Validation of the Spanish version of the multifaceted empathy test: comparison between cannabis use effects and controls in social cognition.

OBJECTIVE: While social cognition is shown to be impaired in several mental disorders, the effects of cannabis on social cognition are still not clear. Past studies have used the multifaceted empathy test (MET) to study social cognition. This study aims to test the validity of the MET Spanish version and to evaluate the effects of cannabis use on social cognition. METHODS: In total 116 participants from a Cannabis Social Club (CSC) completed the MET and the reading the mind in the eyes test (RMET) under the effects of cannabis and were compared to 86 university students (control group). Internal consistency and convergent validity were assessed. Cognitive empathy (CE) and emotional empathy (EE) were tested in both groups. RESULTS: The MET CE scale shows low internal consistency, while the EE scale shows high internal consistency. Items showed similar difficulty for both groups. Cannabis users showed deficient overall emotional recognition, with reduced scores associated with positive stimuli. Overall scores for EE were similar for both groups, but the experimental group scored lower with negative stimuli when compared to controls. CONCLUSION: This study validates the MET Spanish version for its use in future studies. Results confirmed deficient emotional recognition in cannabis users and a dampened reaction to negative stimuli for the first time.

Body map stories from Colombia: experiences of people affected by leprosy and the influence of peers during diagnosis and treatment.

INTRODUCTION: Almost one third of people affected by leprosy in Colombia suffer from disability, which often results from delayed diagnosis and treatment. We aimed to explore the experience of people affected by leprosy during the process of diagnosis and treatment and if and how this experience was influenced by peers. METHODS: A qualitative study using body map stories was conducted from October 2019 to February 2020 in Colombia. Adult people affected by leprosy were recruited through patient associations in different cities. We conducted three sessions with an average duration of 2-3 h per participant, during which the participants created a painted map of their body and chose symbols to represent their experience, while being engaged in an informal interview. The sessions were audio recorded, transcribed verbatim and analyzed thematically by an interdisciplinary team, consisting of physicians, social workers and a person affected by leprosy. RESULTS: The 17 study participants (11 female) were aged 20 to 70 years. Leprosy-related manifestations ranged from no to advanced disability. Some participants were active members of associations for people affected by leprosy. Three main themes were identified during analysis: (1) A long pathway to diagnosis, (2) Therapy as a double-edged sword and (3) The influence of other people affected by leprosy. The participants described an often years-long process until being diagnosed, which was marked by insecurities, repeated misdiagnosis, and worsening mental and physical health. Delayed diagnosis was related to late health care seeking, but also to inadequate health communication, lack of leprosy-related knowledge and negligence among health care workers. A high desire to cure motivated the participants to take their medication rigorously, despite the high treatment burden. Support from peers, either within the own social environment or provided from associations, contributed to a faster diagnosis and increased therapy adherence. Peers helped to recognize the symptoms, urged patients to seek care, recommended physicians with leprosy-related knowledge and provided a realistic example of both disease severity and curability. CONCLUSION: People affected by leprosy experience a significant burden during the process of diagnosis and treatment. Involving well-trained peers could foster early diagnosis, treatment compliance and prevention of disability.

Spanish versions and validation of a series of rating scales and visual analogue scales to assess the subjective effects of cannabis.

Cannabis is being legalized for medical and recreational purposes all around the world. However, the understanding of the psychological effects of cannabis is still limited, and it has been previously linked to mental disorders such as schizophrenia. Lately, new scales have been created and adapted to measure its psychological effects. The aim of this study is to create Spanish versions of some of these scales and test their psychometric characteristics. One hundred sixteen participants were recruited from Cannabis Social Clubs (CSC) in Barcelona, Spain. Participants under the effects of their own cannabis completed the Cannabis Experience Questionnaire-modified version (CEQ-mv), Addiction Research Centre Inventory-18 (ARCI-18), Psychotomimetic States Inventory (PSI) and Visual Analogue Scales (VAS). Questionnaires were completed in the CSC, providing a naturalistic setting for the study. Exploratory factor analysis and internal consistency were analyzed. PSI was reduced from a 6-factor to a 4-factor model with adequate to low reliability, ARCI-18 was reduced from a 3-factor to a 2-factor model with good reliability, and VAS were reduced from a 4-factor to a 3-factor model, also with good reliability. These questionnaires showed adequate reliability and can be used in future studies to test the subjective effects of cannabis in clinical and naturalistic settings.

