Explore the vast range of titles available.

The origins of Western culture extensively relate to Ancient Greek culture. While many ancient cultures have contributed to our current knowledge about medicine and the origins of psychiatry, the Ancient Greeks were among the best observers of feelings and moods patients expressed towards medicine and toward what today is referred to as 'psychopathology'. Myths and religious references were used to explain what was otherwise impossible to understand or be easily communicated. Most ancient myths focus on ambiguous feelings patients may have had towards drugs, especially psychotropic ones. Interestingly, such prejudices are common even today. Recalling ancient findings and descriptions made using myths could represent a valuable knowledge base for modern physicians, especially for psychiatrists and their patients, with the aim of better understanding each other and therefore achieving a better clinical outcome. This paper explores many human aspects and feelings towards doctors and their cures, referring to ancient myths and focusing on the perception of mental illness.

This positron emission tomography (PET) study aimed to further define selectivity of [(11)C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [(11)C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [(11)C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [(11)C]Ro15-4513 time-activity curves was used to describe distribution volume (V(T)) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant V(T) decrease (~10%) in [(11)C]flumazenil, but no decrease in [(11)C]Ro15-4513 binding. Further analysis of [(11)C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [(11)C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.This positron emission tomography (PET) study aimed to further define selectivity of [(11)C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [(11)C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [(11)C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [(11)C]Ro15-4513 time-activity curves was used to describe distribution volume (V(T)) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant V(T) decrease (~10%) in [(11)C]flumazenil, but no decrease in [(11)C]Ro15-4513 binding. Further analysis of [(11)C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [(11)C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

This positron emission tomography (PET) study aimed to further define selectivity of [ super(11)C]Ro15-4513 binding to the GABAR alpha 5 relative to the GABAR alpha 1 benzodiazepine receptor subtype. The impact of zolpidem, a GABAR alpha 1-selective agonist, on [ super(11)C]Ro15-4513, which shows selectivity for GABAR alpha 5, and the nonselective benzodiazepine ligand [ super(11)C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [ super(11)C]Ro15-4513 time-activity curves was used to describe distribution volume (V sub(T)) differences in regions populated by different GABA receptor subtypes. Those with low alpha 5 were best fitted by one-tissue compartment models; and those with high alpha 5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant V sub(T) decrease ( similar to 10%) in [ super(11)C]flumazenil, but no decrease in [ super(11)C]Ro15-4513 binding. Further analysis of [ super(11)C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both alpha 1 and alpha 5 subtypes compared with those containing only alpha 1. Zolpidem reduced one component (mean+/-s.d.: 71%+/-41%), presumed to reflect alpha 1-subtype binding, but not another (13%+/-22%), presumed to reflect alpha 5. The proposed method for [ super(11)C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

An Enhanced Recovery After Surgery (ERAS) program in colorectal surgery is able to significantly reduce the morbidity rates and postoperative hospital stay (LOS) related to the intervention. However, it is not clear what modalities and levels of implementation are necessary to achieve these results. The purpose of this work is to analyze the methods and results of the first year of implementation of the program in two centers of the Agenzia Sanitaria Unica Regionale (ASUR) Marche. After a structured implementation pathway, characterized by the creation of a core team, field training, internal courses and coaching, the details of 196 consecutive cases of patients submitted to colorectal resection over a one-year period in two surgical units of the ASUR Marche were prospectively loaded in a database, considering over 50 variables including adherence to the individual items of the ERAS program. The primary outcomes were: overall and major morbidity, mortality and anastomotic dehiscence rates; secondary outcomes were: LOS, re-admission and re-intervention rates. The results of primary endpoints were evaluated by univariable and multivariable analyses with logistic regression and, thereafter, according to ERAS item adherence rate. After a median (interquartile range, IQR) follow-up of 40 (32-94) days, we recorded complications in 72 patients (overall morbidity 36.7%), major morbidity in 14 patients (7.1%), 6 deaths (mortality 3.1%), an anastomotic dehiscence in 9 cases (4.9%), median (IQR) overalll LOS 5 (3-7) days, 10 readmissions (5.1%) and 13 reoperations (6.7%). The mean adherence rate to the items of the ERAS program was 85.4%, showing a significant dose-effect curve for overall morbidity, major morbidity, anastomotic leakage and for overall LOS. The ERAS implementation methods in this project led to a high adherence (>80%) to the program items. All the results showed a significant improvement compared to the previous pre-implementation period and according to the adherence to program items rate.

This positron emission tomography (PET) study aimed to further define selectivity of [(11)C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [(11)C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [(11)C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [(11)C]Ro15-4513 time-activity curves was used to describe distribution volume (V(T)) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that zolpidem caused a significant V(T) decrease (~10%) in [(11)C]flumazenil, but no decrease in [(11)C]Ro15-4513 binding. Further analysis of [(11)C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean±s.d.: 71%±41%), presumed to reflect α1-subtype binding, but not another (13%±22%), presumed to reflect α5. The proposed method for [(11)C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

This positron emission tomography (PET) study aimed to further define selectivity of [11C]Ro15-4513 binding to the GABARα5 relative to the GABARα1 benzodiazepine receptor subtype. The impact of zolpidem, a GABARα1-selective agonist, on [11C]Ro15-4513, which shows selectivity for GABARα5, and the nonselective benzodiazepine ligand [11C]flumazenil binding was assessed in humans. Compartmental modelling of the kinetics of [11C]Ro15-4513 time-activity curves was used to describe distribution volume (VT) differences in regions populated by different GABA receptor subtypes. Those with low α5 were best fitted by one-tissue compartment models; and those with high α5 required a more complex model. The heterogeneity between brain regions suggested spectral analysis as a more appropriate method to quantify binding as it does not a priori specify compartments. Spectral analysis revealed that Zolpidem caused a significant VT decrease (~10%) in [11C]flumazenil, but no decrease in [11C]Ro15-4513 binding. Further analysis of [11C]Ro15-4513 kinetics revealed additional frequency components present in regions containing both α1 and α5 subtypes compared with those containing only α1. Zolpidem reduced one component (mean ± s.d.: 71% ± 41%), presumed to reflect α1-subtype binding, but not another (13% ± 22%), presumed to reflect α5. The proposed method for [11C]Ro15-4513 analysis may allow more accurate selective binding assays and estimation of drug occupancy for other nonselective ligands.

