Fishing the Targets of Bioactive Compounds from Psidium guajava L. Leaves in the Context of Diabetes.

Psidium guajava L. (guava) leaves have demonstrated their in vitro and in vivo effect against diabetes mellitus (DM). However, there is a lack of literature concerning the effect of the individual phenolic compounds present in the leaves in DM disease. The aim of the present work was to identify the individual compounds in Spanish guava leaves and their potential contribution to the observed anti-diabetic effect. Seventy-three phenolic compounds were identified from an 80% ethanol extract of guava leaves by high performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry. The potential anti-diabetic activity of each compound was evaluated with the DIA-DB web server that uses a docking and molecular shape similarity approach. The DIA-DB web server revealed that aldose reductase was the target protein with heterogeneous affinity for compounds naringenin, avicularin, guaijaverin, quercetin, ellagic acid, morin, catechin and guavinoside C. Naringenin exhibited the highest number of interactions with target proteins dipeptidyl peptidase-4, hydroxysteroid 11-beta dehydrogenase 1, aldose reductase and peroxisome proliferator-activated receptor. Compounds catechin, quercetin and naringenin displayed similarities with the known antidiabetic drug tolrestat. In conclusion, the computational workflow showed that guava leaves contain several compounds acting in the DM mechanism by interacting with specific DM protein targets.

Effect of Pulsed Light on Quality of Shelled Walnuts.

Shelled walnuts are considered a microbiologically low-risk food but have been linked to some outbreaks, and a treatment aiming to decrease this risk is desirable. Pulsed light (PL) may be an alternative, providing it does not seriously impair their quality. This work assessed the impact of PL on some quality attributes of walnuts. To do this, measurements of rancidity, volatiles, total phenols, antioxidant activity, and descriptive sensory analysis were carried out on untreated and PL (43 J/cm2)-treated kernels. PL had no statistically significant (p > 0.05) effects on TBARS, peroxide value, total phenols, and antioxidant activity but significantly increased the concentration of volatiles related to green/herbaceous odors and decreased compounds related to fruity and citrus odors. The descriptors nut overall, walnut odor and flavor, and aftertaste were given statistically significantly (p < 0.05) higher scores, while descriptors woody odor and sweet received lower scores; 16 other traits such as all those related to color, texture, and rancidity were unaffected. No significant (p > 0.05) effects on total phenols and antioxidant activity in general were observed during the course of PL treatment. It can be concluded that PL technology may be used in shelled walnuts with only mild effects on their quality; a storage study must be carried out in order to determine the effect of PL treatment on its shelf-life.

Lactate-dehydrogenase associated with mortality in hospitalized patients with COVID-19 in Mexico: a multi-centre retrospective cohort study.

INTRODUCTION AND OBJECTIVES: As of January 2021, over 88 million people have been infected with COVID-19. Almost two million people have died of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A high SOFA score and a D-Dimer >1 µg/mL identifies patients with high risk of mortality. High lactate dehydrogenase (LDH) levels on admission are associated with severity and mortality. Different degrees of alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) abnormalities have been reported in these patients, its association with a mortality risk remains controversial. The aim of this study was to explore the correlation between LDH and in-hospital mortality in Mexican patients admitted with COVID-19. MATERIALS & METHODS: We performed a retrospective multi-centre cohort study with 377 hospitalized patients with confirmed SARS-CoV-2 in three centres in Mexico City, Mexico, who were ≥18 years old and died or were discharged between April 1 and May 31, 2020. RESULTS: A total of 377 patients were evaluated, 298 (79.1%) patients were discharged, and 79 (20.9%) patients died during hospitalization. Non-survivors were older, with a median age of 46.7 ± 25.7 years old, most patients were male. An ALT > 61 U/l (OR 3.45, 95% CI 1.27-9.37; p = 0.015), C-reactive protein (CRP) > 231 mg/l (OR 4.71, 95% CI 2.35-9.46; p = 0.000), LDH > 561 U/l (OR 3.03, 95% CI 1.40-6.55; p = 0.005) were associated with higher odds for in-hospital death. CONCLUSIONS: Our results indicate that higher levels of LDH, CRP, and ALT are associated with higher in-hospital mortality risk in Mexican patients admitted with COVID-19.