Prevalence of Chagas disease in Latin American pregnant women in Madrid, Spain: A multicentre cross-sectional study from 2011 to 2016.

OBJECTIVE: The aim of this study is to assess Trypanosoma cruzi infection prevalence among pregnant migrants living in Madrid according to the country of origin and to assess screening coverage in this at-risk population. METHODS: Retrospective multicentre cross-sectional study conducted from January 2011 to December 2016 in eight Madrid hospitals. Each hospital reviewed their microbiology data records to assess the screening coverage and serological diagnosis in all pregnant women coming from endemic areas. RESULTS: From 2011 to 2016, 149,470 deliveries were attended at the eight hospitals, and 11,048 pregnant women were screened for Chagas disease. Most cases (93.5%) were in women from Bolivia, who also showed the highest prevalence (12.4%, 95% confidence interval: 9.9-15.0). Pooled prevalence amongst the screened women was 2.9% (95% CI: 1.8-4.1). Chagas disease screening coverage varied greatly between centres, with a pooled mean coverage of 47% (95% CI: 37%-57%; 73% [95% CI: 63%-82%] for those centres with universal screening vs. 10% [95% CI: 6%-15%] for those with a selective screening approach; p < 0.001). CONCLUSION: Our study provides useful data for policy makers and epidemiologists in a non-endemic area without congenital Chagas screening programmes.

Toward the use of novel alternative methods in epilepsy modeling and drug discovery.

Epilepsy is a chronic brain disease and, considering the amount of people affected of all ages worldwide, one of the most common neurological disorders. Over 20 novel antiseizure medications (ASMs) have been released since 1993, yet despite substantial advancements in our understanding of the molecular mechanisms behind epileptogenesis, over one-third of patients continue to be resistant to available therapies. This is partially explained by the fact that the majority of existing medicines only address seizure suppression rather than underlying processes. Understanding the origin of this neurological illness requires conducting human neurological and genetic studies. However, the limitation of sample sizes, ethical concerns, and the requirement for appropriate controls (many patients have already had anti-epileptic medication exposure) in human clinical trials underscore the requirement for supplemental models. So far, mammalian models of epilepsy have helped to shed light on the underlying causes of the condition, but the high costs related to breeding of the animals, low throughput, and regulatory restrictions on their research limit their usefulness in drug screening. Here, we present an overview of the state of art in epilepsy modeling describing gold standard animal models used up to date and review the possible alternatives for this research field. Our focus will be mainly on ex vivo, in vitro, and in vivo larval zebrafish models contributing to the 3R in epilepsy modeling and drug screening. We provide a description of pharmacological and genetic methods currently available but also on the possibilities offered by the continued development in gene editing methodologies, especially CRISPR/Cas9-based, for high-throughput disease modeling and anti-epileptic drugs testing.

Ivermectin Effect on In-Hospital Mortality and Need for Respiratory Support in COVID-19 Pneumonia: Propensity Score-Matched Retrospective Study.

