Lamotrigine Augmentation of Serotonin Reuptake Inhibitors in Severe and Long-Term Treatment-Resistant Obsessive-Compulsive Disorder

The treatment recommendations in obsessive-compulsive disorder (OCD) after lack of response to selective serotonin reuptake inhibitors (SSRIs) include augmentation with other drugs, particularly clomipramine, a more potent serotonin reuptake inhibitor (SRI), or antipsychotics. We present two cases of response to lamotrigine augmentation in treatment-refractory OCD; each received multiple SRI trials over a \u3e10-year period. The first patient had eleven years of treatment with multiple combinations including clomipramine and SSRIs. She had a \u3e50% decrease of Y-BOCS (from 29 to 14) by augmenting paroxetine (60 mg/day) with lamotrigine (100 mg/day). The second patient had 22 years of treatment with multiple combinations, including combinations of SSRIs with clomipramine and risperidone. She had an almost 50% decrease of Y-BOCS (from 30 to 16) and disappearance of tics by augmenting clomipramine (225 mg/d) with lamotrigine (200 mg/day). These two patients were characterized by lack of response to multiple treatments, making a placebo response to lamotrigine augmentation unlikely. Prospective randomized trials in treatment-resistant OCD patients who do not respond to combinations of SSRIs with clomipramine and/or antipsychotics are needed, including augmentation with lamotrigine. Until these trials are available, our cases suggest that clinicians may consider lamotrigine augmentation in such treatment-resistant OCD patients

Registro de nuevo huésped intermediario de Hymenolepis diminuta (Cestoda) en el Perú

Tribolium castaneum (Herbst) is reported as new intermediate host of Hymenolepis diminuta from Peru.Tribolium castaneum (Herbst) es reportado como un nuevo hospedero intermediario de Hymenolepis diminuta en el Perú

First-time admissions for opioid treatment: crosssectional and descriptive study of new opioid users seeking treatment

Background: The purpose of this study was to gain an understanding of the profiles of the new treatment demands posed by opioid addicts between 2005 and 2010 at the addictive disorders assistance units in Galicia, Spain. Methods: A cluster analysis was performed using data from 1,655 treatment entrants. Clusters were constructed using sociodemographic and medicolegal variables. A cluster analysis was also conducted according to age. Once clusters were defined, their association with the following variables was analyzed: age at first use of opioids, years of use, frequency of opioid use in the previous month, psychiatric treatment, cocaine use, existence of a drug-dependent partner, and source of referral. Results: Four clusters were obtained in the main analysis. Cluster 1 (34.01%) consisted of young males, cluster 2 (16.19%) consisted of not-so-young males, cluster 3 (32.62%) consisted mainly of older males and a small group of females, and cluster 4 (17.18%) was made up entirely of women. With regard to age-related clusters, two clusters were obtained in those under the age of 30 years: cluster 1 (73%) without medicolegal complications and cluster 2 (27%) with medicolegal complications. For those over the age of 30 years, two clusters were obtained: cluster 1 (53.92%) with hardly any medicolegal complications and cluster 2 (46.08%) with medicolegal complications. Conclusion: Cluster analysis suggests that there have been no substantial changes in variables indicating greater severity in this new group of patients. Women are likely to seek help earlier, which reduces their duration of opioid use. The younger the patient, the shorter the duration of opioid use and the greater the likelihood of cessation of intravenous use. Public health systems should use a two-pronged treatment strategy of short but intense cessation therapies for women and younger treatment entrants and longer maintenance and replacement therapies for older treatment entrants with more psychosocial and medical complications.This study was partly supported by the Instituto de Salud Carlos III, Centro de Investigacion Biomedica en Red de Salud MentalS

Norovirus GII.3[P12] Outbreak Associated with the Drinking Water Supply in a Rural Area in Galicia, Spain, 2021