Corrigendum: Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

This corrects the article DOI: 10.1038/ajg.2016.439.

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.

OBJECTIVES: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. METHODS: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. RESULTS: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. CONCLUSIONS: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.

Adverse reactions and tolerability of high-dose sublingual allergen immunotherapy.

BACKGROUND: Sublingual allergen immunotherapy is an effective treatment against allergic respiratory disease. Many studies have shown the safety of this type of therapy, although the factors that might affect the tolerability of high-dose sublingual immunotherapy have not been well established. The aim of this study was to determine the factors that affect the tolerability of sublingual allergen immunotherapy. PATIENTS AND METHODS: A total of 183 subjects aged ≥5 years, diagnosed with allergic rhinitis with/without mild to moderate asthma due to sensitization to grass, olive pollen, or mites, were included in this open, retrospective, multicentric, noninterventional study. Sublingual immunotherapy was administered for at least 3 months. RESULTS: The most frequent adverse reaction was oral pruritus (13.7% of the patients). Most of the reactions were local (84.7%) and immediate (93.5%) and occurred during the initiation phase (60.6%). All reactions were mild to moderate in severity. No serious adverse reactions were registered. When comparing factors with potential influence on the occurrence of adverse reactions, the results between the groups of subjects with and without adverse reactions showed no statistically significant differences in sex (P=0.6417), age (P=0.1801), years since the disease was first diagnosed (P=0.3800), treatment composition (P=0.6946), polysensitization (P=0.1730), or clinical diagnosis (P=0.3354). However, it was found that treatment duration had a statistically significant influence (3 months, >3 months: P=0.0442) and the presence of asthma was close to statistical significance (P=0.0847). CONCLUSION: In our study, treatment duration is significantly associated with the occurrence of adverse reactions after the administration of high doses of sublingual allergen immunotherapy.

Genotype frequencies of VKORC1 and CYP2C9 in native and Mestizo populations from Mexico, potential impact for coumarin dosing.

The collection of pharmacogenetic variants in Mexican populations remains incomplete, thus, we aimed to characterize the genotype frequency of 11 SNP on CYP2C9 and VKORC1 in more than one-thousand individuals, and to explore their potential impact on coumarin dosing. In natives, genotype frequencies indicate that over 92% would reflect an extensive metabolism. For Mestizo populations, the proportion of CYP2C9 extensive (79%), intermediate (20.0%) and poor metabolizers (1.0%) was significantly different from that of natives, and varied among the different states of Mexico. Genotype frequencies of 7 SNP on VKORC1, were more homogenously distributed among natives and Mestizos. VKORC1 haplotype analysis revealed that most natives can be grouped into haplotypes H1 or H7-H8, while Mestizos showed a wider frequency distribution for other haplotypes. Our observations confirm previous reports on the genotype distribution of major CYP2C9 alleles, and contribute to the collection of genotype frequencies on relevant VKORC1 variants.

Pharmacogenetics and rational drug use around the world.

The WHO embraces evidence-based medicine to formulate an essential medicines list (EML) considering disease prevalence, drug efficacy, drug safety and cost-effectiveness. The EML is used by developing countries to build a national formulary. As pharmacogenetics in developed countries evolves, the Pharmacogenetics for Every Nation Initiative (PGENI) convened with representatives from China, Mexico, Ghana and South Africa in August 2009 to evaluate the use of human pharmacogenetics to enhance global drug use policy. The diseases causing mortality, the lack of integration of pharmacovigilance at the national formulary level, the pharmacogenetics research agenda and pharmacogenetics clinician education did not differ greatly among the countries. While there are many unanswered questions, systematically incorporating pharmacogenetics at the national formulary level promises to improve global drug use.

Comparing meta-analyses for chronic obstructive pulmonary disease.