INTRODUCTION: There is negligible evidence on the efficacy of ivermectin for treating COVID-19 pneumonia. This study aimed to assess the efficacy of ivermectin for pre-emptively treating Strongyloides stercoralis hyperinfection syndrome in order to reduce mortality and the need for respiratory support in patients hospitalized for COVID-19. METHODS: This single-center, observational, retrospective study included patients admitted with COVID-19 pneumonia at Hospital Vega Baja from 23 February 2020 to 14 March 2021. Because strongyloidiasis is endemic to our area, medical criteria support empiric administration of a single, 200 µg/kg dose of ivermectin to prevent Strongyloides hyperinfection syndrome. The outcome was a composite of all-cause in-hospital mortality and the need for respiratory support. RESULTS: Of 1167 patients in the cohort, 96 received ivermectin. After propensity score matching, we included 192 patients. The composite outcome of in-hospital mortality or need for respiratory support occurred in 41.7% of the control group (40/96) and 34.4% (33/96) of the ivermectin group. Ivermectin was not associated with the outcome of interest (adjusted odds ratio [aOR] 0.77, 95% confidence interval [CI] 0.35, 1.69; p = 0.52). The factors independently associated with this endpoint were oxygen saturation (aOR 0.78, 95% CI 0.68, 0.89, p < 0.001) and C-reactive protein at admission (aOR: 1.09, 95% CI 1.03, 1.16, p < 0.001). CONCLUSIONS: In hospitalized patients with COVID-19 pneumonia, ivermectin at a single dose for pre-emptively treating Strongyloides stercoralis is not effective in reducing mortality or the need for respiratory support measures.

Knowledge about Chagas Disease among Family and Community Medicine Residents in a Non-Endemic Region: A Cross-Sectional Study.

Chagas disease (CD) is a parasitic disease endemic to continental Latin America that has globalized in recent years. The most relevant mechanisms of transmission of CD in non-endemic countries are transfusion with infected blood and mother-to-child transmission. There is limited information regarding practicing physicians' knowledge of CD transmission, clinical presentation, and treatment in non-endemic countries, including Spain. Our objective was to analyze the level of knowledge about CD in family and community medicine residents and how it has evolved over the last 5 years. A cross-sectional study was performed in the framework of the training program for family and community medicine specialists in Alicante, Spain. Convenience sampling was used to enroll 214 fourth-year family and community medicine residents from 2016 to 2020. Participants completed the validated Chagas Level of Knowledge Scale questionnaire prior to attending the seminar "Health Care for the Immigrant Population." The mean score on the scale was 7.1/10 points. Only 12 participants (5.6%) answered all questions correctly. Resident physicians who reported having received prior information on CD scored better than those who were not informed (mean, 7.2 versus 6.1 points). Participants from Latin America had scores similar to those of the rest of the participants. Over the 5-year study period, questionnaire scores tended to increase. Knowledge about CD among family and community medicine residents has improved in recent years, although it is still not optimal. Specific training on CD during specialized health care training is warranted.

Understanding the widespread use of veterinary ivermectin for Chagas disease, underlying factors and implications for the COVID-19 pandemic: a convergent mixed-methods study.

OBJECTIVES: Veterinary ivermectin (vet-IVM) has been used widely in Latin America against COVID-19, despite the lack of scientific evidence and potential risks. Widespread vet-IVM intake was also discovered against Chagas disease during a study in Bolivia prior to the pandemic. All vet-IVM-related data were extracted to understand this phenomenon, its extent and underlying factors and to discuss potential implications for the current pandemic. DESIGN: A convergent mixed-methods study design including a survey, qualitative in-depth interviews (IDI) and focus group discussions (FGD). SETTING: A cross-sectional study conducted in 2018 covering the geographic area of Monteagudo, an endemic municipality for Chagas disease. PARTICIPANTS: A total of 669 adult household representatives from 26 communities participated in the survey, supplemented by 14 IDI and 2 FGD among patients, relatives and key informants. RESULTS: 9 IDI and 2 FGD contained narratives on vet-IVM use against Chagas disease. Five main themes emerged: (1) the extent of the vet-IVM phenomenon, (2) the perception of vet-IVM as a treatment for Chagas disease, (3) the vet-IVM market and the controversial role of stakeholders, (4) concerns about potential adverse events and (5) underlying factors of vet-IVM use against Chagas disease.In quantitative analysis, 28% of participants seropositive for Chagas disease had taken vet-IVM. Factors associated with multivariate analysis were advanced age (OR 17.01, 95 CI 1.24 to 36.55, p=0.027 for age above 60 years), the experience of someone close as information source (OR 3.13, 95 CI 1.62 to 5.02, p<0.001), seropositivity for Chagas disease (OR 3.89, 95 CI 1.39 to 6.20, p=0.005) and citing the unavailability of benznidazole as perceived healthcare barrier (OR 2.3, 95 CI 1.45 to 5.18, p=0.002). Participants with an academic education were less likely to report vet-IVM intake (OR 0.12, 95 CI 0.01 to 0.78, p=0.029). CONCLUSIONS: Social determinants of health, the unavailability of treatment and a wonder drug image might contribute to the phenomenon of vet-IVM.

