Autophagy and mitophagy biomarkers are reduced in sera of patients with Alzheimer's disease and mild cognitive impairment

Dementia is a neurocognitive disorder characterized by a progressive memory loss and impairment in cognitive and functional abilities. Autophagy and mitophagy are two important cellular processes by which the damaged intracellular components are degraded by lysosomes. To investigate the contribution of autophagy and mitophagy in degenerative diseases, we investigated the serum levels of specific autophagic markers (ATG5 protein) and mitophagic markers (Parkin protein) in a population of older patients by enzyme-linked immunosorbent assay. Two hundred elderly (≥65 years) outpatients were included in the study: 40 (20 F and 20 M) with mild-moderate late onset Alzheimer's disease (AD); 40 (20 F and 20 M) affected by vascular dementia (VAD); 40 with mild cognitive impairment (MCI); 40 (20 F and 20 M) with "mixed" dementia (MD); 40 subjects without signs of cognitive impairment were included as sex-matched controls. Our data indicated that, in serum samples, ATG5 and Parkin were both elevated in controls, and that VAD compared with AD, MCI and MD (all p < 0.01). Patients affected by AD, MD, and MCI showed significantly reduced circulating levels of both ATG5 and Parkin compared to healthy controls and VAD individuals, reflecting a significant down-regulation of autophagy and mitophagy pathways in these groups of patients. The measurement of serum levels of ATG5 and Parkin may represent an easily accessible diagnostic tool for the early monitoring of patients with cognitive decline

High GADA titer increases the risk of insulin requirement in LADA patients: a 7-year follow-up (NIRAD study 7)

ObjectiveThe aim of this study was to determine whether glutamic acid decarboxylase antibody (GADA) titer and other clinical parameters could define the risk of progression to insulin therapy in latent autoimmune diabetes in adults (LADA) patients during a 7-year follow-up.MethodsThis study involved 220 LADA and 430 type 2 diabetes subjects followed up for 7 years from the time of GADA screening to evaluate their progression toward insulin therapy. Kaplan–Meier curves and multivariate logistic regression analysis were performed to identify the markers capable of influencing this progression.ResultsDuring the follow-up, the drop out was 4% in both groups. A total of 119 (56.1%) out of 212 LADA patients required insulin during the 7 years of follow-up. The Kaplan–Meier plots showed that 74/104 (71.1%) of high GADA titer required insulin compared with 45/108 (41.6%) of low GADA titer and with 86/412 (20.9%) of type 2 diabetes (P&lt;0.0001 for both). A BMI of ≤25 kg/m2and IA-2ICand zinc transporter 8 (ZnT8) positivity were also shown as the markers of faster progression (P&lt;0.0001 for both). The proportion of LADA patients requiring insulin was significantly higher in the group of subjects treated also with sulfonylurea in the first year from diagnosis compared with those treated with diet and/or insulin sensitizers (P&lt;0.001). The multivariate analysis confirmed that the presence of high GADA titer was a significant predictor of insulin requirement (P&lt;0.0001, OR=6.95).ConclusionsHigh GADA titer, BMI ≤ 25, ZnT8 and IA-2ICpositivity and sulfonylurea treatment, in the first year from diagnosis, significantly increase the progression toward insulin requirement in LADA patients.</jats:sec

Effectiveness of a school-based multi-component smoking prevention intervention: the LdP cluster randomized controlled trial.

OBJECTIVE: We assessed the effectiveness of the Luoghi di Prevenzione-Prevention Grounds school-based smoking prevention programme. METHODS: We undertook a cluster randomized controlled trial of 989 students aged 14-15 years in 13 secondary schools located in Reggio Emilia, Italy. The intervention consisted of the "Smoking Prevention Tour" (SPT) out-of-school workshop, one in-depth lesson on one Smoking Prevention Tour topic, a life-skills peer-led intervention, and enforcement surveillance of school antismoking policy. Self-reported past 30-day smoking of ≥ 20 or 1-19 days of cigarette smoking (daily or frequent smoking, respectively) was recorded in 2 surveys administered immediately before and 18 months after the beginning of the programme. Analysis was by intention to treat. The effect of the intervention was evaluated using random effects logistic regression and propensity score-matching analyses. RESULTS: Past 30-day smoking and daily cigarette use at eighteen months follow-up were 31% and 46% lower, respectively, for intervention students compared to control students. Taking into account non-smokers at baseline only, daily smoking at eighteen months follow-up was 59% lower in intervention students than in controls. Past 30-day smoking in school areas was 62% lower in intervention students compared to controls. CONCLUSIONS: The Luoghi di Prevenzione-Prevention Grounds programme was effective in reducing daily smokers and in reducing smoking in school areas.This study was supported by Lega contro i Tumori (LILT), Reggio Emilia, Italy, by Public Health Service, Emilia-Romagna Region, and by Mental Health and Drug Addiction Service, Emilia-Romagna Regio

A prevention program for multiple health-compromising behaviors in adolescence: baseline results from a cluster randomized controlled trial.