Introduzione. Un programma di Enhanced Recovery After Surgery (ERAS) in chirurgia colorettale è in grado di ridurre significativamente i tassi di morbilità e la durata della degenza postoperatoria (LOS) legati all’intervento. Tuttavia, non è chiaro quali modalità e livelli di implementazione siano necessari per il raggiungimento di tali risultati. Scopo del presente lavoro è quello di analizzare le modalità e i risultati del primo anno di implementazione del programma in due unità operative della Azienda Sanitaria Unica Regionale (ASUR) Marche. Materiali. Dopo un percorso di implementazione strutturato, caratterizzato da formazione di una squadra centrale, formazione sul campo, corsi interni e coaching, 196 casi consecutivi di pazienti sottoposti a resezione colorettale nel corso di un anno in due unità operative della ASUR Marche sono stati inseriti prospetticamente in un database, considerando oltre 50 variabili inclusive della aderenza ai singoli item del programma ERAS. Gli esiti primari sono stati: morbilità globale e maggiore, mortalità, deiscenza anastomotica; gli esiti secondari LOS, re-ricovero e re-intervento. I risultati degli esiti primari sono stati valutati mediante analisi univariate e multivariate con regressione logistica e, quindi, secondo il tasso di aderenza agli item del programma. Risultati. Dopo un follow-up mediano di 40 giorni (range interquartile, IQR 32-94) abbiamo registrato complicanze in 72 pazienti (morbilità globale 36,7%), morbilità maggiore in 14 pazienti (7,1%), 6 decessi (mortalità 3,1%), una deiscenza anastomotica in 9 casi (4,9%), una LOS globale mediana (IQR) pari a 5 (3-7) giorni, 10 re-ricoveri (5,1%) e 13 re-interventi (6,7%). Il tasso medio di aderenza agli item del programma ERAS è risultato pari a 85,4%, mostrando una curva dose-effetto significativa per i tassi di morbilità globale, morbilità maggiore, deiscenza anastomotica e per la LOS globale. Discussione. Le modalità di implementazione di un programma ERAS in chirurgia colorettale nel presente studio hanno condotto a una elevata aderenza (> 80%) agli item del programma. Tutti gli esiti hanno mostrato un significativo miglioramento rispetto allo storico precedente alla implementazione e in relazione al tasso di aderenza agli item del programma.

Objective: Depression and anger have been separately associated with cardiovascular risk factors. We investigated if major depressive disorder (MDD) with concomitant anger attacks was associated with cardiovascular risk factors. Method: We measured total serum cholesterol, glycemia, resting blood pressure, and smoking parameters in 333 (52.9% women) MDD non-psychotic outpatients, mean age of 39.4 years. MDD was diagnosed with the Structured Clinical Interview (SC1D) in accordance with the Diagnostic and Statistic Manual of Mental Disorders, Third Edition, Revised (DSM-III-R). The presence of anger attacks was established with the Massachusetts General Hospital Anger Attacks Questionnaire. Results: In a logistic regression analysis, anger attacks were independently associated with cholesterol levels ≥ 200mg/dL (odds ratio [OR], 2.16; 95% confidence interval [CI], 1.18–3.94) and years of smoking >11 (OR, 2.59; 95%CI, 1.32–5.04). Conclusions: MDD with anger attacks was significantly associated with increased cholesterol levels and years of smoking.

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.Stravalaci et al. examined recognition of SARS-CoV-2 by human soluble innate pattern recognition receptor. They report that pentraxin 3 and mannose-binding protein recognize viral nucleoprotein and spike, respectively. Mannose-binding lectin has antiviral activity, and human genetic polymorphisms of MBL2 are associated with more severe COVID-19.

Duchenne muscular dystrophy (DMD) is a rare genetic disease leading to progressive muscle wasting, respiratory failure, and cardiomyopathy. Although muscle fibrosis represents a DMD hallmark, the organisation of the extracellular matrix and the molecular changes in its turnover are still not fully understood. To define the architectural changes over time in muscle fibrosis, we used an mdx mouse model of DMD and analysed collagen and glycosaminoglycans/proteoglycans content in skeletal muscle sections at different time points during disease progression and in comparison with age-matched controls. Collagen significantly increased particularly in the diaphragm, quadriceps, and gastrocnemius in adult mdx, with fibrosis significantly correlating with muscle degeneration. We also analysed collagen turnover pathways underlying fibrosis development in cultured primary quadriceps-derived fibroblasts. Collagen secretion and matrix metalloproteinases (MMPs) remained unaffected in both young and adult mdx compared to wt fibroblasts, whereas collagen cross-linking and tissue inhibitors of MMP (TIMP) expression significantly increased. We conclude that, in the DMD model we used, fibrosis mostly affects diaphragm and quadriceps with a higher collagen cross-linking and inhibition of MMPs that contribute differently to progressive collagen accumulation during fibrotic remodelling. This study offers a comprehensive histological and molecular characterisation of DMD-associated muscle fibrosis; it may thus provide new targets for tailored therapeutic interventions.