Estimating chagas disease prevalence and number of underdiagnosed, and undertreated individuals in Spain.

BACKGROUND: Chagas disease constitutes a public health problem, and Spain is the non-endemic country with the highest burden of disease outside the Americas. It represents a model for non-endemic countries regarding health policies to control the disease. This study is aimed to generate estimates of the T.cruzi prevalence and the number of undetected and untreated individuals with the infection in Spain and to compare them with the actual number of cases reported by official sources. METHODS: Using aggregate data collected from the literature and official sources (Spanish National Statistics Institute; Spanish Agency of Medicines and Medical Devices) from 2010 to 2018, this study estimates the number of Chagas disease cases, plus the underdiagnosis and undertreatment rates. RESULTS: We estimated that 55,367 out of 2,602,285 migrants originally from endemic countries were living with Chagas disease in Spain in 2018, accounting for a prevalence of 2.1%. Only 1% of these cases(613/455,566) were children aged 14 years or less resulting in a prevalence of 0.1%. Bolivian migrants accounted for 53.9% of the total estimated cases. The index of underdiagnosis and undertreatment were heterogeneous across different Spanish autonomous regions, but the overall index of underdiagnosis was around 71%, and the overall index of undertreatment was 82.5% in patients aged 15 years or older, and 60% in children. CONCLUSION: The burden of Chagas disease in Spain is considerable. Index of underdiagnosis and undertreatment are high, particularly in women of childbearing age, but they have improved in children since the implementation of antenatal screening programmes.

Delta Opioid Receptor in Astrocytes Contributes to Neuropathic Cold Pain and Analgesic Tolerance in Female Mice.

Background: The delta opioid receptor (DOR) contributes to pain control, and a major challenge is the identification of DOR populations that control pain, analgesia, and tolerance. Astrocytes are known as important cells in the pathophysiology of chronic pain, and many studies report an increased prevalence of pain in women. However, the implication of astrocytic DOR in neuropathic pain and analgesia, as well as the influence of sex in this receptor activity, remains unknown. Experimental Approach: We developed a novel conditional knockout (cKO) mouse line wherein DOR is deleted in astrocytes (named GFAP-DOR-KO), and investigated neuropathic mechanical allodynia as well as analgesia and analgesic tolerance in mutant male and female mice. Neuropathic cold allodynia was also characterized in mice of both sexes lacking DOR either in astrocytes or constitutively. Results: Neuropathic mechanical allodynia was similar in GFAP-DOR-KO and floxed DOR control mice, and the DOR agonist SNC80 produced analgesia in mutant mice of both sexes. Interestingly, analgesic tolerance developed in cKO males and was abolished in cKO females. Cold neuropathic allodynia was reduced in mice with decreased DOR in astrocytes. By contrast, cold allodynia was exacerbated in full DOR KO females. Conclusions: These findings show that astrocytic DOR has a prominent role in promoting cold allodynia and analgesic tolerance in females, while overall DOR activity was protective. Altogether this suggests that endogenous- and exogenous-mediated DOR activity in astrocytes worsens neuropathic allodynia while DOR activity in other cells attenuates this form of pain. In conclusion, our results show a sex-specific implication of astrocytic DOR in neuropathic pain and analgesic tolerance. These findings open new avenues for developing tailored DOR-mediated analgesic strategies.

