Il fenomeno delle dipendenze patologiche nella Provincia di Ragusa. Anno 2005. I Rapporto

Report on the state of legal and illegal substances use in the territory of Ragusa ProvinceIl Report analizza il fenomeno delle dipendenze nel territorio della Provincia di Ragusa. La descrizione del fenomeno si sviluppa intorno all\u27analisi degli indicatori individuati dall\u27Osservatorio Europeo delle Dipendenze di Lisbona (OEDT): 1-uso di sostanze nella popolazione generale (questo indicatore va a rilevare i comportamenti nei confronti di alcol e sostanze psicoattive da parte della popolazione generale); 2-prevalenza d\u27uso problematico delle sostanze psicoattive; 3-domanda di trattamento degli utilizzatori di sostanze; 4-mortalit? degli utilizzatori di sostanze; 5-malattie infettive. Altri due importanti indicatori che si stanno sviluppando, e che vengono qui illustrati, sono l\u27analisi delle Schede di Dimissione Ospedaliera (SDO) e gli indicatori relativi alle conseguenza sociali dell\u27uso di droghe (criminalit? droga correlata). Inoltre sono state applicate diverse metodologie standard di stima sia per quantificare la quota parte sconosciuta di utilizzatori di sostanze che non afferiscono ai servizi, sia per identificarne alcune caratteristiche

Poly (ADP-ribose) polymerase 1 expression in fibroblasts of Down syndrome subjects

Abstract Down syndrome (DS) is the most common chromosomal disorder. It is featured by intellectual disability and is caused by trisomy 21. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. Apoptosis is a programmed cell death process under both normal physiological and pathological conditions. Poly (ADP-ribose) polymerase 1 is a mediator of programmed-necrotic cell death and appears to be also involved in the apoptosis. The aim of the present work was to detect the intracellular distribution of PARP-1 protein using immunofluorescence techniques and the expression of PARP-1 mRNA in culture of fibroblasts of DS subjects. The analysis of the intracellular distribution of PARP-1 show a signal at the nuclear level in about 75 % of the cells of DS subjects with a slight uniformly fluorescent cytoplasm. In contrast, in about 65% of the analyzed fibroblasts of the normal subjects only a slight fluorescent was found. These observations have been confirmed by PARP-1 gene mRNA expression evaluation. The data obtained from this study strengthen the hypothesis that the over-expression of PARP-1 gene could have a role in the activation of the apoptotic pathways acting in the neurodegenerative processes in DS

LDOC1 expression in fibroblasts of patients with Down syndrome

Abstract Down syndrome (DS) is characterised by intellectual disability and is caused by trisomy 21. Apoptosis is a programmed cell death process and is involved in neurodegenerative diseases such as Alzheimer. People with DS can develop some traits of Alzheimer disease at an earlier age than subjects without trisomy 21. The leucine zipper, down regulated in cancer 1 (LDOC1) appears to be involved in the apoptotic pathways. The aim of the present work was to detect the presence of intracellular synthesis of LDOC1 protein and LDOC1 mRNA in fibroblast cultures from DS subjects. The western blot shows the presence of LDOC1 protein in fibroblasts of DS subjects but no evidence of LDOC1 protein in fibroblasts of normal subjects. LDOC1 gene mRNA expression is increased in fibroblasts from DS subjects compared to fibroblasts from normal subjects. The data obtained from this study strengthen the hypothesis that the over-expression of LDOC1 gene could play a role in determining the phenotype of individuals with DS but does not exclude that this results from apoptotic mechanisms

Low TGF-β1 plasma levels are associated with cognitive decline in Down syndrome

Almost all individuals with Down's syndrome (DS) show the characteristic neuropathological features of Alzheimer's disease (AD) by the age of 40, yet not every individual with DS experiences symptoms of AD later in life. Similar to neurotypical developing subjects, AD in people with DS lasts for a long preclinical phase in which biomarkers follow a predictable order of changes. Hence, a prolonged asymptomatic period precedes the onset of dementia, underscoring the importance of identifying new biomarkers for the early detection and monitoring of cognitive decline in individuals with DS. Blood-based biomarkers may offer an alternative non-invasive strategy for the detection of peripheral biological alterations paralleling nervous system pathology in an early phase of the AD continuum. In the last few years, a strong neurobiological link has been demonstrated between the deficit of transforming growth factor-β1 (TGF-β1) levels, an anti-inflammatory cytokine endowed with neuroprotective activity, and early pro-inflammatory processes in the AD brain. In this clinical prospective observational study, we found significant lower plasma TGF-β1 concentrations at the first neuropsychological evaluation (baseline = T0) both in young adult DS individuals (19-35 years) and older DS subjects without AD (35-60 years) compared to age- and sex-matched healthy controls. Interestingly, we found that the lower TGF-β1 plasma concentrations at T0 were strongly correlated with the following cognitive decline at 12 months. In addition, in young individuals with DS, we found, for the first time, a negative correlation between low TGF-β1 concentrations and high TNF-α plasma concentrations, a pro-inflammatory cytokine that is known to be associated with cognitive impairment in DS individuals with AD. Finally, adopting an ex vivo approach, we found that TGF-β1 concentrations were reduced in parallel both in the plasma and in the peripheral blood mononuclear cells (PBMCs) of DS subjects, and interestingly, therapeutic concentrations of fluoxetine (FLX) applied to cultured PBMCs (1 µM for 24 h) were able to rescue TGF-β1 concentrations in the culture media from DS PBMCs, suggesting that FLX, a selective serotonin reuptake inhibitor (SSRI) endowed with neuroprotective activity, might rescue TGF-β1 concentrations in DS subjects at higher risk to develop cognitive decline.The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This project has been funded by the Italian Ministry of Health, grant no: GR-2019-12369983-Theory-enhancing and partially supported with funds by project no. 3 of Ricerca Corrente 2022-2024-Linea 4 of Oasi Research Institute-IRCCS, Troina, Italy, and by FONDO DI ATENEO PER LA RICERCA ANNO 2020, Department of Life Sciences, UNIMORE. FC’s Lab at the Oasi Research Institute is also supported by the European Union’s Horizon 2020 research and innovation program under the grant agreement no. 899986 (ICOD)