Evaluation of: Oppe M, Al M, Rutten-van Mölken M. Comparing methods of data synthesis. Re-estimating parameters of an existing probabilistic cost-effectiveness model. Pharmacoeconomics 29(3), 239-250 (2011). In the paper by Oppe et al., a cost-effectiveness analysis of alternative treatments for chronic obstructive pulmonary disease (COPD), based on data from four different trials, is considered. The goal is to compare the usual (frequentist and Bayesian) fixed-effects (FE) and random-effects (RE) normal model for carrying out meta-analysis. Under RE and FE models, the meta-estimation of some quantities of interest for the disease are also carried out using three out of the four trials, and afterwards data from the fourth are incorporated into the meta-estimation. From these sequential estimators, some conclusions on the FE and RE procedures are drawn. Furthermore, as far as the cost-effectiveness is concerned, the main conclusion of the paper is that the Bayesian RE procedure overrides the Bayesian FE and frequentist methods for cost-effectiveness meta-analysis.

Association of the genetic marker for abacavir hypersensitivity HLA-B*5701 with HCP5 rs2395029 in Mexican Mestizos.

UNLABELLED: Prospective screening for HLA-B*5701 decreases or abolishes abacavir hypersensitivity reaction. In Caucasians, the HLA complex protein 5 gene (HCP5) rs2395029(G) allele is in complete linkage disequilibrium (LD) with HLA-B*5701 (r(2) = 1). AIM: To assess the frequency of HLA-B*5701 and its LD with HCP5 rs2395029(G) allele, to extend our knowledge of genetic variants that are of critical relevance for the development of pharmacogenetics in Mexico. MATERIALS & METHODS: We genotyped 300 Mexican Mestizos from the Mexican Genome Diversity Project. HLA-B*5701 genotyping was performed using a DNA sequencing method. HCP5 rs2395029 was genotyped using a custom TaqMan(®) SNP genotyping assay and confirmed by direct sequencing. Genotypes for 14 SNPs in the HCP5 region were retrieved from the Mexican Genome Diversity Project database for LD analysis. RESULTS: HLA-B*5701 carrier frequency was 2% and the allelic frequency was 0.010. Haplotype analysis revealed that HLA-B*5701 and the HCP5 rs2395029(G) allele are in complete LD (r(2) = 1) in this Mexican Mestizos sample. CONCLUSION: It is feasible to have a pharmacogenetic program based on HCP5 rs2395029 genotyping as a screening tool with confirmation of HLA-B*5701 carriage by sequenciation, to prevent abacavir hypersensitivity reaction in Mexican patients before initiating abacavir therapy.

Bayesian variable selection in cost-effectiveness analysis.

Linear regression models are often used to represent the cost and effectiveness of medical treatment. The covariates used may include sociodemographic variables, such as age, gender or race; clinical variables, such as initial health status, years of treatment or the existence of concomitant illnesses; and a binary variable indicating the treatment received. However, most studies estimate only one model, which usually includes all the covariates. This procedure ignores the question of uncertainty in model selection. In this paper, we examine four alternative Bayesian variable selection methods that have been proposed. In this analysis, we estimate the inclusion probability of each covariate in the real model conditional on the data. Variable selection can be useful for estimating incremental effectiveness and incremental cost, through Bayesian model averaging, as well as for subgroup analysis.

Reduction of blood loss from laboratory testing in hospitalized adult patients using small-volume (pediatric) tubes.

