Fetal hemoglobin regulating genetic variants identified in homozygous (HbSS) and heterozygous (HbSA) subjects from South Mexico.

Hemoglobin S is caused by a nucleotide change in HBB gene (HBB:c.20A>T, p.Glu6Val), is presented in diverse forms: simple carriers (HbSA), homozygotes (HbSS) also known as sickle cell anemia, and compound heterozygotes with other ß-hemoglobinopathies. It is worldwide distributed, in Mexico, is frequently observed in the southern states Guerrero, Oaxaca and Chiapas. Elevated fetal hemoglobin (HbF) is associated with mild phenotype; single-nucleotide variants (SNVs) in modifier genes, such as BCL11A, HBG2, HBBP1 pseudogene and HBS1L-MYB intergenic region, upregulate HbF synthesis. The aim of this study was to identify HbF regulating genetic variants in HbSS and HbSA Mexican subjects. We studied 39 individuals (HbSS = 24, 61%, HbSA = 15, 39%) from Chiapas (67%) and Guerrero (33%), peripheral blood was collected in ethylenediamine tetraacetic acid (EDTA) for molecular and hematological studies, DNA was isolated by salting-out technic and genotyping was performed through allelic discrimination by real time polymerase chain reaction (RT-PCR) using Taqman® probes for 15 SNV (in BCL11A: rs6706648, rs7557939, rs4671393, rs11886868, rs766432, rs7599488, rs1427407; HBS1L-MYB: rs28384513, rs7776054, rs9399137, rs4895441, rs9402686, rs1320963; HBG2: rs7482144; and HBBP1: rs10128556). The obtained data were analyzed using IMB SPSS v.22.0 software. All minor alleles were observed in frequencies over 0.05, the most frequent was rs9402686 (0.82), while the less frequent was rs101028556 (0.08). In HbSS group, the mean fetal hemoglobin was 11.9 ± 5.9% and was significantly elevated in BCL11A rs11886868 wildtype homozygotes and in carriers of HBS1L-MYB intergenic region rs7776054 (p = 0.04 and p = 0.03, respectively). In conclusion, in HbSS Mexican patients, two SNVs were observed related to increased HbF; BCL11A rs11886868 and HBS1L-MYB rs7776054.

Sickle cell anemia (SCA) is one of the most common types of hemoglobinopathies in people of African ancestry, it is caused by homozygosity of HbS mutation (HBB:c.20A>T). It is known that fetal hemoglobin plays a key role in decreasing HbS polymerization which damages the erythrocyte structure and is responsible for the characteristic hemolytic crises endured by these patients. Single-nucleotide variant (SNV) in genes that regulate fetal hemoglobin (HbF) after birth have been associated with its increment, thus ameliorating the hematologic phenotype of this pathology and other ß-hemoglobinopathies. Therefore, in this study, we identified, for the first time in Mexican patients with SCA (HbSS) and HbS carriers (HbSA), the presence of 15 SNVs on BCL11A, HBS1L-MYB and HBG2; all HbSS patients had anemia and elevated HbF; 2 variants were related to increased HbF rs11688888C of BCL11A and rs7776054G of HBSIL-MYB; and finally, all minor alleles were found at a frequency higher than 0.05.

IFN-γ mRNA expression is lower in Holstein cows infected with bovine leukemia virus with high proviral load and persistent lymphocytosis.

Bovine leukemia virus (BLV) is a retrovirus that affects primarily milky cows. Animals serologically positive to BLV show a Th1 cytokine profile with a predominance of interferon gamma (IFN-γ). IFN-γ has antiviral activity through mechanisms such as resistance to infection, inhibition of viral replication and apoptosis. The objective of this work was to determine the transcription levels of IFN-γ and its relationship with proviral load and persistent lymphocytosis in a population of Holstein cows of the province of Antioquia, Colombia. IFN-γ transcription levels were evaluated by qPCR in 140 Holstein cows. A one-way analysis of variance and a Student's t test were used to evaluate the differences between the means. The amount of IFN-γ mRNA found in BLV-positive cows was lower than in BLV-negative cows. Moreover, in the group of infected cows a lower level of IFN-γ mRNA expression was found in BLV and persistent lymphocytosis cows (BLV+PL) compared with BLV and aleukemia cows (BLV+AL). The level of IFN-γ mRNA expression was lower in cows with high proviral load (HPL) compared to cows with low proviral load (LPL). BLV infection is related to abnormal expression of IFN-γ mRNA, although IFN-γ has antiviral activity, its expression is affected by high proviral load. Keywords: cytokine; immune system; leukemia; bovine leukemia virus.

