-differentiating MSCs to HBO under in vitro simulated inflammatory conditions enhances differentiation towards the osteogenic phenotype, providing evidence of the potential application of HBO in all those processes requiring bone regeneration

La psichiatria di consultazione e collegamento nell’ospedale generale: l’esperienza perugina

Objective - This study describes the Consultation-Liaison Service of the Perugia University and investigates the significant associations between a many variables of the assessed population. Results - During the time from July 2008 to June 2009, 722 consultations were performed at the general hospital in Perugia. First examinations were 605. Most consultations involved European patients (95,2%) of female gender (56.3%); mean age was 55.77 (SD ± 21.27). Emergencies were 22.5%; one fifth of patients were not informed of having been referred to our service and half of interventions were requested by departments of internal medicine. The primary reasons for the referral were depression (18.6%), unexplained physical symptoms (12.3%) and anxiety (10.4%); most patients were already taking psychotropic medication before our intervention (58.8%).The significant associations are the following: associations between gender and social status (p < 0.01), social condition (p < 0.01), work (p < 0.01) and advice about the need of the consultation (p < 0.05). The area (medical, surgical and specialized area) are related with the advice (p < 0.05), the reason (p < 0.01) and the type of the consultation (p < 0.01), the diagnostic explanations (p < 0.01), the liaison investigations (p < 0.01) and, at last, with the longrange plan after discharge (p < 0.01)

Air pollutants and daily number of admissions to psychiatric emergency services: evidence for detrimental mental health effects of ozone

Abstract Aims Aim of the current study is to investigate the associations between daily levels of air pollutants (particulate matter, ozone, carbon monoxide, nitrogen dioxide) and daily admissions for mental disorders to the emergency department of two general hospitals in Umbria region (Italy). Methods We collected data about daily admissions to psychiatric emergency services of two general hospitals, air pollutants' levels and meteorological data for the time period 1 January 2015 until 31 December 2016. We assessed the impact of an increase in air pollutants on the number of daily admissions using a time-series econometric framework. Results A total of 1860 emergency department admissions for mental disorders were identified. We observed a statistically significant impact of ozone levels on daily admissions. The estimated coefficient of O3 is statistically significant at the 1% level. All other pollutants were not significantly associated with the number of daily admissions. Conclusions Short-term exposure to ozone may be associated with increased psychiatric emergency services admissions. Findings add to previous literature on existing evidence for air pollution to have an impact on mental health. Ozone may be considered a potential environmental risk factor for impaired mental health

Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

<p>Abstract</p> <p>Background</p> <p>One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study.</p> <p>Methods/Design</p> <p>The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome.</p> <p>Discussion</p> <p>The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.</p> <p>Trial Registration</p> <p><b>Clincaltrials.gov Identifier</b>: NCT00395915</p

Role of the repeat expansion size in predicting age of onset and severity in RFC1 disease

RFC1 disease, caused by biallelic repeat expansion in RFC1, is clinically heterogeneous in terms of age of onset, disease progression and phenotype. We investigated the role of the repeat size in influencing clinical variables in RFC1 disease. We also assessed the presence and role of meiotic and somatic instability of the repeat. In this study, we identified 553 patients carrying biallelic RFC1 expansions and measured the repeat expansion size in 392 cases. Pearson’s coefficient was calculated to assess the correlation between the repeat size and age at disease onset. A Cox model with robust cluster standard errors was adopted to describe the effect of repeat size on age at disease onset, on age at onset of each individual symptoms, and on disease progression. A quasi-Poisson regression model was used to analyse the relationship between phenotype and repeat size. We performed multivariate linear regression to assess the association of the repeat size with the degree of cerebellar atrophy. Meiotic stability was assessed by Southern blotting on first-degree relatives of 27 probands. Finally, somatic instability was investigated by optical genome mapping on cerebellar and frontal cortex and unaffected peripheral tissue from four post-mortem cases. A larger repeat size of both smaller and larger allele was associated with an earlier age at neurological onset [smaller allele hazard ratio (HR) = 2.06, P < 0.001; larger allele HR = 1.53, P < 0.001] and with a higher hazard of developing disabling symptoms, such as dysarthria or dysphagia (smaller allele HR = 3.40, P < 0.001; larger allele HR = 1.71, P = 0.002) or loss of independent walking (smaller allele HR = 2.78, P < 0.001; larger allele HR = 1.60; P < 0.001) earlier in disease course. Patients with more complex phenotypes carried larger expansions [smaller allele: complex neuropathy rate ratio (RR) = 1.30, P = 0.003; cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) RR = 1.34, P < 0.001; larger allele: complex neuropathy RR = 1.33, P = 0.008; CANVAS RR = 1.31, P = 0.009]. Furthermore, larger repeat expansions in the smaller allele were associated with more pronounced cerebellar vermis atrophy (lobules I–V β = −1.06, P < 0.001; lobules VI–VII β = −0.34, P = 0.005). The repeat did not show significant instability during vertical transmission and across different tissues and brain regions. RFC1 repeat size, particularly of the smaller allele, is one of the determinants of variability in RFC1 disease and represents a key prognostic factor to predict disease onset, phenotype and severity. Assessing the repeat size is warranted as part of the diagnostic test for RFC1 expansion

Educazione Sanitaria odontostomatologica nella scuola: esperienza di un triennio

5nonenoneVANNINI A.; POZZI T.; QUARTESAN E.; MUGNAINI L.; GASPARINI R.Vannini, A.; Pozzi, Teresa; Quartesan, E.; Mugnaini, L.; Gasparini, R

Genes involved in Alzheimer's disease, a survey of possible candidates.

Alzheimer's disease (AD) is the major cause of dementia in the elderly. It is characterized by a progressive deterioration in memory and cognitive functions, but also behavioral symptoms are common. Many different genes are possibly involved in Alzheimer's Disease: four genetic factors were confirmed in different studies, while at least 50 additional genes were tested with contrasting results. A major aim both for clinician and researchers would be the identification of the genes involved in AD, to better understand the biological mechanism of this disease and consequently to develop appropriate treatments. The aim of this review is to explore genetics of AD