CONTEXT: Blood loss from laboratory testing (BLLT) can be significant in hospitalized patients. It is a common practice to draw full large-volume tubes of blood from adults. OBJECTIVE: To determine whether BLLT occurred when a small-volume (pediatric) blood collection tube (SVT) was substituted for each large-volume blood collection tube and to note whether an adequate sample still was obtained. DESIGN: During 2 consecutive weeks, hospital test requisitions were reviewed to collect patient demographics, tests requested, and number and type of tubes obtained. The amount of blood collected and BLLT per patient were calculated. Reduced sample requirements were calculated, and phlebotomists and ward nurses were required to use SVTs. After 2 weeks of familiarization, data were collected as previously described. Laboratory technicians logged problems related to the use of SVTs. RESULTS: Baseline: 227 patients had 664 requisitions, and median BLLT per patient was 13.5 mL (interquartile range [IQR], 7.6-27.3 mL). In critical care patients, the median was 19.9 mL (IQR, 12.0-35.8 mL), and maximum BLLT was 159.8 mL. Intervention phase: 246 patients had 696 requisitions, median BLLT was 3.7 mL (IQR, 1.2-6.3 mL; P < .001). In critical care patients, the median was 5.1 mL (IQR, 2.3-10.9 mL), and maximum BLLT was 61.8 mL (P < .001). All tests requested could be performed using SVTs, and no additional blood collections were required. Use of SVTs reduced overall BLLT per patient by 73% and by 74% in critical care patients. CONCLUSIONS: By decreasing the size of the blood collection tube for adults, we were able to markedly reduce BLLT without noting any insufficient specimen volumes.

Dopamine D4 receptors are heterogeneously distributed in the striosomes/matrix compartments of the striatum.

Two important aspects of striatal function, exploratory behaviour and motor co-ordination, require the integrity of the dopamine D4 receptor subtype. These receptors are also implicated in the pathophysiology of certain neuropsychiatric disorders. However, the distribution of D4 receptors in the striatum has not yet been described and this situation impairs our understanding of the anatomical substrate in which D4 receptors function. We developed a D4 receptor-specific antibody that has permitted us to investigate the regional and cellular localization of the receptor in the neostriatum of the rat, mouse, cat and monkey. The subcellular distribution and the synaptic organization of this receptor were also determined in the rat striatum. We found moderate levels of D4 receptor expression in the caudoputamen and lower levels in the nucleus accumbens. These receptors were expressed in cell bodies and in the neuropil and were heterogeneously distributed among different striatal compartments, being more abundant in striosomes than in the matrix. At the subcellular level, the receptor immunoreactivity was mainly localized to dendritic shafts and spines. The prominent immunoreactivity observed in the striosomes indicates that integrative processes involved in D4-mediated limbic behaviours occurs through the striosomes rather than accumbens, whereas the motor behaviour is based in the striatal matrix.

Reacción hemolítica transfusional tardía por anti-Kpb (KEL4). Reporte del primer caso de anti-Kpb en la República Mexicana / Delayed hemolytic transfusion reaction by anti Kbp (Kel4). Report of the first case of anti-Kpb in Mexico

Se reportan los datos clínicos y de laboratorio de un paciente que presentó reacción hemolítica transfusional tardía causada por un anti-Kbp que no era detectable en las pruebas de compatibilidad pretransfusional, y una segunda reacción hemolítica aguda cansada por la transfusión de una unidad de concentrado de eritrocitos erróneamente identificada como compatible. Fue necesaria la participación de un laboratorio nacional de referencia norteamericano y del archivo de donadores de fenotipos raros para el manejo de esta paciente. Este caso se presenta por la muy baja frecuencia de este anticuerpo, siendo la primera ocasión en la que se identifica la especificidad anti-Kpb en la República Mexicana

Criterios para el uso terapéutico de los componentes sanguíneos / The guidelines for therapeutic use of blood components

La percepción de la comunidad médica y del público en general de la seguridad de la transfusión sanguínea cambió radicalmente con la aparición del Síndrome de Inmunodeficiencia Adquirida. Con objeto de hacer un uso racional de la hemoterapia y evitar la exposición del paciente a riesgos innecesarios, se han desarrollado lineamientos para guiar el uso terapéutico de la sangre. El objetivo de éste artículo es presentar los lineamientos actuales para cada uno de los componentes sanguíneos. Su intención es asistir a los médicos en la selección del producto correcto de acuerdo a las necesidades del paciente. Sirven como marco de referencia desarrollado por grupos de expertos, los cuales pueden y deben ser adaptados a la práctica de cada hospital a través de un consenso entre el Banco de Sangre y los servicios que con mayor frecuencia utilizan sus servicios