Adaptation and validation of the Stanford Presenteeism Scale-6 in healthcare professionals.

AIM: To develop and psychometrically test the Stanford Presenteeism Scale-6 to assess presenteeism in the Spanish healthcare population. BACKGROUND: Presenteeism, referring to going to work despite being ill, has been associated with job stress, productivity losses, reduced patient safety and increased health problems among the professionals who suffer from it. INTRODUCTION: The highest prevalence of presenteeism in the healthcare sector is among nurses. Their decision to attend work while ill has been related to role overload, lack of supervisor support, mental health and physical conditions. METHODS: A cross-sectional and validation study was conducted between September 2015 and June 2016 in a hospital in Asturias, Spain. Four hundred and ninety-five healthcare professionals voluntarily agreed to participate (281 nurses, 122 physicians and 92 nursing assistants). RESULTS: Presenteeism prevalence was high; the majority of it being in the nursing category. Bartlett's test and the Kaiser-Meyer-Olkin test indicated that the data meet the conditions for factorial analysis, evidencing a small variability in the median of each sample item and a significant standard deviation. Adjustment rates obtained in the exploratory factor analysis showed adequacy, and reliability rates also showed adequacy for both factors. It was verified by a confirmatory analysis that the factors of presenteeism are positively associated with burnout. CONCLUSION: The Stanford Presenteeism Scale-6 showed good psychometric properties to study presenteeism in the Spanish healthcare sector. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nursing leaders must develop measurements to assess and control psychosocial risks in order to improve the physical and mental health of professionals and reduce patient safety risks.

Sensitive method for measuring third order nonlinearities in compact dielectric and hybrid plasmonic waveguides.

We demonstrate a sensitive method for the nonlinear optical characterization of micrometer long waveguides, and apply it to typical silicon-on-insulator nanowires and to hybrid plasmonic waveguides. We demonstrate that our method can detect extremely small nonlinear phase shifts, as low as 7.5·10<(-4) rad. The high sensitivity achieved imparts an advantage when investigating the nonlinear behavior of metallic structures as their short propagation distances complicates the task for conventional methods. Our results constitute the first experimental observation of χ((3)) nonlinearities in the hybrid plasmonic platform and is important to test claims of hybrid plasmonic structures as candidates for efficient nonlinear optical devices.

Reproductive traits and number of matings in males and females of Cerambyx welensii (Coleoptera: Cerambycidae) an emergent pest of oaks.

The longhorn beetle Cerambyx welensii is an emerging pest involved in oak decline episodes, whose damage is increasingly reported in dehesa open woodlands. Knowledge of the reproductive biology of C. welensii is a crucial goal due to its new pest status. In this study, we assess the reproductive traits of both sexes in the laboratory (25°C and 60% relative humidity ). In females, body length was 44.9 ± 0.9 mm (mean ± SE), fecundity 132 ± 12 eggs, fertility 70 ± 1 %, longevity 70 ± 3 days, preoviposition period 2 ± 0.2 days, oviposition period 44 ± 3 days and postoviposition period 19 ± 3 days. Fecundity was positively correlated with female size, longevity and oviposition period. Daily fecundity was 3.0 ± 0.2 eggs/day and showed a fluctuating synovigenic pattern with a slight decreasing trend over time. Egg length was 4.24 ± 0.01 mm and egg volume 8.14 ± 0.04 mm3. Egg size was correlated with female size but the relative size of eggs was larger in smaller females. Incubation time was 13.9 ± 0.1 days and hatching did not depend on egg size. Neonate size was positively correlated with egg length. Females were polyandrous (more than 20 lifetime matings) but multiple mating did not increase fecundity, fertility or longevity. In males, body length was 43.7 ± 0.6 mm and longevity 52 ± 3 days. Unlike with females, longevity was positively correlated with male size. Males were polygynous (up to 30 lifetime matings) but mating history did not affect male longevity. Rather to the contrary, long-lived males mated more times because they had more mating chances. Lastly, C. welensii reproductive traits were compared with those other Cerambycidae species and discussed from an adaptive perspective. Our data will be useful to improve management of C. welensii in order to prevent or mitigate its impact in dehesa woodlands and other oak forests.

Acute dietary zinc deficiency before conception compromises oocyte epigenetic programming and disrupts embryonic development.