Chagas Disease-Related Mortality in Spain, 1997 to 2018.

BACKGROUND: Chagas disease (CD) is associated with excess mortality in infected people in endemic countries, but little information is available in non-endemic countries. The aim of the study was to analyze mortality in patients admitted to the hospital with CD in Spain. METHODS: A retrospective, observational study using the Spanish National Hospital Discharge Database. We used the CD diagnostic codes of the 9th and 10th International Classification of Diseases to retrieve CD cases from the national public registry from 1997 to 2018. RESULTS: Of the 5022 hospital admissions in people with CD, there were 56 deaths (case fatality rate (CFR) 1.1%, 95% confidence interval (CI) 0.8%, 1.4%), 20 (35.7%) of which were considered directly related to CD. The median age was higher in those who died (54.5 vs. 38 years; p < 0.001). The CFR increased with age, peaking in the 70-79-year (7.9%, odds ratio (OR) 6.27, 95% CI 1.27, 30.90) and 80-89-year (16.7%, OR 14.7, 95% CI 2.70, 79.90) age groups. Men comprised a higher proportion of those who died compared to survivors (50% vs. 22.6%; p < 0.001). Non-survivors were more likely to have neoplasms (19.6% vs. 3.4%; p < 0.001), heart failure (17.9% vs. 7.2%; p = 0.002), diabetes (12.5% vs. 3.7%; p = 0.001), chronic kidney failure (8.9% vs. 1.6%; p < 0.001), and HIV (8.9% vs. 0.8%; p < 0.001). In the multivariable analysis, the variables associated with mortality were age (adjusted OR (aOR) 1.05; 95% CI: 1.03, 1.07), male sex (aOR 1.79, 95% CI 1.03, 3.14), cancer (aOR: 4.84, 95% CI 2.13, 11.22), and HIV infection (aOR 14.10 95% CI 4.88, 40.73). CONCLUSIONS: The case fatality rate of CD hospitalization was about 1%. The mortality risk increased with age, male sex, cancer, and HIV infection.

Community-based screening of Chagas disease among Latin American migrants in a non-endemic country: an observational study.

BACKGROUND: Chagas disease is a parasitic disease endemic to Latin America, but it has become a disease of global concern due to migration flows. Asymptomatic carriers may host the parasite for years, without knowing they are infected. The aim of this study is to assess prevalence of Chagas disease and evaluate the participants' level of knowledge between Latin American migrants attending a community-based screening campaign. METHODS: Three community-based campaigns were performed in Alicante (Spain) in 2016, 2017 and 2018, including educational chats and blood tests for Trypanosoma cruzi serology. Participants completed a questionnaire assessing knowledge about the mechanisms of transmission, disease presentation, diagnosis, and treatment. People seropositive for T. cruzi underwent diagnostic confirmation by two different tests. Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios (aORs), adjusting for age, sex, and time in Spain. RESULTS: A total of 596 participants were included in the study; 17% were aged under 18 years. Prevalence in adults was 11% [54/496; 95% confidence interval (CI): 8.3-14.5%] versus 0% among children. All but one case were in Bolivians. Diagnosis was independently associated with having been born in Bolivia (aOR: 102, 95% CI: 13-781) and a primary school-level education (aOR: 2.40, 95% CI: 1.14-5.06). Of 54 people diagnosed with Chagas disease (most of whom were asymptomatic), 42 (77.7%) returned to the clinic at least once, and 24 (44.4%) received treatment. Multivariable analysis showed that coming from Argentina (aOR: 13, 95% CI: 1.61-1188) or Bolivia (aOR: 1.90, 95% CI: 1.19-3.39) and having received information about Chagas disease in Spain (aOR: 4.63, 95% CI: 2.54-8.97) were associated with a good level of knowledge on the disease. Having primary level studies (aOR: 0.59, 95% CI: 0.34-0.98) and coming from Ecuador (aOR: 4.63, 95% CI: 2.52-847) were independently associated with a lower level of knowledge. CONCLUSIONS: Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected, asymptomatic individuals.