OBJECTIVE: To describe the design and present the baseline findings of the evaluation study of 'Paesaggi di Prevenzione', a school-based prevention program tackling smoking, alcohol misuse, dietary risks, and physical inactivity in 12- to 14-year-olds. METHODS: The program was implemented from January 2011 to April 2012 in Emilia-Romagna, Italy, and comprised classroom activities and school-wide policies. A two-arm cluster randomized controlled trial was designed. Schools were the units of randomization and were matched by socioeconomic status, size, and type. RESULTS: Data from 4700 middle school students and 2952 high school students were collected anonymously from October to December 2010. Past-30-day smoking prevalence was 1.9% among middle school students and 20.8% among high school students. Past-30-day prevalence of alcohol intoxication was 2.2% among middle school students and 11.4% among high school students. A total of 39.7% of middle school students and 48.0% of high school students drank sugar-sweetened beverages four or more times per week; 7.5% of middle school students and 7.1% of high school students had intense physical activity every day. CONCLUSIONS: This study seems adequately powered and baseline variables appear evenly distributed between study groups. Findings are in line with those of the WHO Health Behaviour in School-Aged Children study.No specific funding was available for this study. The design and analysis of the study were assigned to external contractors, Avogadro University and the Cancer Prevention and Research Institute (ISPO), supported by the Italian League against Cancer (LILT), Reggio Emilia, Italy

A school-based peer-led smoking prevention intervention with extracurricular activities: the LILT-LdP cluster randomized controlled trial design and study population.

AIMS AND BACKGROUND: Few school programs are effective in preventing adolescents' tobacco smoking initiation. The "Lega contro i Tumori - Luoghi di Prevenzione" is a cluster randomized controlled trial designed to evaluate a school-based peer-led smoking prevention intervention with extracurricular activities for students aged 14-15 years. This paper presents the study design and the baseline characteristics of the study population. METHODS AND STUDY DESIGN: Twenty secondary schools located in the Reggio Emilia province took part in the study. Five schools were excluded because they already participated in smoking prevention interventions. The schools were randomized to control or intervention arms. The study population consisted of students attending the first grade. Components of the intervention included 1) the out-of-school "Smoking Prevention Tour" (SPT) at the "Luoghi di Prevenzione" Center, a 4-hour (4 sessions) extracurricular activity; 2) the "Smoke-free Schools" intervention, combining a life-skills-based peer-led intervention at school, an in-depth lesson on one of the SPT sessions, and enforcement surveillance of the school antismoking policy. Tobacco use was studied through a questionnaire administered before and 6 months after the intervention. RESULTS: Eleven high schools and 9 vocational secondary schools took part in the study for a total of 2,476 out of 3,050 eligible students (81.2%). The proportions of respondents in high schools and vocational secondary schools were 90.9% and 64.5%, respectively (P <0.001). Intervention and control arms showed a different distribution of gender and school type, whereas no difference was observed in any tobacco-use characteristic. CONCLUSIONS: This study is one of the few Italian trials to evaluate the effectiveness of a school-based program for preventing smoking initiation.This study was supported by Lega Italiana per la Lotta contro i Tumori (LILT) di Reggio Emilia, onlus, Reggio Emilia, Italy, by Public Health Service, Emilia-Romagna Region, and by Mental Health and Drug Addiction Service, Emilia-Romagna Regio

Primary Prophylaxis of Invasive Fungal Diseases in Allogeneic Stem Cell Transplantation: Revised Recommendations from a Consensus Process by Gruppo Italiano Trapianto Midollo Osseo (GITMO)