Recent findings show that zinc is an important factor necessary for regulating the meiotic cell cycle and ovulation. However, the role of zinc in promoting oocyte quality and developmental potential is not known. Using an in vivo model of acute dietary zinc deficiency, we show that feeding a zinc deficient diet (ZDD) for 3-5 days before ovulation (preconception) dramatically disrupts oocyte chromatin methylation and preimplantation development. There was a dramatic decrease in histone H3K4 trimethylation and global DNA methylation in zinc deficient oocytes. Moreover, there was a 3-20 fold increase in transcript abundance of repetitive elements (Iap, Line1, Sineb1, Sineb2), but a decrease in Gdf9, Zp3 and Figla mRNA. Only 53% and 8% of mature eggs reached the 2-cell stage after IVF in animals receiving a 3 and 5 days ZDD, respectively, while a 5 day ZDD in vivo reduced the proportion of 2-cells to 49%. In vivo fertilized 2-cell embryos cultured in vitro formed fewer (38%) blastocysts compared to control embryos (74%). Likewise, fewer blastocyst and expanded blastocyst were collected from the reproductive tract of zinc deficient animals on day 3.5 of pregnancy. This could be due to a decrease in Igf2 and H19 mRNA in ZDD blastocyst. Supplementation with a methyl donor (SAM) during IVM restored histone H3K4me3 and doubled the IVF success rate from 17% to 43% in oocytes from zinc deficient animals. Thus, the terminal period of oocyte development is extremely sensitive to perturbation in dietary zinc availability.

Trajectories of symptom dimensions in short-term response to antipsychotic treatment in patients with a first episode of non-affective psychosis.

BACKGROUND: Trajectory patterns of positive, disorganized and negative dimension symptoms during antipsychotic treatment in drug-naive patients with first-episode psychosis have yet to be examined by using naturalistic data. METHOD: This pragmatic clinical trial randomized 161 drug-naive patients with a first episode of psychosis to olanzapine, risperidone or haloperidol. Patients were assessed with the Scale for the Assessment of Negative Symptoms (SANS) and Positive Symptoms (SAPS) at baseline and at the end of weeks 1, 2, 3, 4 and 6 of antipsychotic treatment. Censored normal models of response trajectories were developed with three dimensions of the SAPS-SANS scores (positive, disorganized and negative) in order to identify the different response trajectories. Diagnosis, cannabis use, duration of untreated psychosis (DUP), smoking and antipsychotic class were examined as possible predictive variables. RESULTS: Patients were classified in five groups according to the positive dimension, three groups according to the disorganized dimension and five groups according to the negative dimension. Longer DUPs and cannabis use were associated with higher scores and poorer responses in the positive dimension. Cannabis use was associated with higher scores and poorer responses in the disorganized dimension. Only schizophrenia diagnosis was associated with higher scores and poorer responses in the negative dimension. CONCLUSIONS: Our results illustrate the heterogeneity of short-term response to antipsychotics in patients with a first episode of psychosis and highlight markedly different patterns of response in the positive, disorganized and negative dimensions. DUP, cannabis use and diagnosis appeared to have a prognostic value in predicting treatment response with different implications for each dimension.

Can valproic acid be an inducer of clozapine metabolism?

INTRODUCTION: Prior clozapine studies indicated no effects, mild inhibition or induction of valproic acid (VPA) on clozapine metabolism. The hypotheses that (i) VPA is a net inducer of clozapine metabolism, and (ii) smoking modifies this inductive effect were tested in a therapeutic drug monitoring study. METHODS: After excluding strong inhibitors and inducers, 353 steady-state total clozapine (clozapine plus norclozapine) concentrations provided by 151 patients were analyzed using a random intercept linear model. RESULTS: VPA appeared to be an inducer of clozapine metabolism since total plasma clozapine concentrations in subjects taking VPA were significantly lower (27% lower; 95% confidence interval, 14-39%) after controlling for confounding variables including smoking (35% lower, 28-56%). DISCUSSION: Prospective studies are needed to definitively establish that VPA may (i) be an inducer of clozapine metabolism when induction prevails over competitive inhibition, and (ii) be an inducer even in smokers who are under the influence of smoking inductive effects on clozapine metabolism.

Oocyte-cumulus cell interactions regulate free intracellular zinc in mouse oocytes.