Efectividad del cepillo dental eléctrico versus manual para la remoción de biofilm en pacientes con síndrome de Down / Effectiveness of electric versus manual toothbrush for biofilm removal in patients with Down syndrome

Introducción: La salud oral en pacientes con síndrome de Down (SD) es un reto, ya que las alteraciones en la motricidad ocasionadas por la discapacidad intelectual (DI) hacen que tareas como la remoción del biofilm oral o placa dentobacteriana (PDB) con el cepillado sea deficiente. La efectividad de los cepillos eléctricos (CE) comparada con los manuales (CM) en afectados con SD sigue siendo un tema debatible ya que no se ha encontrado una homogeneidad de resultados. Es conveniente mayor investigación sobre el tema, debido a que el SD es considerada la alteración cromosómica más frecuente y la causa principal de DI en el mundo. Objetivo: Conocer la efectividad del CE en comparación con el CM para la remoción de PDB en pacientes mexicanos con SD de entre seis y 14 años. Material y métodos: Estudio transversal experimental, con emparejamiento de sujetos con SD de ambos géneros según la edad (seis a 14 años), asignando el cepillo a utilizar (grupo 1 CM o grupo 2 CE). Se realizó educación dental y método de cepillado con la técnica de Fones, así como control de PDB antes y después el efectuado por medio del índice de O'Leary durante tres días. Se analizaron los resultados utilizando estadística descriptiva e inferencial (prueba de normalidad Lilliefors, prueba t para variables independientes y dependientes). Se aceptó un análisis de significancia p < 0.05. Resultados: La utilización de la t para muestras independientes presentó una mejoría en incremento de dicho marcador de O'Leary en el conjunto total en los tres días de seguimiento respectivamente (t = 6.9, p < 0.00002; t = 8.4, p < 0.00000; y t = 9.5, p < 0.00000). Al comparar por prueba t aplicada a muestras dependientes el índice de O'Leary basal versus cada una de las evaluaciones de seguimiento también se observaron diferencias significativas en los dos conjuntos (grupo 1: p = 0.003, p = 0.0006 y p = 0.0017; grupo 2: p = 0.007, p = 0.0006 y p = 0.0002). Conclusión: La instrucción dental y motivación del paciente fueron determinantes hacia el buen desempeño del cepillado de los dientes y remoción de placa en el par de colectivos, es decir, la reafirmación de la técnica de Fones incrementa gradualmente la mejoría de la forma de uso del cepillo en niños con SD. Ambos métodos con CM y con CE fueron efectivos a fin de remover significativamente la placa, observándose una mayor mejoría en el grupo con CE, sugiriendo que éste disminuye la dificultad de la higiene bucal en personas con SD. Esta línea de investigación es importante en el beneficio de la condición oral de esta población (AU)

