Conectividad funcional y procesos inhibitorios en las recaídas en el consumo de alcohol

El consumo crónico de alcohol supone ciertas disfunciones cognitivas, aunque los déficits ejecutivos son centrales y están relacionados con el curso de la enfermedad. Específicamente, el control inhibitorio, cognitivo y conductual o la capacidad de toma de decisiones resultan clave en el éxito terapéutico y mantenimiento de la abstinencia. Estas alteraciones se han asociado a deficiencias en el funcionamiento neural tanto en estados interoceptivos de reposo, como durante procesos cognitivos asociados a la inhibición, el control atencional o la toma de decisiones. Por lo tanto, se plantean los siguientes objetivos en este trabajo: 1. Evaluar en contextos relacionados con la sustancia la toma de decisión léxica y la inhibición motora. 2. Evaluar la actividad psicofisiológica subyacente a procesos léxicos e inhibitorios y en presencia de estímulos asociados a la sustancia. 3. Evaluar la actividad cerebral en reposo en términos de oscilaciones y conectividad funcional..

Development of a screening test for cognitive impairment in alcoholic population: TEDCA.

ntroducción. Numerosos estudios han encontrado alteraciones cognitivas en pacientes con historia de trastorno por consumo de alcohol, afectando su funcionamiento psicosocial y consecución de objetivos terapéuticos. Para identificar estas afectaciones se han utilizado pruebas de cribado cognitivo a pesar de que no han sido diseñadas para esta población, aumentando el riesgo de error. Objetivo. Valorar los principales déficits cognitivos en pacientes con historia de trastorno por consumo de alcohol, para desarrollar una prueba de cribado de alteraciones cognitivas específica para estos pacientes. Metodología. El TEDCA (Test de detección de deterioro cognitivo en alcoholismo) se diseñó en base a tres dimensiones: Cognición Viso-espacial, Memoria/Aprendizaje y Función Ejecutiva. El estudio se dividió en dos fases: En la fase 1 se seleccionaron las pruebas con mayor capacidad de discriminación entre pacientes con diferentes niveles de afectación cognitiva, y en la fase 2 se realizaron los análisis de validez y fiabilidad. La muestra estuvo formada por 248 participantes, 88 controles (fase 2) y 160 pacientes (fase 1: n=70 y fase 2: n=90). Resultados. El TEDCA obtuvo una fiabilidad elevada (alfa de Cronbach 0.754), el análisis factorial confirmó la presencia de las 3 dimensiones definidas previamente, dis- criminó entre pacientes y controles, y presenta una buena validez diagnóstica de afectación cognitiva. Conclusiones. El TEDCA es una nueva prueba de cribado, que permite identificar la posible presencia de afectación cognitiva en pacientes con historia de trastorno por onsumo de alcohol, que puede ser utilizado en los ámbitos de psiquiatría, atención primaria e investigación.post-print146 K

Agricultural intensification and the evolution of host specialism in the enteric pathogen Campylobacter jejuni.

Modern agriculture has dramatically changed the distribution of animal species on Earth. Changes to host ecology have a major impact on the microbiota, potentially increasing the risk of zoonotic pathogens being transmitted to humans, but the impact of intensive livestock production on host-associated bacteria has rarely been studied. Here, we use large isolate collections and comparative genomics techniques, linked to phenotype studies, to understand the timescale and genomic adaptations associated with the proliferation of the most common food-born bacterial pathogen (Campylobacter jejuni) in the most prolific agricultural mammal (cattle). Our findings reveal the emergence of cattle specialist C. jejuni lineages from a background of host generalist strains that coincided with the dramatic rise in cattle numbers in the 20th century. Cattle adaptation was associated with horizontal gene transfer and significant gene gain and loss. This may be related to differences in host diet, anatomy, and physiology, leading to the proliferation of globally disseminated cattle specialists of major public health importance. This work highlights how genomic plasticity can allow important zoonotic pathogens to exploit altered niches in the face of anthropogenic change and provides information for mitigating some of the risks posed by modern agricultural systems

Associations of hypomagnesemia in patients seeking a first treatment of alcohol use disorder

Introduction: Hypomagnesemia (hypoMg) has not yet been extensively studied in alcohol use disorder (AUD) . We hypothesize that chronic, excessive alcohol consumption favors oxidative stress and pro-inflammatory alterations that may be exacerbated by hypoMg. The objective of this study was to analyze the prevalence and associations of hypoMg in AUD.Patients and Methods: Cross-sectional study in patients admitted for a first treatment of AUD in six tertiary centers between 2013 and 2020. Socio-demographic, alcohol use characteristics, and blood parameters were ascertained at admission.Results: 753 patients (71% men) were eligible; age at admission was 48 years [IQR, 41-56 years]. Prevalence of hypoMg was 11.2%, higher than that observed for hypocalcemia (9.3%), hyponatremia (5.6%), and hypokalemia (2.8%). HypoMg was associated with older age, longer duration of AUD, anemia, higher erythrocyte sedimen-tation rate, gamma-glutamyl transpeptidase, glucose levels, advanced liver fibrosis (FIB-4 >= 3.25) and estimated glomerular filtration rate (eGFR) < 60 mL/min. In multivariate analysis, advanced liver fibrosis (OR, 8.91; 95% CI, 3.3-23.9) and eGFR < 60 mL (OR, 5.2; 95% CI, 1.0-26.2) were the only factors associated with hypoMg.Conclusions: Mg deficiency in AUD is associated with liver damage and glomerular dysfunction suggesting that both comorbidities should be assessed in the course of serum hypoMg

Conservation Patterns of HIV-1 RT Connection and RNase H Domains: Identification of New Mutations in NRTI-Treated Patients

Background: Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings: We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naıve and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher’s exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions: This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Using a software as a service program in sales-marketing: a case study on Odoo

With the development of technology, implicitly of the fast and easy access to information, the requirements and exigencies of the customers have changed. The customer asks for much more information about a product before deciding to buy it, and a prompt response from the sales team will tip the balance decisively in favor of the seller. The success of an efficient sales team is represented by addressing to the right customers at the right time and in the right way. In the paper we analyzed how the Odoo program can be implemented within the sales-marketing department. Using specific modules, we followed the information flow of the marketing process, from market prospecting and to the registration in accounting of the invoices resulting from the orders made. We also presented the way in which marketing campaigns can be carried out, depending on the target group to which it is addressed

Towards recovery : Therapeutic approaches to improve the treatment of alcohol use disorder

Currently, the best evidence-based treatments for alcohol dependence are those developed in multidisciplinary programmes based on a cognitive-behavioural approach, including psychological, sociological, and medical dimensions. However, recovery is not always achieved. The percentage of individuals who abandon and relapse is high throughout the process and an adequate state of wellbeing is not always found. This paper outlines some of the complements or techniques that could be incorporated to the most common treatments to enhance behavioural change, taking into account long-term outcomes. Thus, the text highlights the importance of considering recovery as the culmination of the process of change towards improved health, wellbeing, and self-directed life purpose, rather than just abstinenc