Zinc increases in the oocyte during maturation and is required for progression and completion of meiosis. The objective of this study was to determine whether cumulus cells regulate the levels of free intracellular zinc in the oocyte during maturation. In the cumulus-oocyte complex (COC) the relative level of free intracellular zinc was almost fourfold higher in cumulus cells compared with the resident germinal vesicle-stage oocyte. Removal of cumulus cells caused a fourfold increase in intracellular zinc in the oocyte by 1 h after cumulus cell removal, but subsequent coculture of denuded oocytes with COC decreased free intracellular zinc in the oocyte by 65%. Thus, cumulus cells suppress free intracellular zinc in the oocyte. The mRNA transcripts for the zinc transporter proteins Slc39a6, Slc39a8, Slc39a9, Slc39a10, Slc39a12, Slc30a2, Slc30a4, Slc30a5 and Slc30a8 mRNAs were higher in oocytes, while Slc39a1, Slc39a7, Slc39a13, Slc39a14, Slc30a6, Slc30a7 and Slc30a9 mRNAs were higher in cumulus cells. Thus a complex zinc transport network is present in the COC. Pretreatment with epidermal growth factor for 4 h abolished the ability of COCs to restrict free intracellular zinc in denuded oocytes. Coculture of denuded metaphase II oocytes with COC lowers free intracellular zinc in mature oocytes. Oocytes matured in vivo or oocytes from older mice had lower levels of free intracellular zinc than oocytes matured in vitro or from younger mice. Thus, a precise mechanism for regulating oocyte zinc homeostasis has been uncovered in the COC that is disrupted with increasing age or by removal of cumulus cells.

Association analysis of vitamin D receptor gene polymorphisms and bone mineral density in postmenopausal Mexican-Mestizo women.

We investigated associations between vitamin D receptor (VDR) gene polymorphisms, FokI T>C (rs2228570), BsmI G>A (rs1544410), ApaI G>T (rs7975232), and TaqI T>C (rs731236), with bone mineral density (BMD) in postmenopausal Mexican-Mestizo women. Three hundred and twenty postmenopausal women participated, who were classified according to World Health Organization criteria as non-osteoporotic (Non-OP; N = 88), osteopenic (Opn; N = 144), and osteoporotic (OP; N = 88). BMD measurements at the lumbar (L1-L4) spine and at the left and right femoral neck were obtained by dual-energy X-ray absorptiometry. Single nucleotide polymorphisms (SNPs) were genotyped using real-time polymerase chain reaction and TaqMan probes. Genotype and allelic frequencies of the 4 VDR SNPs were similar among the 3 groups. Polymorphic allele frequencies were as follows: FokI (C) 0.53, 0.49, 0.56; BsmI (A) 0.26, 0.22, 0.23; ApaI (T) 0.43, 0.39, 0.44; TaqI (C) 0.27, 0.22, 0.23 for the Non-OP, Opn, and OP groups, respectively. Although no associations were found between the SNPs and BMD, based on the putative function of the FokI SNP, we constructed, for the first time, the haplotype with the 4 VDR SNPs, and found that the CGGT haplotype differed between the Non- OP and OP groups (21.8 vs 31.8%, P < 0.05). The risk analysis for this haplotype was nearly significant under the dominant model (OR = 1.783, 95%CI = 0.98-3.25, P = 0.058). This result suggests a possible susceptibility effect of the C allele of the FokI SNP for the development of osteoporosis in postmenopausal Mexican-Mestizo women.

Phylogenetic analysis of the partial sequences of the env and tax BLV genes reveals the presence of genotypes 1 and 3 in dairy herds of Antioquia, Colombia.

Bovine leukemia virus (BLV) is a retrovirus that primarily infects dairy cows. Although few studies have also used the tax gene, phylogenetic studies of BLV use mostly the env gene. The aim of this work was to establish the circulating genotypes of BLV in specialized dairy cattle from Antioquia, Colombia. Twenty blood samples from Holstein Friesian cows were collected, and their DNA was isolated. A PCR was performed for a partial region of the env and tax genes. A phylogenetic analysis was carried out using the maximum likelihood and Bayesian methods for both genes. Nineteen sequences were identified as genotype 1 by env and tax genes. Only one sequence was clustered with genotype 3 and had the highest proportion of different nucleotide sites compared to other strains. Four amino acid substitutions in the 134 amino acid residue fragment of the Env protein were identified in the Colombian sequences, and three new amino acid substitutions were reported in the 296 amino acid residue fragment of the Tax protein. R43K (Z finger), A185T (Activation domain), and L105F changes were identified in the genotype 3 sample. This genotype has been reported in the United States, Japan, Korea, and Mexico, but so far, not in Colombia. The country has a high rate of imported live animals, semen, and embryos, especially from the United States. Although it is necessary to evaluate samples from other regions of the country, the current results indicate the presence of two BLV genotypes in specialized dairy herds.

