Lithium response in bipolar disorder: Epigenome-wide DNA methylation signatures and epigenetic aging.

Lithium (Li) is the first-line treatment for bipolar disorder (BD) even though only 30 % of BD patients are considered excellent responders. The mechanisms by which Li exerts its action are not clearly understood, but it has been suggested that specific epigenetic mechanisms, such as methylation processes, may play a role. In this regard, DNA methylation patterns can be used to estimate epigenetic age (EpiAge), which is accelerated in BD patients and reversed by Li treatment. Our first aim was to compare the DNA methylation profile in peripheral blood between BD patients categorized as excellent responders to Li (Ex-Rp) and non-responders (N-Rp). Secondly, EpiAge was estimated to detect differential age acceleration between the two groups. A total of 130 differentially methylated positions (DMPs) and 16 differentially methylated regions (DMRs) between Ex-Rp (n = 26) and N-Rp (n = 37) were identified (FDR adjusted p-value < 0.05). We found 122 genes mapping the DMPs and DMRs, nine of which (HOXB6, HOXB3, HOXB-AS3, TENM2, CACNA1B, ANK3, EEF2K, CYP1A1, and SORCS2) had previously been linked to Li response. We found genes related to the GSK3ß pathway to be highly represented. Using FUMA, we found enrichment in Gene Ontology Cell Component for the synapse. Gene network analysis highlighted functions related to the cell cycle, nervous system development and function, and gene expression. No significant differences in age acceleration were found between Ex-Rp and N-Rp for any of the epigenetic clocks analysed. Our findings indicate that a specific methylation pattern could determine the response to Li in BD patients. We also found that a significant portion of the differentially methylated genes are closely associated with the GSK3ß pathway, reinforcing the role of this system in Li response. Future longitudinal studies with larger samples will help to elucidate the epigenetic mechanisms underlying Li response.

[Methamphetamine use in chemsex and its consequences on mental health: a descriptive study.] / Uso de metanfetamina en el contexto chemsex y sus consecuencias en la salud mental: un estudio descriptivo.

OBJECTIVE: Chemsex is a term applicable to the use of drugs related to sex among men who have sex with men (MSM). Because it is a recent trend, there is little information about its management and consequences. The aim of the study was to describe the clinical profile of a sample of chemsex users who consulted for treatment. METHODS: This is a longitudinal and retrospective study of 53 patients who consulted for chemsex in an addiction unit of a general hospital in Barcelona, from January 2017 to June 2019. Data was collected from electronic medical records and a descriptive analysis was performed by calculating proportions and means. RESULTS: The most common drug used in chemsex was methamphetamine (81.1%; n=43) and 67.4% (n=29) of these used at least other two drugs. The prevalence of HIV infection was high (71.2%; n=37) and 72.1% (n=41) had psychiatric comorbidity, being the most common psychosis (37.2%; n=16). CONCLUSIONS: Methamphetamine was the most common drug chemsex user's seeked for treatment. Furthermore, there is a high prevalence of HIV diagnosis in this population. Both conditions can enhance the risk of suffering from psychosis and may explain why psychiatric comorbidity is so high in the sample.

OBJETIVO: El fenómeno chemsex es una práctica de consumo de sustancias asociada a las relaciones sexuales en hombres que tienen sexo con hombres. Debido a la novedad que supone, disponemos de poca información en cuanto a su abordaje y pronóstico desde el punto de vista de la salud mental. El objetivo de este estudio fue describir el perfil de una muestra de usuarios de chemsex que solicitaron tratamiento para abandonar el consumo. METODOS: Se realizó un estudio longitudinal retrospectivo de una muestra de 53 sujetos que consultaron en la unidad de adicciones de un hospital de Barcelona en el período entre enero de 2017 y junio de 2019 por consumo de drogas en contexto de chemsex. Los datos se recogieron a través de una revisión de historias clínicas y se realizó un análisis estadístico de tipo descriptivo mediante el cálculo de proporciones y medias. RESULTADOS: La metanfetamina fue la droga principal por la que más frecuentemente se solicitaba tratamiento (81,1%; n=43). De éstos, el 67,4% (n=29) consumía además, como mínimo, otras dos sustancias. El 71,2% (n=37) presentaba infección por VIH. El 72,1% (n=41) de los sujetos presentó comorbilidad psiquiátrica, siendo lo más frecuente la sintomatología psicótica (37,2%; n=16). CONCLUSIONES: Un porcentaje elevado de usuarios de chemsex presentan diagnóstico de VIH y la droga principal más utilizada y por la que más consultaron fue la metanfetamina. Ambas condiciones podrían estar relacionadas con la elevada prevalencia de sintomatología psicótica.

