Roberta Delasta Lazzari

Genome-wide meta-analyses identify three loci associated with primary biliary cirrhosis

A genome-wide association screen for primary biliary cirrhosis risk alleles was performed in an Italian cohort. The results from the Italian cohort replicated IL12A and IL12RB associations, and a combined meta-analysis using a Canadian dataset identified newly associated loci at SPIB (P = 7.9 × 10−11, odds ratio (OR) = 1.46), IRF5-TNPO3 (P = 2.8 × 10−10, OR = 1.63) and 17q12-21 (P = 1.7 × 10−10, OR = 1.38).

Silybin combined with phosphatidylcholine and vitamin E in patients with nonalcoholic fatty liver disease: A randomized controlled trial

The only currently recommended treatment for nonalcoholic fatty liver disease (NAFLD) is lifestyle modification. Preliminary studies of silybin showed beneficial effects on liver function. Realsil (RA) comprises the silybin phytosome complex (silybin plus phosphatidylcholine) coformulated with vitamin E. We report on a multicenter, phase III, double-blind clinical trial to assess RA in patients with histologically documented NAFLD. Patients were randomized 1:1 to RA or placebo (P) orally twice daily for 12 months. Prespecified primary outcomes were improvement over time in clinical condition, normalization of liver enzyme plasma levels, and improvement of ultrasonographic liver steatosis, homeostatic model assessment (HOMA), and quality of life. Secondary outcomes were improvement in liver histologic score and/or decrease in NAFLD score without worsening of fibrosis and plasma changes in cytokines, ferritin, and liver fibrosis markers. We treated 179 patients with NAFLD; 36 were also HCV positive. Forty-one patients were prematurely withdrawn and 138 patients analyzed per protocol (69 per group). Baseline patient characteristics were generally well balanced between groups, except for steatosis, portal infiltration, and fibrosis. Adverse events (AEs) were generally transient and included diarrhea, dysgeusia, and pruritus; no serious AEs were recorded. Patients receiving RA but not P showed significant improvements in liver enzyme plasma levels, HOMA, and liver histology. Body mass index normalized in 15% of RA patients (2.1% with P). HCV-positive patients in the RA but not the P group showed improvements in fibrogenesis markers. This is the first study to systematically assess silybin in NAFLD patients. Treatment with RA but not P for 12 months was associated with improvement in liver enzymes, insulin resistance, and liver histology, without increases in body weight. These findings warrant further investigation.

Y chromosome loss in male patients with primary biliary cirrhosis.

Sex chromosome abnormalities have been advocated to be involved in the striking female prevalence of primary biliary cirrhosis (PBC) and women with PBC manifest an increased X chromosome loss in peripheral blood mononuclear cells compared to age-matched healthy women. Our knowledge of the etiopathogenesis of autoimmunity in male patients remains, however, limited. Next to the possible role of androgens and their imbalances, the Y chromosome appears as a potential candidate for influence of the immune function in men. Herein we analyzed a population of male patients with primary biliary cirrhosis (n = 26) and healthy controls (n = 88) to define a potential association of disease and the loss of the Y chromosome. We demonstrate that Y chromosome loss indeed is higher in PBC males compared to healthy controls, and this phenomenon increases with aging. We were, thus, able to confirm the existence of an analogous mechanism in the male population to previously identified X haploinsufficiency in female patients with organ-specific autoimmune disease. We propose that this commonality might represent a relevant feature in the etiopathogenesis of autoimmune diseases that should be further investigated.

Effect of Ankle-foot Orthosis on Gait Velocity and Cadence of Stroke Patients: A Systematic Review

[Purpose] The aim of the present study was to analyze the effect of an ankle-foot orthosis on gait variables (velocity and cadence) of stroke patients. To do this, a systematic review was conducted of four databases. [Subjects and Methods] The papers identified were evaluated based on the following inclusion criteria: 1) design: controlled, clinical trial; 2) population: stroke patients; 3) intervention: analysis of spatiotemporal variables of gait with an ankle-foot orthosis; 4) control group with different intervention or no intervention; and 5) outcome: improvement in gait velocity or cadence. [Results] Thirteen controlled trials addressing the effect of an ankle-foot orthosis on gait variables of stroke patients were found. They exhibited methodological quality of 3 or more points on the PEDro scale. [Conclusion] While the findings suggest the benefits of an AFO regarding gait velocity, the impact of this type of orthosis on cadence remains inconclusive. Thus, there is a need for further well-designed randomized, controlled, clinical trials to establish better scientific evidence for the effects of AFO usage on gait variables of stroke patients.

