Hypogammaglobulinemia Class G Is Present in Compensated and Decompensated Patients with Propionate Defects, Independent of Their Nutritional Status.

Propionate defects (PDs) mainly include methylmalonic (MMA) and propionic acidemia (PA) defects. Lifelong PD patients progress from the compensated to the decompensated stages, the latter of which are characterized by life-threatening acidemia and hyperammonemia crises. PD patients can suffer immunocompromise, especially during the decompensation stage. There is a significant gap in the research regarding the humoral immune response in PD patients. Here, we analyzed serum immunoglobulin concentrations and hemograms across compensated and decompensated stages in PD patients. Nutritional status and crisis triggers of decompensation were also explored. Twenty patients were studied, and 25 decompensation events (DE) and 8 compensation events (CE) were recorded. Compared with those in the CE group, the IgG levels in the DE group (513.4 ± 244.5 mg/dL) were significantly lower than those in the CE group (860.8 ± 456.5 mg/dL) (p < 0.0087). The mean hemoglobin concentration was significantly lower in the DE group (11.8 g/dL) than in the CE group (13.4 g/dL) (p < 0.05). The most frequent (48%) possible decompensation trigger factor was infection. Most of the events were registered in eutrophic patients (87.9%), despite which 65.2% and 50% of patients who experienced decompensated and compensated events, respectively, presented with hypogammaglobulinemia G. These findings provide evidence of the immunodeficiency of PD patients, independent of their nutritional status. We suggest that PD patients be managed as immunocompromised independently of their nutritional status or metabolic state (compensated or decompensated).

Molecular and clinical characterization of a founder mutation causing G6PC3 deficiency.

Background: G6PC3 deficiency is a rare genetic disorder that causes syndromic congenital neutropenia. It is driven by the intracellular accumulation of a metabolite named 1,5-anhydroglucitol-6-phosphate (1,5-AG6P) that inhibits glycolysis. Patients display heterogeneous extra-hematological manifestations, contributing to delayed diagnosis. Objective: The G6PC3 c.210delC variant has been identified in patients of Mexican origin. We set out to study the origin and functional consequence of this mutation. Furthermore, we sought to characterize the clinical phenotypes caused by it. Methods: Using whole-genome sequencing data, we conducted haplotype analysis to estimate the age of this allele and traced its ancestral origin. We examined how this mutation affected G6PC3 protein expression and performed extracellular flux assays on patient-derived cells to characterize how this mutation impacts glycolysis. Finally, we compared the clinical presentations of patients with the c.210delC mutation relative to other G6PC3 deficient patients published to date. Results: Based on the length of haplotypes shared amongst ten carriers of the G6PC3 c.210delC mutation, we estimated that this variant originated in a common ancestor of indigenous American origin. The mutation causes a frameshift that introduces a premature stop codon, leading to a complete loss of G6PC3 protein expression. When treated with 1,5-anhydroglucitol (1,5-AG), the precursor to 1,5-AG6P, patient-derived cells exhibited markedly reduced engagement of glycolysis. Clinically, c.210delC carriers display all the clinical features of syndromic severe congenital neutropenia type 4 observed in prior reports of G6PC3 deficiency. Conclusion: The G6PC3 c.210delC is a loss-of-function mutation that arose from a founder effect in the indigenous Mexican population. These findings may facilitate the diagnosis of additional patients in this geographical area. Moreover, the in vitro 1,5-AG-dependent functional assay used in our study could be employed to assess the pathogenicity of additional G6PC3 variants.

High-precision frequency-controlled optical phase shifter with acousto-optic devices.

A fundamental parameter to determine how electromagnetic waves interfere is their relative phase, and achieving a fine control over it enables a wide range of interferometric applications. Existing phase control methods rely on modifying the optical path length either by changing the path followed by the light or by altering the thickness or index of refraction of an optical element in the setup. In this Letter, we present a novel, to the best of our knowledge, method, based on acousto-optic modulators (AOMs), which allows adjusting the phase by shifting the frequency of the light in a segment of its path. Since the amount of phase shift depends on the length of the segment, an optical fiber is used to realize a 2π shift. Two experimental implementations are described which deal with different sources of phase fluctuations. The first addresses fluctuations resulting from the optical fiber, while the second tackles unwanted variations originating from the AOMs.

Electrostatic assembly of a multicomponent peptide/amphiphile nanotube.

The ability to integrate the elements of a multicomponent nanostructure with nanoscale precision by co-assembly provides a versatile strategy to create novel materials with tunable properties. The search for function in these materials will require new strategies to be developed that control the assembly process, especially for structurally dissimilar components, which often have a propensity to self-sort into non-integrated nanostructures. In this work, two components, a peptide (1) and an amphiphile (2), were integratively co-assembled into a multicomponent nanotube. The interaction between the two components at the supramolecular level was driven by the electrostatic complementarity of the components, which was controlled by the pH-dependent charge of 1. Characterization of the co-assembled nanotube, 1-2NT, was achieved using a combination of TEM, AFM, CLSM and SIM techniques, which showed that both components were colocalized within the nanotube. These studies, in conjunction with CD, IR and fluorescence studies, suggested that 1 and 2 were arranged in partially reorganized, self-sorted domains, which were integrated as laminated nanoribbons that coiled together into the final co-assembled nanotube.