Introduction: Oral health in patients having Down syndrome (DS) is a challenge since the changes in motor skills caused by intellectual disability (ID) deteriorate tasks such as the removal of biofilm or dental plaque (DP) with brushing. The effectiveness of electric toothbrushes (ET) compared to manual toothbrushes (MT) in DS patients remains debatable since no homogeneity of results has been found. Further research on the subject is advisable as DS is considered the most frequent chromosomal alteration and the leading cause of ID in the world. Objective: To know the effectiveness of the ET in contrast to the MT for the removal of DP in Mexican DS patients between six and 14 years old. Material and methods: Experimental cross-sectional study, with the pairing of DS subjects of both genders according to age (six to 14 years), assigning the brush to be used (group 1 MT or group 2 ET). Dental education and brushing were performed employing the Fones technique and DP control before and after brushing employing the O'Leary index for three days. The results were analyzed using descriptive and inferential statistics (Lilliefors normality test, t-test for independent and dependent variables). A significance test p < 0.05 was accepted. Results: The t-test for independent samples showed an improvement in the increase of the O'Leary index in the complete group in the three days of follow-up respectively (t = 6.9, p < 0.00002; t = 8.4, p < 0.00000; and t = 9.5, p < 0.00000). When comparing by t-test for dependent samples the baseline O'Leary index versus each of the follow-up evaluations, significant differences were also observed in both groups (group 1: p = 0.003, p = 0.0006 and p = 0.0017; group 2: p = 0.007, p = 0.0006 and p = 0.0002). Conclusion: The dental education and motivation of the patient were decisive for the good performance of tooth brushing and removal of the plaque in both groups. The reaffirmation of the Fones technique gradually increases the improvement of the brushing technique in DS children. Both brushings using MT and ET were effective in removing the biofilm significantly. However, a greater improvement was observed in the group with ET, suggesting that it reduces their difficulty with tooth brushing. This line of research is important to benefit the oral condition of this population (AU)

Retrospective methodology to estimate daily infections from deaths (REMEDID) in COVID-19: the Spain case study.

The number of new daily infections is one of the main parameters to understand the dynamics of an epidemic. During the COVID-19 pandemic in 2020, however, such information has been underestimated. Here, we propose a retrospective methodology to estimate daily infections from daily deaths, because those are usually more accurately documented. Given the incubation period, the time from illness onset to death, and the case fatality ratio, the date of death can be estimated from the date of infection. We apply this idea conversely to estimate infections from deaths. This methodology is applied to Spain and its 19 administrative regions. Our results showed that probable daily infections during the first wave were between 35 and 42 times more than those officially documented on 14 March, when the national government decreed a national lockdown and 9 times more than those documented by the updated version of the official data. The national lockdown had a strong effect on the growth rate of virus transmission, which began to decrease immediately. Finally, the first inferred infection in Spain is about 43 days before the official data were available during the first wave. The current official data show delays of 15-30 days in the first infection relative to the inferred infections in 63% of the regions. In summary, we propose a methodology that allows reinterpretation of official daily infections, improving data accuracy in infection magnitude and dates because it assimilates valuable information from the National Seroprevalence Studies.

Chagas disease screening in pregnant Latin American women: Adherence to a systematic screening protocol in a non-endemic country.

BACKGROUND: Chagas disease (CD) is a chronic parasitic disease caused by Trypanosoma cruzi and is endemic to continental Latin America. In Spain, the main transmission route is congenital. We aimed to assess adherence to regional recommendations of universal screening for CD during pregnancy in Latin American women in the province of Alicante from 2014 to 2018. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective quality study using two data sources: 1) delivery records of Latin American women that gave birth in the 10 public hospitals of Alicante between January 2014 and December 2018; and 2) records of Chagas serologies carried out in those centers between May 2013 and December 2018. There were 3026 deliveries in Latin American women during the study period; 1178 (38.9%) underwent CD serology. Screening adherence ranged from 17.2% to 59.3% in the different health departments and was higher in Bolivian women (48.3%). Twenty-six deliveries (2.2%) had a positive screening; CD was confirmed in 23 (2%) deliveries of 21 women. Bolivians had the highest seroprevalence (21/112; 18.7%), followed by Colombians (1/333; 0.3%) and Ecuadorians (1/348; 0.3%). Of 21 CD-positive women (19 Bolivians, 1 Colombian, 1 Ecuadorian), infection was already known in 12 (57.1%), and 9 (42.9%) had already been treated. Only 1 of the 12 untreated women (8.3%) was treated postpartum. Follow-up started in 20 of the 23 (87.0%) neonates but was completed only in 11 (47.8%); no cases of congenital transmission were detected. Among the 1848 unscreened deliveries, we estimate 43 undiagnosed cases of CD and 1 to 2 undetected cases of congenital transmission. CONCLUSIONS/SIGNIFICANCE: Adherence to recommendations of systematic screening for CD in Latin American pregnant women in Alicante can be improved. Strategies to strengthen treatment of postpartum women and monitoring of exposed newborns are needed. Currently, there may be undetected cases of congenital transmission in our province.