Effect of a single session of transcranial direct-current stimulation combined with virtual reality training on the balance of children with cerebral palsy: a randomized, controlled, double-blind trial.

[Purpose] The aim of the present study was to investigate the effects of a single session of transcranial direct current stimulation combined with virtual reality training on the balance of children with cerebral palsy. [Subjetcs and Methods] Children with cerebral palsy between four and 12 years of age were randomly allocated to two groups: an experimental group which performed a single session of mobility training with virtual reality combined with active transcranial direct current stimulation; and a control group which performed a single session of mobility training with virtual reality combined with placebo transcranial direct current stimulation. The children were evaluated before and after the training protocols. Static balance (sway area, displacement, velocity and frequency of oscillations of the center of pressure on the anteroposterior and mediolateral axes) was evaluated using a force plate under four conditions (30-second measurements for each condition): feet on the force plate with the eyes open, and with the eyes closed; feet on a foam mat with the eyes open, and with the eyes closed. [Results] An increase in sway velocity was the only significant difference found. [Conclusion] A single session of anodal transcranial direct current stimulation combined with mobility training elicited to lead to an increase in the body sway velocity of children with cerebral palsy.

Intrahepatic cholestasis of pregnancy: new insights into its pathogenesis

Absract Aim: To search a specific gene expression profile in women with intrahepatic cholestasis of pregnancy (ICP) and to evaluate the maternal and foetal outcome. Methods: We consecutively enrolled 12 women with ICP and 12 healthy pregnant controls. The gene expression profile was assayed with the microarray technique including a panel of 5541 human genes. Microarray data were validated by real-time PCR technique. Results: Caesarean delivery was performed in eight patients with ICP versus three controls (p = 0.05). ICP women delivered at earlier gestational age than control (p < 0.001). Foetal distress was recorded in two babies, but we failed to find any correlation between bile salt concentration and foetal distress. Twenty genes potentially correlated with ICP were found differentially expressed (p < 0.05). Among these, three belong to genetic classes involved in pathogenic mechanisms of ICP: (1) pathophysiology of pruritus (GABRA2, cases versus controls = 2, upregulated gene); (2) lipid metabolism and bile composition (HLPT, cases versus controls = 0.6, down-regulated gene) and (3) protein trafficking and cytoskeleton arrangement (KIFC3, cases versus controls = 0.5, down-regulated gene). Conclusions: Different gene expression may contribute to the complex pathogenesis of ICP. An upregulation of GABRA2 receptor may indicate that GABA may play a role in the pathogenesis of pruritus in this condition.

Upper limb function evaluation scales for individuals with cerebral palsy: a systematic review.

[Purpose] The aim of the present study was to perform a systematic review of the literature on the scales and methods most often used for the evaluation of upper limb function in individuals with cerebral palsy. [Materials and Methods] Searches were conducted in the Medline, PEDro, Lilacs, Scielo, and PubMed databases. The following inclusion criteria were used for the selection of articles: randomized controlled study, evaluation of upper limb function in individuals with cerebral palsy, and publication between 2006 and 2014. The methodological quality of the articles was evaluated using the PEDro evidence scale. [Results] Five articles met the inclusion criteria and achieved 6 points or higher on the PEDro scale of methodological quality. [Conclusion] The studies analyzed used different evaluation scales, but no consensus has been reached thus far on which scale is the most appropriate. Thus, further studies are needed to establish an adequate method for the evaluation of upper limb function in individuals with cerebral palsy.