Common surgical training program: standardization of learning quality. / Programa de formación quirúrgica común: uniformidad en la calidad del aprendizaje.

INTRODUCTION: The various surgical specialties in our center have used the simulation and experimental surgery resources available for their training tasks in minimally invasive surgery (MIS) in an individualized manner. With this learning model, a great dispersion of effort and expense was observed, so it was decided to create a unified program based on the following: shared learning, synergy among specialties, moderation of the economic cost, and rational use of the facilities. OBJECTIVE: To describe and assess our consensually designed training program in order to consolidate a shared learning strategy that will enable our residents to acquire and perfect surgical skills in MIS. MATERIALS AND METHODS: The program consists of various increasingly complex phases implemented on a continuous basis throughout the period of specialized training in the virtual laboratory and experimental operating room. The assessment methods were based on quantifiable criteria: percentage of efficiency and completion time of the "McGill Inanimate System for Training and Evaluation of Laparoscopic Skills" (MISTELS) exercises at the beginning and end of the program. An economic study was also conducted. RESULTS: 20 residents have completed the program. Mean times show a significant reduction in each of the exercises. The efficiency percentages at the end of the program were higher than at the beginning (p < 0.001). The cost of the program represented a saving of 67.89%. CONCLUSION: The new MIS training program improved the quality of learning in a safe environment, establishing common criteria among the different specialties and an improved use of resources.

INTRODUCCION: Las diferentes especialidades quirúrgicas de nuestro centro han usado los recursos de simulación y cirugía experimental para sus tareas de formación en cirugía mínimamente invasiva (CMI) de manera individualizada. Con este modelo de aprendizaje se detectó una gran dispersión de esfuerzos y gasto, por lo que se decidió crear un programa unificado basado en: aprendizaje compartido, sinergia entre especialidades, moderación del coste económico y uso racional de las instalaciones. OBJETIVO: Describir y evaluar nuestro programa de entrenamiento diseñado por consenso de cara a la consolidación de una estrategia de aprendizaje compartido que permita a nuestros residentes adquirir y perfeccionar habilidades quirúrgicas en CMI. MATERIAL Y METODOS: El programa consta de diferentes fases con complejidad creciente desarrolladas durante todo el periodo de formación especializada de forma continuada en laboratorio virtual y quirófano experimental. Los criterios de evaluación se basaron en criterios cuantificables: porcentaje de eficiencia y tiempo de realización de los ejercicios de McGill Inanimate System for Training and Evaluation of Laparoscopic Skills (MISTELS) al inicio y final del programa. Se realizó también el estudio económico. RESULTADOS: Han completado el programa 20 residentes. Los tiempos medios demuestran una reducción significativa en cada uno de los ejercicios. Los porcentajes de eficiencia al final fueron mayores que al inicio del programa (p < 0,001). El coste del programa supuso un ahorro del 67,89%. CONCLUSION: El nuevo programa de entrenamiento en CMI mejoró la calidad de aprendizaje en un entorno seguro, estableciendo criterios comunes entre las diferentes especialidades y un mayor aprovechamiento de los recursos.

External validation and applicability of the EORTC risk tables for non-muscle-invasive bladder cancer.

PURPOSE: To perform an external validation of the EORTC risk tables and to evaluate their applicability in the patients of our institution by comparing the actual risk of recurrence and progression in our series to those obtained through the application of the EORTC tables. METHODS: Retrospective study, based on a prospective cohort of 417 patients in follow-up with primary TaT1 bladder tumors, operated on in our center between 1998 and 2008 and collected in our database. Risk scores were assigned depending on the tumor characteristics to divide our series into four risk groups according to these ratings. An analysis of survival was carried out to calculate the probability of recurrence by the method of Kaplan-Meier. RESULTS: A total of 417 patients with a median follow-up of 59 months were studied. The overall recurrence and progression rates of our series were 25.95% (21.97-30.49) and 4.86% (3.16-7.43) at 1 year and 53.46% (48.06-59.05) and 8.43% (5.95-11.86) at 5 years, respectively. When we compare our rates of recurrence and progression by groups with the corresponding values from Sylvester's publication, an overlapping of the confidence intervals between both populations is detected. CONCLUSIONS: In terms of the applicability of the EORTC risk tables in our patients' population, we conclude that these tables predict accurately the clinical course of patients with NMIBC. Due to the sample size of our study, we can only validate the recurrence model of the EORTC tables.

