Why lithium should be used in patients with bipolar disorder? A scoping review and an expert opinion paper

Introduction: Lithium treatment is considered the gold standard for the long-term management of bipolar disorder and recurrent unipolar depression. It is also extremely effective in other psychiatric conditions characterized by impulsivity and aggression, and for the prevention of suicidal behaviours. Areas covered: This paper provides a scoping review and an expert commentary regarding the use of lithium in adult patients. Available information about efficacy, tolerability, dosing, and switching is analyzed, and the strategies that may be most useful in real-world clinical settings are highlighted. Expert opinion: Lithium is effective on different domains of bipolar disorder, including the long-term prevention of recurrences of affective episodes, management of acute mania as well as in the prophylaxis of all affective episodes. Lithium has been defined a 'forgotten drug,' since its use in routine clinical practice has been declined over the last 20 or 30 years. Reasons for this trend include lack of adequate training on the management of lithium side effects. Considering its efficacy, use of lithium in ordinary clinical practice should be promoted. Several strategies, such as using slow-release formulations, can be easily implemented in order to minimize lithium side effects and improve its tolerability profile

Quality of life in patients with advanced ovarian cancer after primary debulking surgery versus neoadjuvant chemotherapy: Results from the randomised SCORPION trial (NCT01461850)

Objective To investigate the effect of treatment with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), versus primary debulking surgery (PDS), on quality of life (QoL) in patients with advanced epithelial ovarian cancer (EOC).Design Randomised trial conducted in a single institution.Setting Division of Gynaecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.Sample Patients with stage-IIIC/IV EOC and high tumour load.Methods Patients were randomised (1:1) to undergo either PDS (PDS group) or NACT followed by IDS (NACT/IDS group).Main outcome measures Quality-of-life (QoL) data, assessed using the European Organization for Research and Treatment of Cancer core QoL questionnaire (QLQ-C30) and ovarian cancer module (OV28); co-primary outcomes were the QLQ-C30 global health score at 12 months (cross-sectional analysis) and the difference in mean QLQ-C30 global health score over time between treatment groups (longitudinal analysis).Results From October 2011 to May 2016, 171 patients were enrolled (PDS = 84; NACT/IDS = 87). We observed no clinical or statistically significant difference between treatment groups in any of the QoL functioning scales at 12 months, including QLQ-C30 global health score (NACT/IDS group vs PDS group, mean difference 4.7, 95% CI -4.99 to 14.4, p = 0.340). Over time, we found lower global health scores for those undergoing PDS than for those receiving NACT (difference in mean score 6.27, 95% CI 0.440-12.11, p = 0.035), albeit this was not clinically relevant.Conclusions We found no difference in global QoL related to treatment approach at 12 months, even though patients in the NACT/IDS group reported better global health scores across the 12-month period compared with the PDS group; these findings further confirm that NACT/IDS might be a feasible option for patients unsuitable for PDS

A Design-Oriented Specification Language for defining software requirements

The most common difficulty of requirements elicitation is to define all components and aspects of a project by using the natural language without ambiguities, weak phrases and useless descriptions which make project outlines chaotic. In this paper, we present the Design Oriented Specification Language (DOSLang) that aims at reducing the gap existing among the project stakeholders, which are involved into the requirements specification and comprehension activities. The DOSLang language provides a free-form syntax with the introduction of constructs helping project stakeholders to reducing the ambiguity during definitions, descriptions, todos, actions, constraints and all the other aspects related to requirement definition, without sacrificing the ability of specifying loops and conditional constructs, small sets of data type and multiplicity between 'entities'. The DOSLang compiler is designed to be able to create a common baseline, which the project stakeholders can use during the first phases of the project elicitation. DOSLang is suitable for any kind of project that requires a precise description of all of its aspects. Moreover the language was created keeping the possibility to be used by all people working in a project development: from business people to programmers, including customers

Evaluation of Ki-67 expression in feline non-ocular melanocytic tumours

Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P  5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. Conclusions Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker

Evidence that tirzepatide protects against diabetes-related cardiac damages

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods: A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results: Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. Conclusion: Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT

Loco-regional treatment with temozolomide-loaded thermogels prevents glioblastoma recurrences in orthotopic human xenograft models