Effects of an integrative approach to bipolar disorders combining psychoeducation, mindfulness-based cognitive therapy and functional remediation: study protocol for a randomized controlled trial / Efectos de un abordaje integral para el trastorno bipolar combinando la psicoeducación, terapia cognitiva basada en el mindfulness y rehabilitación funcional: protocolo para un ensayo clínico controlado y aleatorizado

INTRODUCTION: Bipolar disorder is related to a high level of personal, familial, social and economic burden. There is a need for feasible adjunctive psychological interventions easy to implement in clinical practice in order to enhance aspects that medication alone cannot achieve. This study aims to evaluate the impact of a 12-session adjunctive integrative program designed for patients with bipolar disorder. METHODS: This is a single-blind prospective, randomized controlled trial involving a total of 132 outpatients with bipolar disorder who will be recruited from the Hospital Clinic of Barcelona. All participants will be randomly assigned to two arms. All the patients will receive treatment as usual (TAU) but in addition the experimental group will receive an integrative approach consisting of 12-sessions of 90 min each in which contents of psychoeducation for patients have been combined with a session for family members, and complemented with aspects related to health promotion, mindfulness training, and strategies for cognitive and functional enhancement. The whole sample will be assessed at baseline, after completion (3-months) and at 12 months from baseline regarding demographic and clinical variables, psychosocial and cognitive functioning, wellbeing and quality of life. The primary outcome measure will be improvement in psychosocial functioning. CONCLUSIONS: If the integrative approach is effective, it would allow clinicians to cover different areas that may be affected by bipolar disorder, by means of a brief intervention that can therefore be easily generalized to clinical practice

INTRODUCCIÓN: El trastorno bipolar se asocia a un nivel elevado de carga personal, familiar, social y económica. Existe la necesidad de intervenciones psicológicas complementarias factibles y fáciles de implementar en la práctica clínica para mejorar aspectos que la medicación no consigue alcanzar. Este estudio tiene como objetivo evaluar el impacto de un programa integral de 12 sesiones complementario al tratamiento farmacológico para pacientes con trastorno bipolar. MÉTODOS: Ensayo clínico aleatorizado, controlado, a simple ciego. Serán reclutados del Hospital Clínic de Barcelona 132 pacientes ambulatorios diagnosticados de trastorno bipolar. Los participantes serán asignados aleatoriamente a dos grupos. Todos los pacientes recibirán el tratamiento habitual (TAU) pero, además, el grupo experimental recibirá un abordaje integral que consistirá en 12 sesiones de 90 min en las que se han combinado los contenidos de psicoeducación para pacientes con una sesión para familiares, complementándose con aspectos relacionados con la promoción de la salud, el entrenamiento en atención plena y estrategias para la potenciación cognitiva y funcional. La muestra completa será evaluada al inicio del estudio, a los 3 meses y a los 12 meses de seguimiento respecto a variables sociodemográficas y clínicas, de funcionamiento psicosocial y cognitivo, bienestar y calidad de vida. El principal resultado esperado será la mejoría en el funcionamiento psicosocial. CONCLUSIONES: Si el abordaje integral es efectivo, permitiría a los clínicos cubrir diferentes áreas que pueden verse afectadas por el trastorno bipolar, mediante una breve intervención que, por lo tanto, puede generalizarse fácilmente a la práctica clínica

Effects of an integrative approach to bipolar disorders combining psychoeducation, mindfulness-based cognitive therapy and functional remediation: Study protocol for a randomized controlled trial.

