Nuovi motivi azabiciclo [X.2.1] alcanici

Abbiamo intrapreso uno studio accurato avente come oggetto la reazione tra un reagente silossidienico a base pirrolica il N-(terzbutilossicarbonil)- 2-(terz-butildimetilsililossi)pirrolo (TBSOP, 1), e una serie di accettori chetonici di varia natura, simmetrici ed asimmetrici, enolizzabili e non, achirali prochirali e chirali prochirali enantiopur

Sintesi totale di amminoacidi a base ciclitolica: un approccio orientato alla diversità

Amminoacidi carbociclici con funzionalità multiple installate sulle varie posizioni anulari, come le strutture polioliche 1-8 di questo studio, rappresentano un insieme molecolare omogeneo e, allo stesso tempo, variato, in cui ciascuna entità può essere vista sotto diverse angolazioni

Second-generation antipsychotic and diabetes mellitus in children and adolescents

Second generation antipsychotics (SGA) are used in children for the treatment of various psychiatric diseases, including pervasive developmental disorders. These drugs can cause metabolic effects as hyperglycemia and diabetes. A 16-year-old young-boy, diagnosed with autism, developed diabetes mellitus type 1 whilst he was on treatment with olanzapine (started 4 months before), clomipramine, valproic acid and lithium. The hypothesis of druginduced diabetes imposed olanzapine interruption and clozapine initiation. Insulin therapy was practiced, with progressive dosage reduction, until complete cessation of treatment after 13 months. Blood sugar and HbA1c levels remained stable for about a year and then increased again, requiring the introduction of metformin that improved glycemia. In children and adolescents assuming SGA serum glucose and lipid profile should always be assessed before therapy and then frequently monitored. Drug selection must consider family history and the individual risk. Molecule final choice remains equilibrium between efficacy and safety

Sintesi di nuove strutture macrocicliche a ridotta libertà conformazionale

L'obiettivo della nostra ricerca consiste nella creazione di nuove strutture macrocicliche a ridotta libertà conformazionale che incorporino la sequenza consensus RGD per mezzo di una funzione γ-amminoacidica supportata da anelli ciclopentanici (Acpca), ossidrilati e non. Tali scaffold amminoacidici possono essere visti di fatto come mimetici dell’acido γ- amminobutanoico bloccato in una conformazione a W da un ponte α,γ-etilene o idrossietilene. La valutazione biologica in vitro dei ciclo-pseudopeptidi mediante test di binding verso i recettori αvβ3 e αvβ5 isolati, l’approfondito studio strutturale in soluzione via NMR e, infine, studi di docking eseguiti sulla struttura a raggi X del segmento extracellulare dell’integrina αvβ3 complessata con il composto di riferimento EMD121974 hanno completato il nostro studio

Nanoparticle Thin Films for Gas Sensors Prepared by Matrix Assisted Pulsed Laser Evaporation

The matrix assisted pulsed laser evaporation (MAPLE) technique has been used for the deposition of metal dioxide (TiO2, SnO2) nanoparticle thin films for gas sensor applications. For this purpose, colloidal metal dioxide nanoparticles were diluted in volatile solvents, the solution was frozen at the liquid nitrogen temperature and irradiated with a pulsed excimer laser. The dioxide nanoparticles were deposited on Si and Al2O3 substrates. A rather uniform distribution of TiO2 nanoparticles with an average size of about 10 nm and of SnO2 nanoparticles with an average size of about 3 nm was obtained, as demonstrated by high resolution scanning electron microscopy (SEM-FEG) inspections. Gas-sensing devices based on the resistive transduction mechanism were fabricated by depositing the nanoparticle thin films onto suitable rough alumina substrates equipped with interdigitated electrical contacts and heating elements. Electrical characterization measurements were carried out in controlled environment. The results of the gas-sensing tests towards low concentrations of ethanol and acetone vapors are reported. Typical gas sensor parameters (gas responses, response/recovery time, sensitivity, and low detection limit) towards ethanol and acetone are presented

Symptomatic remission and recovery in major psychosis: Is there a role for BDNF? A secondary analysis of the LABSP cohort data

Remission, relapse prevention, and clinical recovery are crucial areas of interest in schizophrenia (SCZ) research. Although SCZ is a chronic disorder with poor overall outcomes, years of research demonstrated that recovery is possible. There are considerable data linking brain-derived neurotrophic factor (BDNF) to SCZ, however, evidence on the role of BDNF in remission in SCZ is scarce. This secondary analysis of the Longitudinal Assessment of BDNF in Sardinian patients (LABSP) data aimed to investigate the relationship between serum BDNF levels and symptomatic remission, simultaneous clinical and functional remission, and recovery in patients with SCZ. A total of 105 patients with SCZ or schizoaffective disorder were recruited for a longitudinal assessment of BDNF levels over 24 months. Longitudinal data were analyzed using mixed-effects linear regression models. The study found significant associations between use of long acting injectables (chi 2 = 7.075, df = 1, p = 0.008), baseline serum BDNF levels (U = 701, z = -2.543, p = 0.011), and "childhood" (U = 475, z = -2.124, p = 0.034) and "general" (U = 55, z = -2.014, p = 0.044) subscales of the Premorbid Adjustment Scale (PAS) with patients maintaining remission and recovery. The diagnosis of SCZ was significantly associated with lower BDNF levels for patients with simultaneous clinical and functional remission (Z = 2.035, p = 0.0419) and recovery (Z = 2.009, p = 0.0445) compared to those without. There were no significant associations between remission in the entire sample and longitudinal serum BDNF levels or genetic variants within the BDNF gene. These findings provide further insight into the complex relationship between BDNF and SCZ