Glioblastoma multiforme (GBM) is the most aggressive primary tumor of the central nervous system and the diagnosis is often dismal. GBM pharmacological treatment is strongly limited by its intracranial location beyond the blood–brain barrier (BBB). While Temozolomide (TMZ) exhibits the best clinical performance, still less than 20% crosses the BBB, therefore requiring administration of very high doses with resulting unnecessary systemic side efects. Here, we aimed at designing new negative temperature‐responsive gel formulations able to locally release TMZ beyond the BBB. The biocompatibility of a chitosan‐β‐glycerophosphate‐based thermogel (THG)‐containing mesoporous SiO2 nanoparticles (THG@SiO2) or polycaprolactone microparticles (THG@PCL) was ascertained in vitro and in vivo by cell counting and histological examination. Next, we loaded TMZ into such matrices (THG@SiO2‐TMZ and THG@PCL‐TMZ) and tested their therapeutic potential both in vitro and in vivo, in a glioblastoma resection and recurrence mouse model based on orthotopic growth of human cancer cells. The two newly designed anticancer formulations, consisting in TMZ‐silica (SiO2@TMZ) dispersed in the thermogel matrix (THG@SiO2‐TMZ) and TMZ, spray‐dried on PLC and incorporated into the thermogel (THG@PCL‐TMZ), induced cell death in vitro. When applied intracranially to a resected U87‐MG‐Red‐FLuc human GBM model, THG@SiO2‐TMZ and THG@PCL‐ TMZ caused a signifcant reduction in the growth of tumor recurrences, when compared to untreated controls. THG@SiO2‐TMZ and THG@PCL‐TMZ are therefore new promising gel‐based local therapy candidates for the treatment of GBM

Peripheral Amino Acid Levels in Schizophrenia and Antipsychotic Treatment

Abnormal levels of amino acids have been reported in patients with schizophrenia and have also been investigated as a biomarker to monitor antipsychotic treatment, however results have been inconsistent. The purpose of the present review is to summarize the evidence in the literature of whether amino acid levels can be a biomarker and predict the treatment outcome in schizophrenia. The current review does not support amino acid concentration as a useful biomarker for monitoring antipsychotic response in patients with schizophrenia, although there is evidence that high levels of serum homocysteine and glutamate might be considered as a trait marker for schizophrenia. This review has also highlighted a considerable dearth of studies, specifically of studies evaluating antipsychotic side-effects

Salerno Quadrante. N.1-3 (1955)

1 (giugno 1955): Guglielmo Longo, Ospedali, esigenza prima del Mezzo giorno, P. 3 ; Giuseppe Lanocita, Attualità della questione demaniale e suoi aspetti nel comune di Eboli, P. 9 ; Bilancio di un disastro: L'alluvione in cifre, P. 11 ; Alessandro Pinto, Canti popolari cilentani, P. 17 ; Giovanni Capasso, Poesie inedite, P. 18 ; Francesco Franco. S. Pietro al Tanagro, il paese dalle tovaglie di terra, P. 19 ; Antonio De Angelis, Scafati, cittadina di provincia, P. 23 ; Enzo Barba, Matteo Luciani, P. 25 ; Augusto Visconti, Curiosità e irrequietezza in tre giovani pittori salernitani: D'Agosto, Gentile, Della Monica, P. 28 ; II Centro di cultura Citta di Salerno, P. 29 ; Recensioni, P. 32- 40 ; La resistenza salernitana (fuori testo).2-3 (dicembre 1955): Ugo Renna, Viaggio nel Cilento, P. 3 ; Francesco Franco, La crisi tessile e Ie M.C.M. Fratte-Pellezzano, P. 14 ; Giuseppe Tortorella, II problema del Porto (intervista), P. 23 ; Guglielmo Longo, Difendiamo l'industria salernitana, P. 27 ; Enzo Barba, Errico de Marinis e il "socialismo demariniano, P. 33 ; Giuseppe Lanocita, Attualità della questione demaniale e suoi aspetti nel comune di Eboli, P. 43 ; Giuseppe A. Leone, Pietà per Crocco il brigante (poesia), p. 52 ; Gianni Nunziante, Titoli di proprietà immobiliare al portatore nella pratica medievale salernitana, P. 53 ; Mario Carotenuto, Olga Napoli nella pittura contemporanea (fuori testo)