INTRODUCTION: Bipolar disorder is related to a high level of personal, familial, social and economic burden. There is a need for feasible adjunctive psychological interventions easy to implement in clinical practice in order to enhance aspects that medication alone cannot achieve. This study aims to evaluate the impact of a 12-session adjunctive integrative program designed for patients with bipolar disorder. METHODS: This is a single-blind prospective, randomized controlled trial involving a total of 132 outpatients with bipolar disorder who will be recruited from the Hospital Clinic of Barcelona. All participants will be randomly assigned to two arms. All the patients will receive treatment as usual (TAU) but in addition the experimental group will receive an integrative approach consisting of 12-sessions of 90min each in which contents of psychoeducation for patients have been combined with a session for family members, and complemented with aspects related to health promotion, mindfulness training, and strategies for cognitive and functional enhancement. The whole sample will be assessed at baseline, after completion (3-months) and at 12 months from baseline regarding demographic and clinical variables, psychosocial and cognitive functioning, wellbeing and quality of life. The primary outcome measure will be improvement in psychosocial functioning. CONCLUSIONS: If the integrative approach is effective, it would allow clinicians to cover different areas that may be affected by bipolar disorder, by means of a brief intervention that can therefore be easily generalized to clinical practice. TRIAL REGISTRATION: NCT04031560. Date registered July 24, 2019.

Preventing Hospital-Induced Delirium in the ICU.

A patient familiar with strategies for staying oriented after surgery puts them to the test.

Mycobacterium tuberculosis genotypes and predominant clones among the multidrug-resistant isolates in Spain 1998-2005.

Although the incidence of tuberculosis (TB) is gradually decreasing in Spain, there is an increase in the proportion of foreign-born cases. This changing scenario is slowly shifting the local TB epidemiology from endemic to imported cases with an increased risk for multidrug-resistant (MDR) and extensively drug resistant (XDR) strains of Mycobacterium tuberculosis complex. MDR/XDR strains from Spain (n=366 MTBC isolates, 1 strain per patient) isolated between 1998 and 2005 were retained for this retrospective analysis. All strains were analyzed by spoligotyping, while 12-loci MIRU-VNTR data were available for 106 isolates from 2003 to 2005. Demographic, phylogenetic, and epidemiologic analyses using anonymized data were collected and analyzed using the SITVIT2 database. Our study provides with a first snapshot of genetic diversity of MDR/XDR-TB in several autonomous regions of Spain. It highlights significantly more of SIT1/Beijing and SIT66/BOV MDR isolates (5.7% and 7.38% respectively) and increasingly more foreign-born cases from Eastern Europe. Future studies should focus on shared genotypes between Spanish and foreign-born patients to decipher the modes of transmission and risk factors involved, and decipher the proportion of imported cases of active disease versus cases of reactivation of latent TB infection among foreign-born individuals.

Rapid test for identification of a highly transmissible Mycobacterium tuberculosis Beijing strain of sub-Saharan origin.

The development of a rapid test to identify Mycobacterium tuberculosis Beijing isolates and specifically strain GC1237, coming from a sub-Saharan country, is needed due to its alarming wide spread on Gran Canaria Island (Spain). A rapid test that detects IS6110 present between dnaA and dnaN in the Beijing strains and in a specific site for GC1237 (Rv2180c) has been developed. This test would be a useful tool in the surveillance of subsequent cases.

Conspicuous multidrug-resistant Mycobacterium tuberculosis cluster strains do not trespass country borders in Latin America and Spain.

Multidrug-resistant Mycobacterium tuberculosis strain diversity in Ibero-America was examined by comparing extant genotype collections in national or state tuberculosis networks. To this end, genotypes from over 1000 patients with multidrug-resistant tuberculosis diagnosed from 2004 through 2008 in Argentina, Brazil, Chile, Colombia, Venezuela and Spain were compared in a database constructed ad hoc. Most of the 116 clusters identified by IS6110 restriction fragment length polymorphism were small and restricted to individual countries. The three largest clusters, of 116, 49 and 25 patients, were found in Argentina and corresponded to previously documented locally-epidemic strains. Only 13 small clusters involved more than one country, altogether accounting for 41 patients, of whom 13 were, in turn, immigrants from Latin American countries different from those participating in the study (Peru, Ecuador and Bolivia). Most of these international clusters belonged either to the emerging RD(Rio) LAM lineage or to the Haarlem family of M. tuberculosis and four were further split by country when analyzed with spoligotyping and rifampin resistance-conferring mutations, suggesting that they did not represent ongoing transnational transmission events. The Beijing genotype accounted for 1.3% and 10.2% of patients with multidrug-resistant tuberculosis in Latin America and Spain, respectively, including one international cluster of two cases. In brief, Euro-American genotypes were widely predominant among multidrug-resistant M. tuberculosis strains in Ibero-America, reflecting closely their predominance in the general M. tuberculosis population in the region, and no evidence was found of acknowledged outbreak strains trespassing country borders.

Long-term molecular surveillance of multidrug-resistant tuberculosis in Spain.