A Subset of Patients With Autism Spectrum Disorders Show a Distinctive Metabolic Profile by Dried Blood Spot Analyses

Autism spectrum disorder (ASD) is currently diagnosed according to behavioral criteria. Biomarkers that identify children with ASD could lead to more accurate and early diagnosis. ASD is a complex disorder with multifactorial and heterogeneous etiology supporting recognition of biomarkers that identify patient subsets. We investigated an easily testable blood metabolic profile associated with ASD diagnosis using high throughput analyses of samples extracted from dried blood spots (DBS). A targeted panel of 45 ASD analytes including acyl-carnitines and amino acids extracted from DBS was examined in 83 children with ASD (60 males; age 6.06 ± 3.58, range: 2–10 years) and 79 matched, neurotypical (NT) control children (57 males; age 6.8 ± 4.11 years, range 2.5–11 years). Based on their chronological ages, participants were divided in two groups: younger or older than 5 years. Two-sided T-tests were used to identify significant differences in measured metabolite levels between groups. Näive Bayes algorithm trained on the identified metabolites was used to profile children with ASD vs. NT controls. Of the 45 analyzed metabolites, nine (20%) were significantly increased in ASD patients including the amino acid citrulline and acyl-carnitines C2, C4DC/C5OH, C10, C12, C14:2, C16, C16:1, C18:1 (P: < 0.001). Näive Bayes algorithm using acyl-carnitine metabolites which were identified as significantly abnormal showed the highest performances for classifying ASD in children younger than 5 years (n: 42; mean age 3.26 ± 0.89) with 72.3% sensitivity (95% CI: 71.3;73.9), 72.1% specificity (95% CI: 71.2;72.9) and a diagnostic odds ratio 11.25 (95% CI: 9.47;17.7). Re-test analyses as a measure of validity showed an accuracy of 73% in children with ASD aged ≤ 5 years. This easily testable, non-invasive profile in DBS may support recognition of metabolic ASD individuals aged ≤ 5 years and represents a potential complementary tool to improve diagnosis at earlier stages of ASD development

The effect of autistic traits on disembedding and mental rotation in neurotypical women and men

Funder: Autism Research TrustFunder: Templeton World Charitable FundFunder: NIHR Cambridge Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100018956Funder: National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health ResearchFunder: Care East of England at Cambridgeshire and Peterborough NHS Foundation TrustAbstractRecent data has revealed dissociations between social and non-social skills in both autistic and neurotypical populations. In the present study, we investigated whether specific visuospatial abilities, such as figure disembedding and mental rotation, are differently related to social and non-social autistic traits, in neurotypical women and men. University students (N = 426) completed the Autism Spectrum Quotient (AQ), figure disembedding and mental rotation of two-dimensional figures tasks. AQ social skills (AQ-social) and attention-to-details (AQ-attention) subscales were used as measures of social and non-social autistic traits, respectively. Mental rotation was affected by a significant interaction between sex, social and non-social traits. When non-social traits were above the mean (+ 1 SD), no sex differences in mental rotation were found. Instead, below this value, sex differences depended on the social traits, with men on average outperforming women at middle-to-high social traits, and with a comparable performance, and with women on average outperforming men, at lower social traits. A small positive correlation between figure disembedding and social traits was observed in the overall sample. These results are interpreted in terms of the hyper-systemizing theory of autism and contribute to the evidence of individual differences in the cognitive style of autistic people and neurotypical people with autistic traits.</jats:p

The effect of autistic traits on disembedding and mental rotation in neurotypical women and men

Funder: Autism Research TrustFunder: Templeton World Charitable FundFunder: NIHR Cambridge Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100018956Funder: National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health ResearchFunder: Care East of England at Cambridgeshire and Peterborough NHS Foundation TrustAbstractRecent data has revealed dissociations between social and non-social skills in both autistic and neurotypical populations. In the present study, we investigated whether specific visuospatial abilities, such as figure disembedding and mental rotation, are differently related to social and non-social autistic traits, in neurotypical women and men. University students (N = 426) completed the Autism Spectrum Quotient (AQ), figure disembedding and mental rotation of two-dimensional figures tasks. AQ social skills (AQ-social) and attention-to-details (AQ-attention) subscales were used as measures of social and non-social autistic traits, respectively. Mental rotation was affected by a significant interaction between sex, social and non-social traits. When non-social traits were above the mean (+ 1 SD), no sex differences in mental rotation were found. Instead, below this value, sex differences depended on the social traits, with men on average outperforming women at middle-to-high social traits, and with a comparable performance, and with women on average outperforming men, at lower social traits. A small positive correlation between figure disembedding and social traits was observed in the overall sample. These results are interpreted in terms of the hyper-systemizing theory of autism and contribute to the evidence of individual differences in the cognitive style of autistic people and neurotypical people with autistic traits.</jats:p

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study

: The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p &lt; 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990)

Demographic and clinical determinants of neck pain in idiopathic cervical dystonia.

Cervical dystonia is associated with neck pain in a significant proportion of cases, but the mechanisms underlying pain are largely unknown. In this exploratory study, we compared demographic and clinical variables in cervical dystonia patients with and without neck pain from the Italian Dystonia Registry. Univariable and multivariable logistic regression analysis indicated a higher frequency of sensory trick and a lower educational level among patients with pain