[From in-person didactic sessions to videoconferencing during the COVID-19 pandemic: satisfaction survey among participants]. / Cambio de sesiones docentes presenciales a virtuales durante la pandemia de COVID-19 en un servicio de neurología: descripción del proceso y satisfacción de los usuarios.

INTRODUCTION AND AIM: COVID-19 pandemic has disturbed many hospital activities, including medical education. We describe the switch from in-person didactic sessions to videoconferencing in a Neurology department. We analyse the opinions and satisfaction of participants. MATERIAL AND METHODS: Narrative description of the adopted measures; Online survey among participants. RESULTS: One of the three weekly sessions was cancelled, and two switched to videoconferencing. There were more participants online than in the conference hall. 49 users answered the survey, 51% women, mean age 40.5 years (range 25-65). Satisfaction was higher for previous face-to-face meetings (8.68) than for videoconferencing (8.12) (p=0.006). There was a significant inverse correlation between age and satisfaction with virtual sessions (r=-0.37; p=0.01), that was not found for in-person attendance. Most users (75.5%) would prefer to continue with online sessions when the pandemic is over, and 87.8% support inter-hospital remote meetings, but the safety of web platforms is a concern (53.1%). CONCLUSIONS: The change from in-person to virtual sessions is an easy measure to implement in a neurology department, with a good degree of satisfaction among users. There are some unsolved problems with the use of commercial web platforms and inter-hospital connection. Most users recommend leadership and support from educational and health authorities.

TITLE: Cambio de sesiones docentes presenciales a virtuales durante la pandemia de COVID-19 en un servicio de neurología: descripción del proceso y satisfacción de los usuarios.Introducción y objetivo. La pandemia de COVID-19 ha trastornado la actividad hospitalaria, incluyendo la docente. Se describe el cambio de un sistema presencial a otro de sesiones en línea en un servicio de neurología, y se analizan la satisfacción y las opiniones de los usuarios. Material y métodos. Exposición de las medidas adoptadas para pasar a modalidad en línea y análisis de una encuesta entre los participantes. Resultados. Se pasó de tres a dos sesiones semanales, con restricción del público presencial. El público virtual superó al presencial. Contestaron la encuesta 49 participantes, un 51% mujeres, con una media de 40,5 años (rango: 25-65). La satisfacción de los asistentes fue mayor para las sesiones presenciales (8,68) que para las en línea (8,12) (p = 0,006). Existía una correlación inversa significativa entre la edad y la satisfacción con las sesiones en línea (r = ­0,37; p = 0,01) que no se daba para las sesiones presenciales. El 75,5% fue partidario de mantener las sesiones virtuales cuando se eliminaran las restricciones de aforo. Una mayoría (87,8%) apoyó sesiones interhospitalarias y recomienda que las autoridades sanitarias faciliten aplicaciones informáticas seguras (53,1%). Conclusiones. La introducción de sesiones virtuales es una medida fácil de implementar en un servicio de neurología, con un alto grado de satisfacción de los usuarios, aunque menor que con las sesiones presenciales. Existen problemas no resueltos respecto al uso de plataformas comerciales y conexión interhospitalaria. Sería recomendable que las autoridades sanitarias y educativas desarrollaran aplicaciones seguras y fomentaran la educación médica en línea.

Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms.

SARS-CoV-2 infection can associate diverse neurological manifestations. Several studies have provided proof to support the theory of neurotropic involvement of SARS-CoV-2. Alpha-synuclein has been described as a native antiviral factor within neurons, and upregulation of this protein can be seen in animals that suffered other neuroinvasive infections. To assess if increased expression of this protein takes place in COVID-19 patients with neurological symptoms, we analyzed serum total alpha-synuclein levels in three groups: seven COVID-19 patients with myoclonus, Parkinsonism and/or encephalopathy; thirteen age- and sex-matched COVID-19 patients without neurological involvement and eight age- and sex-matched healthy controls. We did not find differences among them. In a subset of four patients, the change in serum alpha-synuclein before and after the onset of neurological symptoms was not significant either. Cerebrospinal fluid alpha-synuclein levels were also similar between neurological COVID-19 and healthy controls. Overall, these results cannot support the hypothesis of alpha-synuclein upregulation in humans with neurological symptoms in COVID-19. Further research taking into account a larger group of COVID-19 patients including the whole spectrum of neurological manifestations and disease severity is needed.

