5-Hy­droxy-7-phenyl-5-(prop-2-yn-1-yl)-5,6-dihydro-1-benzofuran-2(4H)-one monohydrate

In the title compound, C17H14O3·H2O, the six-membered ring, which adopts a half-chair conformation, makes a dihedral angle of 24.3 (2)° with the phenyl ring. In the crystal, the components are linked by O—H⋯O hydrogen bonds involving the water mol­ecule, and the hy­droxy and carbonyl groups of the organic compound. These inter­actions form a square-like supra­molecular synthon unit which propagates as chains parallel to the crystallographic b axis. A C—H⋯O interaction also occurs

Data regarding the effect of cannabis consumption on liver function in the prospective PAFIP cohort of first episode psychosis

The presented article describes data from secondary analyses, related to the research article entitled ?Cannabis consumption and Non-Alcoholic Fatty Liver Disease. A three years longitudinal study in first episode non-affective psychosis patients? [1]. We present detailed data regarding the socio-demographic and baseline clinical characteristics of a sample of 390 drug-naïve patients with a first episode of non-affective psychosis, and the differences between cannabis users and non-users in those characteristics. Tables also show the results from cross-sectional and longitudinal statistical analyses exploring the relation between cannabis consumption and liver function, after excluding those patients with hazardous alcohol drinking

Cannabis consumption and non-alcoholic fatty liver disease. A three years longitudinal study in first episode non-affective psychosis patients

INTRODUCTION: Increased incidence of obesity and excess weight lead to an increased incidence of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates a protective effect of cannabis consumption on weight gain and related metabolic alterations in psychosis patients. Overall, patients are at greater risk of presenting fatty diseases, such as NAFLD, partly due to lipid and glycemic metabolic disturbances. However, there are no previous studies on the likely effect of cannabis on liver steatosis. We aimed to explore if cannabis consumption had an effect on hepatic steatosis, in a sample of first-episode (FEP) non-affective psychosis. MATERIAL AND METHODS: A total of 390 patients were evaluated at baseline and after 3?years of initiating the antipsychotic treatment. Anthropometric measurements and liver, lipid, and glycemic parameters were obtained at both time points. All but 6.7% of patients were drug-naïve at entry, and they self-reported their cannabis use at both time points. Liver steatosis and fibrosis were evaluated through validated clinical scores (Fatty Liver Index [FLI], Fibrosis-4 [FIB-4], and NAFLD). RESULTS: At 3-year follow-up, cannabis users presented significantly lower FLI scores than non-users (F?=?13.874; p?<?.001). Moreover, cannabis users less frequently met the criteria for liver steatosis than non-users (X2?=?7.97, p?=?.019). Longitudinally, patients maintaining cannabis consumption after 3?years presented the smallest increment in FLI over time, which was significantly smaller than the increment in FLI presented by discontinuers (p?=?.022) and never-users (p?=?.016). No differences were seen in fibrosis scores associated with cannabis. CONCLUSIONS: Cannabis consumption may produce a protective effect against liver steatosis in psychosis, probably through the modulation of antipsychotic-induced weight gain.Funding sources: The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Next-Val 2017 (ref.: NVAL17/24) and Inn-Val 2018 (ref.: INNVAL18/30) IDIVAL grants; Instituto de Salud Carlos III PI020499, PI050427, PI060507; Plan Nacional de Drogas Research Grant 2005-Orden sco/3246/2004; SENY Fundació Research Grant CI 2005–0308007; and Fundación Marqués de Valdecilla API07/011

Pattern of long-Term weight and metabolic changes after a first-episode of psychosis: Results from a 10-years prospective follow-up of the PAFIP cohort

Background: People with psychosis are at higher risk of cardiovascular events, partly explained by a higher predisposition to gain weight. This has been observed in studies on individuals with a first-episode psychosis (FEP) at short and long term (mainly up to 1 year) and transversally at longer term in people with chronic schizophrenia. However, there is scarcity of data regarding longer-term (above 3-year follow-up) weight progression in FEP from longitudinal studies. The aim of this study is to evaluate the longer-term (10 years) progression of weight changes and related metabolic disturbances in people with FEP. Methods: Two hundred and nine people with FEP and 57 healthy participants (controls) were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric, clinical, and sociodemographic data were collected. Results: People with FEP presented a significant and rapid increase in mean body weight during the first year of treatment, followed by less pronounced but sustained weight gain over the study period (?15.2 kg; SD 12.3 kg). This early increment in weight predicted longer-term changes, which were significantly greater than in healthy controls (?2.9 kg; SD 7.3 kg). Weight gain correlated with alterations in lipid and glycemic variables, leading to clinical repercussion such as increments in the rates of obesity and metabolic disturbances. Sex differences were observed, with women presenting higher increments in body mass index than men. Conclusions: This study confirms that the first year after initiating antipsychotic treatment is the critical one for weight gain in psychosis. Besides, it provides evidence that weight gain keep progressing even in the longer term (10 years), causing relevant metabolic disturbances