Abstract This document updates and expands the recommendations on primary prophylaxis of invasive fungal diseases (IFD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, published in 2009 by the Gruppo Italiano Trapianto Midollo Osseo (GITMO). A consensus process was undertaken to describe and evaluate current information and practice regarding risk stratification and primary antifungal prophylaxis during the pre-engraftment and postengraftment phases after allo-HSCT. The revised recommendations were based on the evaluation of recent literature including a large, prospective, multicenter epidemiological study of allo-HSCT recipients conducted among the GITMO transplantation centers during the period of 2008 to 2010. It is intended as a guide for the identification of types and phases of transplantation at low, standard, and high risk for IFD, according to the underlying disease, transplantation, and post-transplantation factors. The risk stratification was the critical determinant of the primary antifungal approach for allo-HSCT recipients

The effect of fruits and vegetables on urinary stone risk factors

The effect of fruits and vegetables on urinary stone risk factors.BackgroundThe overall effect of fruit and vegetable intake on urinary stone risk profile is not yet known.MethodsWe studied the effect of a two-week period of fruit and vegetable elimination on urinary stone risk profile in 12 normal adults, and of supplementing the diet with a fair quantity of low-oxalate fruits and vegetables in 26 idiopathic calcium stone formers characterized by hypocitraturia and a very low fruit and vegetable intake in their usual diet.ResultsIn the normal subjects, the elimination of fruits and vegetables from the diet decreased the urinary excretion of potassium (-62%), magnesium (-26%), citrate (-44%) and oxalate (-31%), and increased that of calcium (+49%) and ammonium (+12%) (P < 0.05 for all). The relative saturation for calcium oxalate and calcium phosphate increased from 6.33 to 8.24 (P = 0.028), and from 0.68 to 1.58 (P = 0.050), respectively.In the hypocitraturic stone formers, the introduction of these foods in the diet increased urinary volume (+64%), pH (from 5.84 to 6.19), excretion of potassium (+68%), magnesium (+23%), and citrate (+68%), while it decreased the excretion of ammonium (-18%) (P < 0.05 for all). The relative saturation for calcium oxalate and uric acid fell from 10.17 to 4.96 (P < 0.001), and from 2.78 to 1.12 (P = 0.003), respectively.ConclusionThe total elimination of fruits and vegetables in normal subjects brings about adverse changes in the urinary stone risk profile that are only partially counterbalanced by a reduction in oxalate. In contrast, the addition of these foods to the diet of hypocitraturic stone formers not used to eating them not only significantly increases citrate excretion without affecting oxalate excretion, but also decreases calcium oxalate and uric acid relative saturation

A canonical correlation analysis of the association between carcass and ham traits in pigs used to produce dry-cured ham

The association between carcass and ham traits in a pig population used to produce dry-cured ham was studied using canonical correlation analysis. The carcass traits examined were hot carcass weight (HCW), backfat thickness (BT) and loin depth (LD), and the ham traits studied were gross ham weight (GHW), trimmed ham weight (THW), ham inner layer fat thickness (HIFT), ham outer layer fat thickness (HOFT), pH (pH) and the Göfo value. Carcass and ham traits are not independent. The canonical correlations (r) between the carcass and ham traits at 130 kg were 0.77, 0.24 and 0.20 for the first, second and third canonical pair, respectively, and were all significant (p < 0.01) by the Wilks test. The corresponding canonical correlations between the three canonical variate pairs for the carcass and ham traits at 160 kg were 0.88, 0.42 and 0.14, respectively (p < 0.05 for all, except the third). The correlations between the traits and their canonical variate showed an association among HCW, GHW and THW, and between BT and HOFT. These results indicate that carcass traits should be used to cull pigs that are not suitable for dry-cured ham production

Persistent or Transient Human β Cell Dysfunction Induced by Metabolic Stress: Specific Signatures and Shared Gene Expression with Type 2 Diabetes

Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying β cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human β cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved β cell-targeted therapeutic strategies

Avós e netos na literatura infantil: vidas compartilhadas

Este estudo aborda a representação de personagens velhas na literatura infantil do século XXI, com o foco na convivência entre avós e netos que, apesar das diferenças etárias, conseguem construir relações igualitárias. Para tanto, investiga em que medida as narrativas selecionadas recuperam as vozes, as histórias e os ensinamentos das personagens idosas, observando se as experiências desses sujeitos são valorizadas. Ao resgatar a função social do idoso nas narrativas infantis, por meio das lembranças e histórias contadas, o texto busca revelar as relações igualitárias entre avós e netos sem desconsiderar as diferenças, o que torna possível a coeducação de gerações e o aprendizado com a sabedoria descartada pela modernidade