Pharmacologic management of patients with hepatic and pancreatic diseases that involve immunosuppressive therapies. Position statement within the framework of the SARS-CoV-2 (COVID-19) pandemic. / Manejo farmacológico de pacientes con enfermedades hepáticas y pancreáticas que involucran terapias inmunosupresoras. Posicionamiento en el marco de la pandemia de SARS-CoV-2 (COVID-19).

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus2 (SARS-CoV-2) virus. COVID-19 affected more than 6million persons worldwide in fewer than 4 months, after the report of the first cases in China in December 2019. The relation of the disease caused by SARS-Cov-2 to immunosuppressive treatment used in different gastrointestinal disorders is uncertain, resulting in debate with regard to suspending immunosuppressive therapy to improve infection outcome. Said suspension implies the inherent risk for graft rejection or autoimmune disease exacerbation that can potentially worsen the course of the infection. Based on the presently available evidence, a treatment stance has been established for patients with gastrointestinal diseases that require immunosuppressive therapy.

Comparison of 3 Explant-Based Prognostic Models as Predictors of Hepatocellular Carcinoma Recurrence After Liver Transplantation: Analysis of Our Experience.

Tumor load is often underdiagnosed on radiological examination previous to liver transplantation (LT) for hepatocarcinoma (CHC). Thus, post-liver transplant explant analysis is required following transplantation to assess the risk of the recurrence of CHC. The objectives were to compare the characteristics of CHC on pre-LT radiological examination and explant histology and validate three models for the prediction of recurrence based on data from a cohort of patients treated in our hospital. METHODS: A retrospective study was undertaken of 105 LTs for CHC performed in our unit between January 2006 and January 2015. The minimum follow-up was five years. The preoperative radiological tumor stage was compared to the explant-based histologic stage. Three prognostic models were validated using our cohort of patients. RESULTS: Following Milan's criteria, the tumor load was underdiagnosed on pre-LT radiological examination in 20 patients, which accounted for 19% of the total sample. The 5-year overall recurrence was 6.6% for scores <4 and 33.3% for scores ≥4 according to Decaens' model; 7% for scores ≤7 and 25% for scores >7 in the Up-to-Seven model; and 3.6% for PCRS ≤0, 27.8% for PCRS1-2, and 100% for PCRS≥3 according to Chan's model. The predictive model for 5-year recurrence after LT with the greatest area under the curve was Chan's model (0.813 [95% CI: 0.650-0.977]) versus Decaens' model (0.674 [95% CI: 0.483-0.866]) and the Up-to-Seven model (0.481 [95% CI: 0.296-0.667]). CONCLUSIONS: A pre-LT radiological examination leads to the underdiagnosis of tumor load, and the risk for recurrence must be recalculated following LT. In light of the results obtained, Chan's model is more accurate in predicting 5-year recurrence of CHC post-LT based on 3 levels of risk. New prognostic models are needed to optimize the prediction of recurrence after liver transplantation for hepatocarcinoma.

[Cavernous sinus syndrome as the initial symptom of Burkitt's lymphoma: a case report and literature review]. / Sindrome del seno cavernoso como inicio de un linfoma de Burkitt: a proposito de un caso y revision de la bibliografia.

INTRODUCTION: The cavernous sinus is a structure in the base of the skull that houses several nerve and vascular structures. Its compromise leads to cavernous sinus syndrome, which is a combination of oculomotor disorders and others affecting the first two trigeminal branches, often accompanied by pain or proptosis. Infiltration due to Burkitt's lymphoma is a rare cause of this syndrome. CASE REPORT: A 43-year-old male, carrier of human immunodeficiency virus, with good control of the disease, who developed a clinical picture consisting of progressive painful ophthalmoplegia in the presence of a laterocervical adenopathy. Complementary tests allowed a diagnosis of Burkitt's lymphoma with extranodal extension to the cavernous sinus. A review of the cases published in Medline was also carried out: a total of 15 cases were detected and their epidemiological characteristics, form of presentation, extracranial involvement at the time of diagnosis and clinical progression were described. CONCLUSIONS: Burkitt's lymphoma is a high-grade lymphoproliferative syndrome. Its form associated with immunodeficiency is an important cause of morbidity and mortality in this subgroup of patients. In the cases analysed in the literature, the age of presentation varied and the form of onset was a progressive painful ophthalmoplegia or numb chin syndrome. Exclusive involvement of the cavernous sinus was infrequent, but in that case it entailed a poor prognosis. It is important to rule out a primary extracranial origin and not to confuse it with an idiopathic Tolosa-Hunt syndrome that would delay the beginning of antitumour treatment.