Understanding sex differences in long-term outcomes after a first episode of psychosis

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions

Microenvironment Eradication of Hepatitis C: A Novel Treatment Paradigm

OBJECTIVES: Prisons are major reservoirs of hepatitis C virus (HCV) in which a therapeutic approach has been particularly difficult so far. Our aim was to create a permanent program of HCV elimination in a prison based on a "test and treat" strategy. METHODS: This open-label clinical trial was conducted in the Spanish prison "El Dueso" between May 2016 and July 2017. Viremic patients were treated with a ledipasvir-sofosbuvir regimen (8-12 weeks) according to the 2015 Spanish Guidelines. A teleconsultation program was established to follow-up patients from the hospital. Non-responders were submitted for a phylogenetic analysis and offered retreatment. An evaluation of new cases of HCV infection was performed every 6 months and upon release in all inmates. RESULTS: 847 (99.5%) inmates accepted to participate. HCV antibodies were present in 110 (13.0%) and 86 (10.2%) had detectable viremia. Most of them were genotype 1 or 3 (82.6%) and had <F2 fibrosis (52.2%). Treatment was started in the 69 inmates whose stay in prison was longer than 30 days. Sustained virological response was achieved in 64 out of 66 patients (96.9%), three of whom were successfully rescued with a salvage regimen after treatment failure. Two patients were lost to follow-up and three are currently on treatment without viremia. As a result, by July 2017 none of the 409 imprisoned was viremic, and neither reinfections nor de novo infections were detected. CONCLUSIONS: A sustained "test-and-treat" strategy against HCV in prisons is feasible and beneficial. Spreading this strategy should entail a public health impact.Supported by Plan Nacional de I+D+i 2013–2016 and Instituto de Salud Carlos III, Ministerio de Economía, Industria y Competitividad, cofinanced by European Development Regional Fund “A way to achieve Europe”,Operative program Intelligent Growth 2014–2020 and grant PIE15/00079. This study received funding assistance from Gilead Sciences, Spain (IN-ES-337-2089), C/Vía de los Poblados, 3, 28033 Madrid, Spain, http://www.gilead. com/about/worldwide-operations/europe/spain; phone number: +34 913789830), who played no part in study design, data analysis, or in the preparation of the manuscript. All study investigators declare to be independent from funders

A Stereoconvergent Cyclopropanation Reaction of Styrenes

The first stereoconvergent cyclopropanation reaction by means of photoredox catalysis using diiodomethane as methylene source is described. This transformation exhibits broad functional group tolerance and it is characterized by an excellent stereocontrol en route to trans-cyclopropanes regardless of whether E- or Z-styrene substrates were utilized

Enantioselective multicomponent synthesis of fused 6-5 bicyclic 2-butenolides by a cascade heterobicyclisation process

The successive coupling of an alkoxy(aryl/heteroaryl)carbene complex of chromium with either a ketone or an imide lithium enolate and then a 3-substituted (H, TMS, PhCH(2), PhCH(2)CH(2), Me) propargylic organomagnesium reagent has afforded novel hydroxy-substituted bicyclic [4.3.0]-γ-alkylidene-2-butenolides with three modular points that has allowed the efficient introduction of molecular complexity, including a homopropargylic alcohol core. The selective formation of these five- or six-component heterobicyclisation products is the result of the regioselective integration of the Grignard reagent as a propargyl fragment followed by a cascade CO/alkyne/CO insertion, ketene trapping and elimination sequence. By using lithium enolates of chiral N-acetyl-2-oxazolidinones and the corresponding propargylic organocerium reagents, both enantiomers of these bicyclic heterocycles were efficiently prepared with very high enantiomeric purity. Architecturally, these fused bicyclic butenolides are characterised by a highly unsaturated and oxygenated core and they exhibit strong blue fluorescence in solution.Funded by: Ministerio de Ciencia e Innovación of Spain. Grant Numbers: CTQ2007-61048/BQU, CTQ2010-16790 and MEC.Peer Reviewe

(1RS,2RS,3RS)-1,2-Dimethoxy-3-methyl-2-phenyl-1-(2-thienyl)cyclopropane

In the title compound, C16H18O2S, a new cis-1,2-dimethoxycyclopropane, the two methoxy groups are in a cis configuration and in trans positions with respect to the H atom and the phenyl and thienyl rings on the cyclopropyl group. The molecular packing is dominated by weak intermolecular C&amp;#8212;H...O interactions, allowing the formation of zigzag chains propagating parallel to the c axis. The dihedral angle between the aromatic rings is 86.12&amp;#8197;(8)&amp;#176;