Why are you hitting yourself? Whole-exome sequencing diagnosis of monogenic autoimmunity.

Inborn errors of immunity may present with autoimmunity and autoinflammation as hallmark clinical manifestations. We aimed to identify the potential monogenic causes of autoimmune disorders in 26 patients from a pediatric reference hospital in Mexico through whole-exome sequencing. We specifically selected patients with a family history of autoimmune diseases, early-onset symptoms, and difficult-to-control autoimmune disorders or autoimmunity associated with infection predisposition. We identified the genetic variants that were compatible with the patients' phenotype in 54% of the patients. Autoimmune diseases are often caused by a combination of genetic factors, but cases that appear at a young age are resistant to treatment or occur in clusters, as well as the presence of autoimmune symptoms alongside infectious diseases should raise suspicion for an underlying inborn error of immunity.

Influencia de la percepción de la calidad de atención sobre la salud en estudiantes universitarios / Influence of the quality perception of care on health in university students

Resumen Objetivo: La percepción de la calidad de atención al paciente es una línea de atención que ha quedado relegada en la población universitaria, ya que estos cuentan con el derecho a la atención médica por parte de la universidad, sin embargo, existen factores tanto del sector salud y universitarios que disminuyan las prácticas saludables en los estudiantes universitarios. El objetivo del presente estudio fue evaluar como perciben la calidad de atención en salud sobre la percepción y las prácticas de salud en los estudiantes de la Universidad de Quintana Roo a través de un modelo de ecuaciones estructurales. Materiales y Métodos: Se encuestaron a 401 estudiantes de la Universidad Autónoma del Estado de Quintana Roo, mayores de 20 años, 70% mujeres y 30% hombres. Se aplicaron las escalas de percepción de la calidad de atención en el servicio médico, calidad del servicio de promoción de salud por parte de la universidad y la percepción de salud en el estudiante; mediante un modelo estructural se analizó la relación entre la calidad de los servicios con el cuidado de la salud. Resultados: La percepción de una adecuada calidad de atención en las instituciones de salud y en la universidad influye significativamente en la percepción positiva de salud de los estudiantes (p<0.05). Por otra parte, se encontró que un 70% de los estudiantes no cuentan con acciones preventivas de salud. Conclusión: La percepción de salud y las prácticas preventivas pueden verse influenciadas por la calidad en los servicios que se les ofrecen en la institución de salud y en la universidad.

Abstract Objective: The quality perception of patient care is a line of care that has been relegated in the university students, since they have the right to medical care from the university, however, there are factors both in the health sector and in the university that decrease healthy practices in university students. The objective of this study was to evaluate how to perceive the quality of health care on the perception and practices of health in the students of the University of Quintana Roo through a model of structural equations. Materials and methods: A total of 401 students from the Autonomous University of the State of Quintana Roo over the age of 20, 70% women and 30% men, were surveyed. The scales of perception of the quality of care in the medical service, quality of the health promotion service by the university and the perception of health in the student were applied; Using a structural model, the relationship between the quality of services and health care was analyzed. Results: The perception of an adequate quality of care in health institutions and university influences possitively the perception of health of students (p<0.05). On the other hand, it was found that 70% of the students do not have preventive health actions. Conclusion: The perception of health and preventive practices can be influenced by the quality of the services offered at the health institution and university.

Photothermal Modulation of Dynamic Covalent Poly(ethylene glycol)/PEDOT Composite Hydrogels for On-Demand Drug Delivery.