High-throughput drug screening reveals Pyrvinium pamoate as effective candidate against pediatric MLL-rearranged acute myeloid leukemia.

Pediatric MLL-rearranged acute myeloid leukemia (AML) has a generally unfavorable outcome, primarily due to relapse and drug resistance. To overcome these difficulties, new therapeutic agents are urgently needed. Yet, implementing novel drugs for clinical use is a time-consuming, laborious, costly and high-risk process. Therefore, we applied a drug-repositioning strategy by screening drug libraries, comprised of >4000 compounds that are mostly FDA-approved, in a high-throughput format on primary MLL-rearranged AML cells. Here we identified pyrvinium pamoate (pyrvinium) as a novel candidate drug effective against MLL-rearranged AML, eliminating all cell viability at <1000 nM. Additional screening of identified drug hits on non-leukemic bone marrow samples, resulted in a decrease in cell viability of ∼50% at 1000 nM pyrvinium, suggesting a therapeutic window for targeting leukemic cells specifically. Validation of pyrvinium on an extensive panel of AML cell lines and primary AML samples showed comparable viabilities as the drug screen data, with pyrvinium achieving IC50 values of <80 nM in these samples. Remarkably, pyrvinium also induced cell toxicity in primary MLL-AF10+ AML cells, an MLL-rearrangement associated with a poor outcome. While pyrvinium is able to inhibit the Wnt pathway in other diseases, this unlikely explains the efficacy we observed as ß-catenin was not expressed in the AML cells tested. Rather, we show that pyrvinium co-localized with the mitochondrial stain in cells, and hence may act by inhibiting mitochondrial respiration. Overall, this study shows that pyrvinium is highly effective against MLL-rearranged AML in vitro, and therefore represents a novel potential candidate for further studies in MLL-rearranged AML.

Are electrophysiological and oligodendrocyte alterations an element in the development of multiple sclerosis at the same time as or before the immune response?

Efficient communication between the glial cells and neurons is a bi-directional process that is essential for conserving normal functioning in the central nervous system (CNS). Neurons dynamically regulate other brain cells in the healthy brain, yet little is known about the first pathways involving oligodendrocytes and neurons. Oligodendrocytes are the myelin-forming cells in the CNS that are needed for the propagation of action potentials along axons and additionally serve to support neurons by neurotrophic factors (NFTs). In demyelinating diseases, like multiple sclerosis (MS), oligodendrocytes are thought to be the victims. Axonal damage begins early and remains silent for years, and neurological disability develops when a threshold of axonal loss is reached, and the compensatory mechanisms are depleted. Three hypotheses have been proposed to explain axonal damage: 1) the damage is caused by an inflammatory process; 2) there is an excessive accumulation of intra-axonal calcium levels; and, 3) demyelinated axons evolve to a degenerative process resulting from the lack of trophic support provided by myelin or myelin-forming cells. Although MS was traditionally considered to be a white matter disease, the demyelination process also occurs in the cerebral cortex. Recent data supports the notion that initial response is triggered by CNS injury. Thus, the understanding of the role of neuron-glial neurophysiology would help provide us with further explanations. We should take in account the suggestion that MS is in part an autoimmune disease that involves genetic and environmental factors, and the pathological response leads to demyelination, axonal loss and inflammatory infiltrates.