Outcome at 2-year of treatment in first-episode psychosis patients who were enrolled in a specialized early intervention program

Treatment in early intervention services (EIS) seems superior to treatment as usual on several outcomes, but the extent of heterogeneity in response is unclear. In this study, treatment response trajectories up to 2 years in first-episode psychosis (FEP) patients enrolled in an Italian early intervention service (EIS) have been quantified. The 24-item Brief Psychiatric Rating Scale (BPRS) was used to quantify treatment response up to 2 years in 129 participants. Conditional growth modeling and latent class growth analysis were used to test changes over time in the BPRS and separation into independent classes over time. Group differences were tested on socio-demographic and clinical variables known to be related to outcome in psychosis. Scores on the BPRS showed a statistically significant decrease in overall scores across all tested models. Four trajectories were identified across 2 years. Most patients showed a progressive decrease in the BPRS scores; a scant fraction showed a more stepped decrease from very high levels of psychopathology. No potential predictor was statistically related to the time course of BPRS scores. Most patients that undergo treatment within an EIS are characterized by amelioration, but patients that have higher baseline scores of psychopathology require more intensive treatment

Protective role of vitamin B6 (PLP) against DNA damage in Drosophila models of type 2 diabetes

Growing evidence shows that improper intake of vitamin B6 increases cancer risk and several studies indicate that diabetic patients have a higher risk of developing tumors. We previously demonstrated that in Drosophila the deficiency of Pyridoxal 5' phosphate (PLP), the active form of vitamin B6, causes chromosome aberrations (CABs), one of cancer prerequisites, and increases hemolymph glucose content. Starting from these data we asked if it was possible to provide a link between the aforementioned studies. Thus, we tested the effect of low PLP levels on DNA integrity in diabetic cells. To this aim we generated two Drosophila models of type 2 diabetes, the first by impairing insulin signaling and the second by rearing flies in high sugar diet. We showed that glucose treatment induced CABs in diabetic individuals but not in controls. More interestingly, PLP deficiency caused high frequencies of CABs in both diabetic models demonstrating that hyperglycemia, combined to reduced PLP level, impairs DNA integrity. PLP-depleted diabetic cells accumulated Advanced Glycation End products (AGEs) that largely contribute to CABs as α-lipoic acid, an AGE inhibitor, rescued not only AGEs but also CABs. These data, extrapolated to humans, indicate that low PLP levels, impacting on DNA integrity, may be considered one of the possible links between diabetes and cancer

Tissue-Specific Differences in Human Transfer RNA Expression

Over 450 transfer RNA (tRNA) genes have been annotated in the human genome. Reliable quantitation of tRNA levels in human samples using microarray methods presents a technical challenge. We have developed a microarray method to quantify tRNAs based on a fluorescent dye-labeling technique. The first-generation tRNA microarray consists of 42 probes for nuclear encoded tRNAs and 21 probes for mitochondrial encoded tRNAs. These probes cover tRNAs for all 20 amino acids and 11 isoacceptor families. Using this array, we report that the amounts of tRNA within the total cellular RNA vary widely among eight different human tissues. The brain expresses higher overall levels of nuclear encoded tRNAs than every tissue examined but one and higher levels of mitochondrial encoded tRNAs than every tissue examined. We found tissue-specific differences in the expression of individual tRNA species, and tRNAs decoding amino acids with similar chemical properties exhibited coordinated expression in distinct tissue types. Relative tRNA abundance exhibits a statistically significant correlation to the codon usage of a collection of highly expressed, tissue-specific genes in a subset of tissues or tRNA isoacceptors. Our findings demonstrate the existence of tissue-specific expression of tRNA species that strongly implicates a role for tRNA heterogeneity in regulating translation and possibly additional processes in vertebrate organisms

Large Scale Comparative Codon-Pair Context Analysis Unveils General Rules that Fine-Tune Evolution of mRNA Primary Structure