A Secondary Analysis of the Complex Interplay between Psychopathology, Cognitive Functions, Brain Derived Neurotrophic Factor Levels, and Suicide in Psychotic Disorders: Data from a 2-Year Longitudinal Study

Identifying phenotypes at high risk of suicidal behaviour is a relevant objective of clinical and translational research and can facilitate the identification of possible candidate biomarkers. We probed the potential association and eventual stability of neuropsychological profiles and serum BDNF concentrations with lifetime suicide ideation and attempts (LSI and LSA, respectively) in individuals with schizophrenia (SCZ) and schizoaffective disorder (SCA) in a 2-year follow-up study. A secondary analysis was conducted on a convenience sample of previously recruited subjects from a single outpatient clinic. Retrospectively assessed LSI and LSA were recorded by analysing the available longitudinal clinical health records. LSI + LSA subjects consistently exhibited lower PANSS-defined negative symptoms and better performance in the BACS-letter fluency subtask. There was no significant association between BDNF levels and either LSI or LSA. We found a relatively stable pattern of lower negative symptoms over two years among patients with LSI and LSA. No significant difference in serum BDNF concentrations was detected. The translational viability of using neuropsychological profiles as a possible avenue for the identification of populations at risk for suicide behaviours rather than the categorical diagnosis represents a promising option but requires further confirmation

Years of life that could be saved from prevention of hepatocellular carcinoma

BACKGROUND: Hepatocellular carcinoma (HCC) causes premature death and loss of life expectancy worldwide. Its primary and secondary prevention can result in a significant number of years of life saved. AIM: To assess how many years of life are lost after HCC diagnosis. METHODS: Data from 5346 patients with first HCC diagnosis were used to estimate lifespan and number of years of life lost after tumour onset, using a semi-parametric extrapolation having as reference an age-, sex- and year-of-onset-matched population derived from national life tables. RESULTS: Between 1986 and 2014, HCC lead to an average of 11.5 years-of-life lost for each patient. The youngest age-quartile group (18-61 years) had the highest number of years-of-life lost, representing approximately 41% of the overall benefit obtainable from prevention. Advancements in HCC management have progressively reduced the number of years-of-life lost from 12.6 years in 1986-1999, to 10.7 in 2000-2006 and 7.4 years in 2007-2014. Currently, an HCC diagnosis when a single tumour <2 cm results in 3.7 years-of-life lost while the diagnosis when a single tumour 65 2 cm or 2/3 nodules still within the Milan criteria, results in 5.0 years-of-life lost, representing the loss of only approximately 5.5% and 7.2%, respectively, of the entire lifespan from birth. CONCLUSIONS: Hepatocellular carcinoma occurrence results in the loss of a considerable number of years-of-life, especially for younger patients. In recent years, the increased possibility of effectively treating this tumour has improved life expectancy, thus reducing years-of-life lost

Exploring the association between brain-derived neurotrophic factor (BDNF) levels and longitudinal psychopathological and cognitive changes in Sardinian psychotic patients

Background and Hypothesis: Schizophrenia is among the most debilitating mental disorders and has complex pathophysiological underpinnings. There is growing evidence that brain-derived neurotrophic factor (BDNF) can play a role in its pathogenesis. The present study investigated the longitudinal variation of serum BDNF levels in a 24-month observational prospective cohort study of Sardinian psychotic patients and its relationship with psychopathological and cognitive changes. Further, we examined whether genetic variation within the BDNF gene could moderate these relationships. Study design: Every six months 105 patients were assessed for their BDNF serum levels, as well as for a series of psychopathological, cognitive, and social measures. We performed a targeted analysis of four tag single nucleotide polymorphisms (SNPs) within the BDNF gene that were selected and analyzed using Polymerase Chain Reaction (PCR). Longitudinal data were analyzed using mixed-effects linear regression models (MLRM). Study results: We observed a declining longitudinal trajectory of BDNF levels in psychotic patients in general, and in relation to the severity of depressive and negative symptoms. BDNF serum levels also declined in patients scoring lower in cognitive measures such as attention and speed of information processing and verbal fluency. The rs7934165 polymorphism moderated the significant association between verbal fluency and BDNF levels. Conclusions: These findings in patients from real-world settings suggest a plausible role of peripheral BDNF levels as a marker of illness burden in schizophrenia spectrum disorders

Accuracy of self-assessment of real-life functioning in schizophrenia

A consensus has not yet been reached regarding the accuracy of people with schizophrenia in self-reporting their real-life functioning. In a large (n=618) cohort of stable, community-dwelling schizophrenia patients we sought to: (1) examine the concordance of patients' reports of their real-life functioning with the reports of their key caregiver; (2) identify which patient characteristics are associated to the differences between patients and informants. Patient-caregiver concordance of the ratings in three Specific Level of Functioning Scale (SLOF) domains (interpersonal relationships, everyday life skills, work skills) was evaluated with matched-pair t tests, the Lin's concordance correlation, Somers' D, and Bland-Altman plots with limits of agreement (LOA). Predictors of the patient-caregiver differences in SLOF ratings were assessed with a linear regression with multivariable fractional polynomials. Patients' self-evaluation of functioning was higher than caregivers' in all the evaluated domains of the SLOF and 17.6% of the patients exceeded the LOA, thus providing a self-evaluation discordant from their key caregivers. The strongest predictors of patient-caregiver discrepancies were caregivers' ratings in each SLOF domain. In clinically stable outpatients with a moderate degree of functional impairment, self-evaluation with the SLOF scale can become a useful, informative and reliable clinical tool to design a tailored rehabilitation program