The data presented here span 11 years (1998-2008) of monitoring of multidrug-resistant tuberculosis (MDR-TB) clustering through molecular typing techniques in Spain. The molecular and epidemiological data of 480 multidrug-resistant Mycobacterium tuberculosis complex isolates were analyzed. Thirty-one clusters involving 157 (32.7%) patients were identified. The proportion of immigrants increased substantially over the study period reaching 65% in 2008; however, the clustering rate remained stable indicating that local transmission was little influenced by imported MDR-TB. The three major clusters respond to the persistence of two autochthonous strains throughout the study period and an extensively drug-resistant (XDR) Mycobacterium bovis outbreak with only two cases was reported since 2002. Molecular and epidemiological evidence for the importation of new strains and their spread within the community was found. Immigrant-only clusters most often grouped patients infected abroad with strains belonging to rare spoligotypes. Conversely, widespread spoligotypes of the Latin-American and Mediterranean (LAM) and Haarlem families were responsible for the majority of the MDR-TB local transmission. The demonstration of clusters spanning several Spanish regions that have been ongoing throughout the study period makes it advisable to maintain a continuous molecular surveillance in order to monitor the spread of MDR-TB.

Noachian and more recent phyllosilicates in impact craters on Mars.

Hundreds of impact craters on Mars contain diverse phyllosilicates, interpreted as excavation products of preexisting subsurface deposits following impact and crater formation. This has been used to argue that the conditions conducive to phyllosilicate synthesis, which require the presence of abundant and long-lasting liquid water, were only met early in the history of the planet, during the Noachian period (> 3.6 Gy ago), and that aqueous environments were widespread then. Here we test this hypothesis by examining the excavation process of hydrated minerals by impact events on Mars and analyzing the stability of phyllosilicates against the impact-induced thermal shock. To do so, we first compare the infrared spectra of thermally altered phyllosilicates with those of hydrated minerals known to occur in craters on Mars and then analyze the postshock temperatures reached during impact crater excavation. Our results show that phyllosilicates can resist the postshock temperatures almost everywhere in the crater, except under particular conditions in a central area in and near the point of impact. We conclude that most phyllosilicates detected inside impact craters on Mars are consistent with excavated preexisting sediments, supporting the hypothesis of a primeval and long-lasting global aqueous environment. When our analyses are applied to specific impact craters on Mars, we are able to identify both pre- and postimpact phyllosilicates, therefore extending the time of local phyllosilicate synthesis to post-Noachian times.

Unsuspected and extensive transmission of a drug-susceptible Mycobacterium tuberculosis strain.

BACKGROUND: A large and unsuspected tuberculosis outbreak involving 18.7% of the total of the tuberculosis cases studied, was detected in a population-based molecular epidemiological study performed in Zaragoza (Spain) from 2001 to 2004. METHODS: The Mycobacterium tuberculosis drug-susceptible strain, named MTZ strain, was genetically characterized by IS6110-RFLP, Spoligotyping and by MIRU-VNTR typing and the genetic patterns obtained were compared with those included in international databases. The characteristics of the affected patients, in an attempt to understand why the MTZ strain was so highly transmitted among the population were also analyzed. RESULTS: The genetic profile of the MTZ strain was rare and not widely distributed in our area or elsewhere. The patients affected did not show any notable risk factor for TB. CONCLUSION: The M. tuberculosis strain MTZ, might have particular transmissibility or virulence properties, and we believe that greater focus should be placed on stopping its widespread dissemination.

[Cryptosporidium hominis diarrhea outbreak and transmission linked to diaper infant use]. / Brote de diarrea y transmisión de Cryptosporidium hominis asociados al uso de pañal en niños.

BACKGROUND AND OBJECTIVE: On the basis of several cases of cryptosporidiosis detected in a child day-care center, we stablished the extent of the outbreak and investigated causes of parasite transmission. PATIENTS AND METHOD: A retrospective cohort study was designed on all children attending day-care center and care givers to determine their infection status and identify risk factors associated to the outbreak. RESULTS: 24 cases of cryptosporidiosis were detected, with an attack rate of 0.46 (24/52); 12 of them were parasitologycally confirmed. All care givers were negative for Cryptosporidium and none of them reported symptoms of acute gastroenteritis. Transmission pattern was compatible with person to person modes. Among the factors investigated, two were associated with the risk of disease: diaper wear (relative risk = 2.06; p = 0.059); and diarrhea in relatives (relative risk = 2.05; p = 0.01). In all confirmed cases, Cryptosporidium hominis (previously known as C. parvum, genotype 1), was identified. CONCLUSIONS: Cryptosporidiosis should be considered as a possible cause of outbreaks of gastroenteritis at day-care centers. Increasing care on diaper changing practices, specially over children with diarrhea, may be the key factor to prevent transmission of Cryptosporidium.