On 30 September 2021, the city council of Muxia, Spain (population of 4,564 inhabitants), reported an unusual increase of patients with acute gastroenteritis (AGE). Because geographically widespread villages belonging to the same water supply were affected, a waterborne outbreak was suspected. Overall, 115 probable cases were ascertained during epidemiological investigations carried out by the local health authority (attack rate, 5.7%); the age range was 0 to 92 years, and 54% were female. The main symptoms were vomiting (78.1%) and diarrhea (67.5%). Primary cases peaked on 29 September and subsided on 1 October, compatible with a point-source outbreak followed by possible secondary cases until 7 October. We conducted an unmatched case-control study using phone surveys. The case-control study included 62 cases and 46 controls. Univariate analysis showed that cases had a higher exposure to tap water through direct consumption (odds ratio [OR] = 86; 95% confidence interval [CI], 18 to 409) or vegetable washing (OR = 27; 95% CI, 7 to 98). Norovirus GII was detected in two terminal points of the water supply system, and 14 cases were laboratory confirmed after detection of GII in stool samples. A unique genotype (GII.3[P12]) was identified in stool samples. On 1 October, a tap water ban was put in place and the water was purged and chlorinated. The rapid increase in the number of cases and its decline after implementing control measures suggested a waterborne point-source outbreak among the residents of Muxia sharing the same water distribution system. IMPORTANCE: Noroviruses are likely to be underrecognized in most suspected waterborne outbreaks. Therefore, effective norovirus detection and the early recognition of water as a possible source of infection are important to reduce morbidity as appropriate steps are taken to control the source. In our study, we combined epidemiological, environmental, and microbiological investigations to demonstrate that it was a waterborne outbreak caused by norovirus. Metagenomic sequencing in one norovirus-positive stool sample confirmed norovirus etiology and the absence of other potential pathogens. Detection of fecal indicator bacteria and the fact that the drinking water was not chlorinated suggest a breakdown in chlorination as the cause of the outbreak. This outbreak investigation also demonstrated the importance of timely communication to the public about the risk linked to tap water consumption.This study was partially funded through the project PI20CIII/00005.S

Identification of putative second genetic hits in schizophrenia carriers of high-risk copy number variants and resequencing in additional samples

Copy number variants (CNVs) conferring risk of schizophrenia present incomplete penetrance, suggesting the existence of second genetic hits. Identification of second hits may help to find genes with rare variants of susceptibility to schizophrenia. The aim of this work was to search for second hits of moderate/high risk in schizophrenia carriers of risk CNVs and resequencing of the relevant genes in additional samples. To this end, ten patients with risk CNVs at cytobands 15q11.2, 15q11.2-13.1, 16p11.2, or 16p13.11, were subjected to whole-exome sequencing. Rare single nucleotide variants, defined as those absent from main public databases, were classified according to bioinformatic prediction of pathogenicity by CADD scores. The average number of rare predicted pathogenic variants per sample was 13.6 (SD 2.01). Two genes, BFAR and SYNJ1, presented rare predicted pathogenic variants in more than one sample. Follow-up resequencing of these genes in 432 additional cases and 432 controls identified a significant excess of rare predicted pathogenic variants in case samples at SYNJ1. Taking into account its function in clathrin-mediated synaptic vesicle endocytosis at presynaptic terminals, our results suggest an impairment of this process in schizophrenia

Cognitive-behavioral intervention via interactive multimedia online video game for active aging: study protocol for a randomized controlled trial

Background Due to the progressive aging of the population, programs to promote active aging have been recommended. However, older adults have difficulty accessing them. Interventions administered through online video games may increase their accessibility, and complementing these with a smartphone app will likely increase adherence and allow for ongoing professional monitoring. The objective of this study is to evaluate the efficacy of a cognitive-behavioral intervention for active aging administered through an online interactive multimedia video game that includes a smartphone app companion. The secondary objectives are to analyze the moderators and mediators of the change in the outcome variables and to evaluate the adherence to the intervention. Methods/design A randomized controlled clinical trial will be conducted. Adults 45 years and older will be randomly assigned to a cognitive-behavioral intervention administered through an online multimedia video game that includes a smartphone app companion or to a control group that will receive online information on active aging (274 participants per group). The intervention will be administered in eight weekly 45-min modules. An investigator-blinded evaluation will be conducted using online self-administered tests at baseline, post-intervention, and 6- and 12-month follow-ups. The primary outcome will be mental health status as evaluated using the 36-item Short-Form Health Survey (SF-36) at post-intervention. Secondary outcomes will be emotional well-being, depressive symptoms, reinforcement, negative thoughts, self-reported memory, cognitive task performance, sleep hygiene behaviors, physical activity, eating habits, body mass index, social support, dropout, treatment adherence, and satisfaction with the intervention. Discussion If the results are favorable, this study would involve the development of the first evidence-based active aging promotion intervention based on a video game that includes a smartphone app companion, providing evidence on its efficacy, accessibility, and clinical utility.The development of this protocol was funded by grant EXP - 00091195/ ITC20161137 from Center for Industrial Technological Development of Spain and the European Regional Development Fund, and grant 2018-PU054 from Department of Culture, Education and University RegulationS