Seroepidemiology of Polioviruses among University Students in Northern Italy

ABSTRACT The widespread use of poliovirus vaccination schemes has led to a marked decline in the incidence of paralytic poliomyelitis worldwide, but wild poliovirus is still endemic in some developing countries, and in 2009 a total of 23 countries reported at least 1 case of poliomyelitis caused by wild-strain polio viruses. A serological survey was thus conducted on the immunological status against polioviruses of 318 young adults, classified by their country of origin. Immunity to poliomyelitis was assessed by neutralizing antibody titration in tissues cultured on microplates. The rate of seronegativity (≤1:8) in the study population was 26.7% for poliovirus type 1, 7.2% for type 2, and 22.6% for type 3. In our sample of 318 individuals, 219 (68.9%) were Italian and 99 (31.1%) were from outside the European Union (EU). The proportion of cases found seropositive to polioviruses 1 and 3 decreased significantly with older age; this age-related decrease was more evident in the Italian group than among the non-EU subjects. Any risk of the wild virus recurring and causing paralytic poliomyelitis must be prevented, keeping Europe polio free by means of appropriate immunological protection, until polio has been conclusively eradicated all over the world. Judging from our findings, it may be worth considering administering a fifth dose of polio vaccine to adolescents.

Kinematic upper limb evaluation of children and adolescents with cerebral palsy: a systematic review of the literature

[Purpose] The aim of the present study was to perform a review of the literature on objective measures of upper limb movements in children and adolescents with cerebral palsy and describe the methods used to investigate upper limb kinematics in this population. [Materials and Methods] An extensive database search was performed using the keywords kinematics, upper limb, and cerebral palsy. A total of 146 papers were identified, but only five met the inclusion criteria. [Results] No consensus was found regarding the data collection, processing, and analysis procedures or reporting of the results. [Conclusion] Standardization of the protocol for 3D upper limb movement analysis will provide the foundation for comparable, reproducible results and eventually facilitate the planning of treatment interventions.

A surveillance system of Invasive Pneumococcal Disease in North-Eastern Italy.

BACKGROUND From 2007, in the Veneto Region (Italy), a surveillance system for invasive pneumococcal diseases (IPD) was implemented to estimate the regional epidemiology of IPD and to evaluate the impact of 13-valent pneumococcal conjugate vaccine (PCV13) vaccination. METHODS Data were collected from 2007 to 2014 and the total, annual and age-specific IPD notification rates were calculated. A Poisson regression model was used to identify the possible risk factors for developing IPD. RESULTS A total of 713 IPD cases were notified and the overall IPD notification rate was equal to 2.0 cases per 100,000 population (95% CI: 1.7-2.1), with an increasing trend between 2007 and 2014. The pneumococcal serotypes were identified in 608 (85.3%) isolates from biological specimens, and the most distributed serotypes were those contained in PCV13. Children <5 year-old and the adults over 65 year-old showed the highest PCV13 vaccine-type IPD notification rate, equal to 2.7/100,000 and 2.8/100,000, respectively. The risk to develop IPD was greater in children aged <5 years (RR = 8.9, 95% CI: 5.1-15.9; p<0.0001) and in adults aged >65 years (RR = 4.3, 95% CI: 2.7-6.9; p<0.0001), especially in males > 65 years of age (RR = 1.7, 95% CI: 1.0-2.8; p = 0.042). The invasive pneumococcal disease was mainly caused by the PCV13 serotypes (RR = 2.9, 95%CI: 2.3-3.9; p<0.0001), principally after the PCV13 introduction (RR = 2.3, 95% CI: 1.4-3.8; p<0.001). In spite of that, a significant reduction of the overall IPD incidence is evident in the period following the PCV13 vaccine introduction (RR = 0.4, 95% CI: 0.3-0.5; p<0.0001), particularly in children aged <5 years (RR = 0.3, 95% CI: 0.2-0.7; p = 0.002), demonstrating the real efficacy of PCV13 immunization for children. CONCLUSIONS In the Veneto Region, the surveillance system has allowed to describe the detailed epidemiological profile of invasive pneumococcal disease, pointing out that the most circulating pneumococcal serotypes were those contained in the PCV13 vaccine.