BACKGROUND: Codon usage and codon-pair context are important gene primary structure features that influence mRNA decoding fidelity. In order to identify general rules that shape codon-pair context and minimize mRNA decoding error, we have carried out a large scale comparative codon-pair context analysis of 119 fully sequenced genomes. METHODOLOGIES/PRINCIPAL FINDINGS: We have developed mathematical and software tools for large scale comparative codon-pair context analysis. These methodologies unveiled general and species specific codon-pair context rules that govern evolution of mRNAs in the 3 domains of life. We show that evolution of bacterial and archeal mRNA primary structure is mainly dependent on constraints imposed by the translational machinery, while in eukaryotes DNA methylation and tri-nucleotide repeats impose strong biases on codon-pair context. CONCLUSIONS: The data highlight fundamental differences between prokaryotic and eukaryotic mRNA decoding rules, which are partially independent of codon usage

Antidepressant and antipsychotic use in an Italian pediatric population

<p>Abstract</p> <p>Background</p> <p>The safety and effectiveness of psychotropic drug use in the paediatric population is widely debated, in particular because of the lack of data concerning long term effects.</p> <p>In Italy the prevalence of psychotropic drug prescriptions increased in the early 2000s and decreased afterwards. In such a context, a study with the aim to estimate the incidence and prevalence of psychotropic drug prescription in the paediatric population and to describe diagnostic and therapeutic approaches was performed.</p> <p>Methods</p> <p>The study population was composed of 76,000 youths less than 18 years and living in the area covered by the local health unit of Verona, Italy. The data source was the Verona local health unit's administrative prescription database. Prevalence and incidence of antidepressant and/or antipsychotic drug prescriptions in the 2004-2008 period were estimated. Children and adolescents receiving antidepressant and/or antipsychotic drug prescriptions between 1 January 2005 and 31 December 2006 were identified and questionnaires were sent to the prescribers with the aim to collect data concerning diagnostic and therapeutic approaches, and care strategies.</p> <p>Results</p> <p>The prevalence of psychotropic drug prescriptions did not change in the 2004-2008 period, while incidence slightly increased (from 7.0 in 2005 to 8.3 per 10,000 in 2008). Between 1 January 2005 and 31 December 2006, 111 youths received at least one psychotropic drug prescription, 91 of whom received antidepressants. Only 28 patients attended child and adolescent psychiatry services. Information concerning diagnostic and therapeutic approaches, and care strategies was collected for 52 patients (47%). Anxiety-depressive syndrome and attention disorders were the diseases for which psychotropic drugs were most commonly prescribed. In all, 75% youths also received psychological support and 20% were prescribed drugs for 2 or more years.</p> <p>Conclusions</p> <p>Despite the low drug prescription prevalence, the finding that most children were not cared for by child and adolescent psychiatric services is of concern and calls for a systematic, continuous monitoring of psychopharmacological treatments.</p

Anti-asthma medication prescribing to children in the Lombardy Region of Italy: chronic versus new users

<p>Abstract</p> <p>Background</p> <p>Although anti-asthma medications are amongst those most frequently under or over prescribed it is generally accepted that prescriptions for such agents can be used as a proxy for disease prevalence. The aims of this study were to estimate prevalence and incidence of childhood asthma in a representative Italian area by analysing three years of anti-asthmatic prescriptions and hospitalizations of subjects with chronic or first time treatment, and to underline appropriateness of therapeutic choices.</p> <p>Methods</p> <p>The analysis involved prescriptions given to 6-17 year olds between 2003 and 2005 in Italy's Lombardy Region. The youths were classified as potential asthmatics, based on the different degree of drug utilization: occasional, low or high users, and grouped as 'new onset' or 'chronic' cases based on the duration of therapy dispensed. The analysis of prescriptions and hospitalization rate of these groups provided an estimate of the 2005 asthma prevalence and incidence and allowed an estimation of the level of appropriateness of treatments.</p> <p>Results</p> <p>During 2005, the estimated incidence of potential asthmatics was 0.8% and the estimated prevalence was 3.5%. When viewed retrospectively for two years, records showed that 47% of potential asthmatics received prescriptions also during 2004 and 30% also during 2003. During the three years considered, 7.5%, 2.8%, and 1.5% of high, low, and occasional users, respectively, were hospitalized for asthma. The most important inappropriateness found was the prescription of long acting beta adrenergics as first time treatment.</p> <p>Conclusions</p> <p>This study allowed a proxy of asthma incidence, prevalence, and severity. The analyses highlighted a low compliance with the guidelines, suggesting that educational interventions are needed to obtain a more rational management of childhood asthma, especially in subjects starting therapy.</p