Can we predict psychostimulant use in youths? A study with structural equation modeling analysis

Conocer qué factores predicen el consumo de psicoestimulantes en jóvenes es importante para el diseño de programas preventivos y para identificar a los jóvenes que tienen una mayor probabilidad de consumir y así evitar que aparezcan los problemas derivados de dicho consumo. El objetivo de este estudio fue analizar la relación entre la disponibilidad percibida, la percepción de riesgo, los rasgos de personalidad, los patrones de personalidad antisocial y el consumo de otras sustancias en la predicción del consumo de psicoestimulantes. La muestra estuvo formada por 1.177 jóvenes (584 varones y 593 mujeres) de entre 14 y 25 años en España, reclutados aleatoriamente, estratificados por consumo-no consumo de psicoestimulantes (cocaína o éxtasis) alguna vez en la vida. El path que mejor predijo el consumo de psicoestimulantes fue: rasgos de personalidad-patrones de personalidad antisocial- consumo de psicoestimulantes. El siguiente path fue: rasgos de personalidad- patrones de personalidad antisocial-consumo de psicoestimulantes. La percepción de riesgo y la disponibilidad percibida fueron significativas en la predicción pero aportaron una contribución menor. Los resultados de este estudio sugieren que el modelo evaluado es adecuado para la predicción del consumo de psicoestimulantes en jóvenes. Este modelo puede ser de utilidad para desarrollar estrategias preventivas y para identificar a aquellos jóvenes con riesgo de tener problemas relacionados con el consumo de drogasKnowing which factors predict the use of psychostimulant drugs among youths is important for designing preventive programs and the identification of youths with the highest probability of use, to avoid some of the problems that can be derived from it. The purpose of this study is to examine the relationship between perceived availability, risk perception, personality traits, antisocial personality patterns, and use of other substances in the prediction of psychostimulant use. The sample was composed by 1,177 youths (584 males and 593 females) aged 14 to 25 in Spain, recruited randomly, stratified by lifetime use- non use of psychostimulants (cocaine or ecstasy). The path which best predicts psychostimulant use is: Personality traits-legal substance use-cannabis use-psychostimulant use. The next path is: Personality traits-antisocial personality patterns-psychostimulant use. Risk perception and perceived availability were significant in the prediction, but made a smaller contribution. The results of this study suggest that the model evaluated can predict psychostimulant use in youths. This model can be seen as a useful tool for developing preventive strategies and for identifying those youths that are at risk for problems related to drug useThis research was supported by Xunta de Galicia, Servicio Galego de Saúde (SERGAS) by a cooperation agreement between Xunta de Galicia-SERGAS and University of Santiago de Compostela, SpainS

Microbial β-glucosidases from cow rumen metagenome enhance the saccharification of lignocellulose in combination with commercial cellulase cocktail

BACKGROUND: A complete saccharification of plant polymers is the critical step in the efficient production of bio-alcohols. Beta-glucosidases acting in the degradation of intermediate gluco-oligosaccharides produced by cellulases limit the yield of the final product. RESULTS: In the present work, we have identified and then successfully cloned, expressed, purified and characterised 4 highly active beta-glucosidases from fibre-adherent microbial community from the cow rumen. The enzymes were most active at temperatures 45–55°C and pH 4.0-7.0 and exhibited high affinity and activity towards synthetic substrates such as p-nitrophenyl-beta-D-glucopyranoside (pNPbetaG) and pNP-beta-cellobiose, as well as to natural cello-oligosaccharides ranging from cellobiose to cellopentaose. The apparent capability of the most active beta-glucosidase, herein named LAB25g2, was tested for its ability to improve, at low dosage (31.25 units g(-1) dry biomass, using pNPbetaG as substrate), the hydrolysis of pre-treated corn stover (dry matter content of 20%; 350 g glucan kg(-1) dry biomass) in combination with a beta-glucosidase-deficient commercial Trichoderma reseei cellulase cocktail (5 units g(-1) dry biomass in the basis of pNPbetaG). LAB25g2 increased the final hydrolysis yield by a factor of 20% (44.5 ± 1.7% vs. 34.5 ± 1.5% in control conditions) after 96–120 h as compared to control reactions in its absence or in the presence of other commercial beta-glucosidase preparations. The high stability (half-life higher than 5 days at 50°C and pH 5.2) and 2–38000 fold higher (as compared with reported beta-glucosidases) activity towards cello-oligosaccharides may account for its performance in supplementation assays. CONCLUSIONS: The results suggest that beta-glucosidases from yet uncultured bacteria from animal digestomes may be of a potential interest for biotechnological processes related to the effective bio-ethanol production in combination with low dosage of commercial cellulases