TITLE: Sindrome del seno cavernoso como inicio de un linfoma de Burkitt: a proposito de un caso y revision de la bibliografia.Introduccion. El seno cavernoso es una estructura de la base craneal que alberga varias estructuras nerviosas y vasculares. De su afectacion se deriva el sindrome del seno cavernoso, una combinacion de alteraciones oculomotoras y de las dos primeras ramas del trigemino, frecuentemente acompañadas de dolor o proptosis. La infiltracion por un linfoma de Burkitt es una causa infrecuente de este sindrome. Caso clinico. Varon de 43 años, portador del virus de la inmunodeficiencia humana, con buen control de la enfermedad, que desarrolla un cuadro consistente en oftalmoplejia dolorosa progresiva en presencia de adenopatia laterocervical. Las pruebas complementarias permiten el diagnostico de linfoma de Burkitt con extension extranodal al seno cavernoso. Tambien se realiza una revision de los casos publicados en Medline: se recogen un total de 15 casos y se describen sus caracteristicas epidemiologicas, forma de presentacion, afectacion extracraneal en el momento del diagnostico y evolucion clinica. Conclusiones. El linfoma de Burkitt es un sindrome linfoproliferativo de alto grado. Su forma asociada a inmunodeficiencia es una importante causa de morbimortalidad en este subgrupo de pacientes. En los casos analizados en la bibliografia, la edad de presentacion fue variable y la forma de inicio fue una oftalmoplejia dolorosa progresiva o un sindrome de numb chin. Fue infrecuente una afectacion exclusiva del seno cavernoso, pero en ese caso conllevaba un mal pronostico. Es importante descartar un origen primario extracraneal y no confundirlo con un sindrome de Tolosa-Hunt idiopatico que retrasaria el inicio del tratamiento antitumoral.

Donation After Cardiac Death in Liver Transplantation: An Additional Source of Organs With Similar Results to Donation After Brain Death.

BACKGROUND: As new sources of organs are needed, liver transplantation using donors after cardiac death (DCD) is progressively increasing, but outcomes with this method are still questioned. This study was accomplished to verify that DCD outcomes are comparable to those seen in donation after brain death (DBD). METHODS: This was a prospective cohort study including 100 liver transplantation performed between 2014 and 2017, divided according to donor type in 75 DBD and 25 DCD. RESULTS: DCD donors were younger (mean age: DCD 56 years, DBD 59 years; P = .009). Mean Modified End-stage Liver Disease (MELD) score was lower for DCD (DCD 16, DBD 19; P < .001). No differences were found regarding ischemia times and development of postreperfusion syndrome or coagulopathy. Primary graft dysfunction was more frequent in DCD (60%, DCD 29.3%; P = .006). Rates of primary graft nonfunction (DCD 0%, DBD 1.3%; P = .562) and acute rejection (DCD 20%, DBD 16.4%; P = .685) were similar. Acute kidney injury occurred more often in DBD (DCD 32%, DBD 12%; P = .051). Length of stay was comparable. Rates of biliary complications (DCD 20%, DBD 26.7%; P = .505) were similar, unlike ischemic cholangiopathy (DCD 12%, DBD 1.3%; P = .018). Retransplantation rates were also similar (DCD 8%, DBD 4%; P = .427) as was survival rate after 3 years (DCD 84%, DBD 86.7%; P = .739). CONCLUSION: DCD represents an additional graft source with results that are encouraging and may be comparable to DBD with a careful donor and recipient selection.

Detection of spinal cord compression in dogs with cervical intervertebral disc disease by magnetic resonance imaging.

The medical records and magnetic resonance images of 33 dogs with surgically confirmed Hansen type I cervical intervertebral disc disease were reviewed. Fourteen of the dogs were chondrodystrophic and 19 were not chondrodystrophic. The most common clinical sign was neck pain, which affected 28 of the dogs, and 23 of the dogs were able to walk. Fifteen of the dogs had developed clinical signs acutely, within the previous 24 hours. On cross-sectional images the median area of spinal cord compression was 26 per cent (range 11 to 71 per cent) of the normal spinal cord area. The degree of spinal cord compression was significantly associated with the dogs' presurgical neurological status but not with their postsurgical neurological status. The dogs with an acute onset of clinical signs had more severe neurological dysfunction before surgery, but their condition improved more as a result of surgery.