Brote de diarrea y transmisión de Cryptosporidium hominis asociados al uso de pañal en niños / Cryptosporidium hominis diarrhea outbreak and transmission linked to diaper infant use

Fundamento y objetivo: Ante la aparición de varios casos de criptosporidiosis en niños de una guardería, se estudió la extensión del brote y las causas de transmisión del parásito. Pacientes y método: Se diseñó un estudio de cohortes retrospectivo en el que se incluyó a todos los niños que asistían a la guardería en ese momento y a las cuidadoras, para determinar su estado de parasitación e identificar los factores de riesgo asociados al brote. Resultados: Durante el período de estudio se detectaron 24 casos de criptosporidiosis, 12 de ellos confirmados parasitológicamente, con una tasa de ataque de 0,46 (24/52). Ninguna de las cuidadoras presentó síntomas ni fue positiva al parásito. La transmisión de la infección presentó un patrón indicativo de mecanismos de persona a persona. Dentro de los factores de riesgo estudiados, los 2 únicos que pudieron relacionarse con la enfermedad fueron el uso de pañal (riesgo relativo = 2,06; p = 0,059) y la diarrea en familiares (riesgo relativo = 2,05; p = 0,01). La especie encontrada en los casos confirmados fue Cryptosporidium hominis (antes conocido como C. parvum, genotipo 1). Conclusiones: La criptosporidiosis debería contemplarse como posible causa de brotes de gastroenteritis en guarderías. Aumentar las precauciones higiénicas en las maniobras de cambio de pañal, especialmente en niños con diarrea, parece determinante para evitar la transmisión de Cryptosporidium

Background and objective: On the basis of several cases of cryptosporidiosis detected in a child day-care center, we stablished the extent of the outbreak and investigated causes of parasite transmission. Patients and method: A retrospective cohort study was designed on all children attending day-care center and care givers to determine their infection status and identify risk factors associated to the outbreak. Results: 24 cases of cryptosporidiosis were detected, with an attack rate of 0.46 (24/52); 12 of them were parasitologycally confirmed. All care givers were negative for Cryptosporidium and none of them reported symptoms of acute gastroenteritis. Transmission pattern was compatible with person to person modes. Among the factors investigated, two were associated with the risk of disease: diaper wear (relative risk = 2.06; p = 0.059); and diarrhea in relatives (relative risk = 2.05; p = 0.01). In all confirmed cases, Cryptosporidium hominis (previously known as C. parvum, genotype 1), was identified. Conclusions: Cryptosporidiosis should be considered as a possible cause of outbreaks of gastroenteritis at day-care centers. Increasing care on diaper changing practices, specially over children with diarrhea, may be the key factor to prevent transmission of Cryptosporidium

Molecular characterization of Mycobacterium tuberculosis complex isolates from wild ungulates in south-central Spain.

The role of European wild ungulates in the epidemiology of tuberculosis (TB) is still under discussion. This study describes the geographical distribution and molecular typing of 77 Mycobacterium tuberculosis complex isolates belonging either to M. bovis or to M. caprae, cultivated from hunter harvested red deer (Cervus elaphus) and European wild boar (Sus scrofa) in 24 Spanish localities, and compares them with spoligotypes detected previously in humans, livestock or wild animals, as described in the literature. The distribution of the molecular type patterns suggests that the population of M. tuberculosis complex strains isolated from Spanish wild ungulates is spatially structured despite the lack of important geographical barriers and despite the increasingly frequent wildlife translocations. Red deer and the European wild boar can share the same molecular types in localities in which the M. tuberculosis complex was isolated from both species. Strains of bovine and caprine origin do circulate in the same local wildlife populations. Six out of 11 spoligotypes were similar to types described in human cases. The isolation of TB strains in fenced estates from wild animals that have not had contact with domestic livestock for at least the past two decades, strongly suggests that the M. tuberculosis complex is able to survive in these populations. Therefore, wildlife including cervids and the wild boar need to be considered in the epidemiology and control of tuberculosis.