Review of Pharmacokinetics and Pharmacogenetics in Atypical Long-Acting Injectable Antipsychotics

Over the last two decades, pharmacogenetics and pharmacokinetics have been increasingly used in clinical practice in Psychiatry due to the high variability regarding response and side effects of antipsychotic drugs. Specifically, long-acting injectable (LAI) antipsychotics have different pharmacokinetic profile than oral formulations due to their sustained release characteristics. In addition, most of these drugs are metabolized by CYP2D6, whose interindividual genetic variability results in different metabolizer status and, consequently, into different plasma concentrations of the drugs. In this context, there is consistent evidence which supports the use of therapeutic drug monitoring (TDM) along with pharmacogenetic tests to improve safety and efficacy of antipsychotic pharmacotherapy. This comprehensive review aims to compile all the available pharmacokinetic and pharmacogenetic data regarding the three major LAI atypical antipsychotics: risperidone, paliperidone and aripiprazole. On the one hand, CYP2D6 metabolizer status influences the pharmacokinetics of LAI aripiprazole, but this relation remains a matter of debate for LAI risperidone and LAI paliperidone. On the other hand, developed population pharmacokinetic (popPK) models showed the influence of body weight or administration site on the pharmacokinetics of these LAI antipsychotics. The combination of pharmacogenetics and pharmacokinetics (including popPK models) leads to a personalized antipsychotic therapy. In this sense, the optimization of these treatments improves the benefit–risk balance and, consequently, patients’ quality of lifeThis project was partially supported by Fundación Española de Farmacia Hospitalaria “Convocatoria de ayudas de proyectos para grupos de trabajo de la SEFH 2021-2022”, Plan Galego de Saude Mental (SERGAS) and Axencia Galega Innovación (Grupos de Potencial Crecimiento IN607B2020/11). Bandín-Vilar E.: Mondelo-García C. and Fernández-Ferreiro A. are grateful to the Carlos III Health Institute for financing their personnel contracts: CM20/00135, JR20/00026 and JR18/00014S

Gobernanza y gestión del agua en el Occidente de México: la metrópoli de Guadalajara

La disponibilidad de agua como tal no es el problema más importante en la gestión del agua. La incertidumbre se sitúa en la capacidad para implementar sistemas de control, distribución y acceso al agua de una forma equitativa. Garantizar el acceso de agua potable a toda la población no es un problema financiero sino político, un asunto de prioridad .Ahora disponemos de un vasto conocimiento y herramientas aplicables en el campo de la hidrología, biotecnología e ingeniería del agua, pero nuestro entendimiento sobre procesos socioeconómicos, culturales y políticos involucrados en la gestión del agua, sigue siendo limitado. En este libro, desde diferentes ángulos, se analizan formas de gestión del agua, escenarios de gobernanza, conflictos sociales y soluciones de carácter sociopolítico y técnico encaminadas a un manejo más sustentable del agua con posibilidades de ser apropiado socialmente. La obra tiene un fuerte componente con tintes de ecología política alrededor de los conflictos por el agua en la metrópoli de Guadalajara y la cuenca Lerma–Chapala–Santiago, sobre todo en aquellos casos donde coinciden situaciones de deterioro ambiental y formas inadecuadas de desarrollo urbano. En las alternativas que se analizan y proponen, se descubre una rica diversidad que encabezan organizaciones sociales, ciudadanos, actores sociopolíticos, universidades e instituciones con diferentes niveles de impacto, vinculación y trayectorias. Se distinguen escalas y formas de gobernanza del agua a nivel de cuenca, zona metropolitana de Guadalajara, municipios y sistemas hidrográficos (microcuencas y sistemas de abastecimiento), además de revisar estilos de desarrollo urbano asociados al manejo del agua con una perspectiva de análisis y de propuesta.ITESO, A.C