Hydrogels are cross-linked three-dimensional polymer networks that have tissue-like properties. Dynamic covalent bonds (DCB) can be utilized as hydrogel cross-links to impart injectability, self-healing ability, and stimuli responsiveness to these materials. In our research, we utilized dynamic thiol-Michael bonds as cross-links in poly(ethylene glycol) (PEG)-based hydrogels. Because the equilibrium of the reversible, exothermic thiol-Michael reaction can be modulated by temperature, we investigated the possibility of using thermal and photothermal stimuli to modulate the gel-to-sol transition of these materials with the aim of developing an on-demand pulsatile cargo release system. For this purpose, we incorporated poly(3,4-ethylenedioxythiophene) (PEDOT) nanoparticles within the hydrogel to facilitate photothermal modulation using near-infrared light. PEDOT nanoparticles of 50 nm in diameter and with strong near-infrared absorption were prepared by oxidative emulsion polymerization. We then used Michael addition of thiol-ene pairs from 4-arm PEG-thiol (PEG-SH) and 4-arm PEG-benzylcyanoacetamide (PEG-BCA) to form dynamically cross-linked hydrogels. PEDOT nanoparticles were entrapped in situ to form Gel/PEDOT composites. Rheology and inverted tube test studies showed that the gel-to-sol transition occurred at 45-50 °C for 5 wt % gels and that this transition could be tailored by varying the wt % of the polymer precursors. The hydrogels were found to be capable of self-healing and being injected with a clinically relevant injection force. Bovine serum albumin-fluorescein isothiocyanate (BSA-FITC), a fluorescently labeled protein, was then loaded into the Gel/PEDOT as a therapeutic mimic. Increased release of BSA-FITC upon direct thermal stimulation and photothermal stimulation with an 808 nm laser was observed. Pulsatile release of BSA-FITC over seven cycles was demonstrated. MTS and live-dead assays demonstrated that Gel/PEDOT was cytocompatible in MDA-MB-231 breast cancer and 3T3 fibroblast cell lines. Further studies demonstrated that the encapsulation and laser-triggered release of the chemotherapeutic agent doxorubicin (DOX) could also be achieved. Altogether, this work advances our understanding of the temperature-dependent behavior of a dynamic covalent hydrogel, Gel/PEDOT, and leverages that understanding for application as a photothermally responsive biomaterial for controlled release.

La adaptación transcultural, confiabilidad y validez del instrumento actitudes y conocimientos de seguridad del paciente / The cross-cultural adaptation, reliability and validity of the instrument attitudes and knowledge of patient safety

Resumen Objetivo: La seguridad del paciente busca reducir los riesgos y ocurrencia de daño evitable, y que los errores sean menos probables en la población que recibe atención sanitaria. La formación de recursos humanos en salud es considerada como un elemento fundamental para generar cambios en la práctica sanitaria y contribuir a disminuir o limitar los errores, así como tener procesos más seguros. El objetivo de esta investigación es adaptar y validar el "Cuestionario para medir actitudes y conocimientos de seguridad del paciente" para su aplicación con estudiantes de enfermería y medicina de una Universidad Pública de Medicina y Enfermería del Caribe Mexicano. Materiales y Métodos: Estudio transversal, observacional, con aplicación de encuesta anónima y voluntaria. La muestra incluyó a 220 estudiantes (120 mujeres y 100 hombres) con una edad promedio de 24 años (DE=2) matriculados en una Universidad Pública de medicina y enfermería del Caribe Mexicano. 46% se encontraban realizando Internado de pregrado y 54% en prácticas de Servicio Social. El instrumento presentó 1 ficha de identificación y 21 reactivos tipo Likert. Resultados: A través del Análisis Factorial Exploratorio (AFE) se fijó a cinco factores con el método de Máxima Verosimilitud y rotación Varimax sobre los 21 reactivos del cuestionario de seguridad del paciente para estudiantes mexicanos, resultando una escala de cinco factores que explican el 63.59% de la varianza total y un índice de consistencia interna de la escala total aceptable (α=.87). Conclusiones: El cuestionario para medir actitudes y conocimientos sobre seguridad del paciente adaptado en los estudiantes de medicina y enfermería es válido, confiable y útil para medir las acciones de seguridad del paciente para la prevención del error en la atención sanitaria.

Abstract Objective: Patient safety seeks to reduce the risk and occurrence of avoidable harm, and to make errors less common in the population that receive health care. The training of human resources in health is considered a fundamental element to generate changes in health practices and contribute to reducing errors, furthermore safer processes. The objective of the present study is adapt and validate the "Questionnaire to measure attitudes and knowledge of patient safety" for its application with nursing and medical students of Public University of Medicine and Nursing in the Mexican Caribbean. Materials and methods: A cross-sectional, observational study, with the application of an anonymous and voluntary survey. The sample included 220 students (120 women and 100 men) with an average age of 24 years (SD=2) a Public University of Medicine and Nursing in the Mexican Caribbean. The 46% were undergraduate internship and 54% in Social Service practices. The instrument presented one identification card and 21 Likert-type items. Results: Through the Exploratory Factor Analysis (EFA), five factors were set with the Maximum Likelihood method and Varimax rotation on the 21 items of the patient safety questionnaire for Mexican students, resulting five factors that explain 63.59% of the total variance and an internal consistency index of the acceptable total scale (α=.87). Conclusions: The questionnaire to measure attitudes and knowledge about patient safety translated and adapted to medical and nursing students is valid, reliable and useful to measure patient safety actions for the prevention of errors in health care.

Bond strength comparison among 10-MDP-containing and non-10-MDP-Containing adhesives in different degrees of dental fluorosis / Comparación de fuerza de unión entre adhesivos que contienen y no contienen 10-MDP en diferentes grados de fluorosis dental

Dental fluorosis can cause changes in the enamel surface, conditioning its functionality and esthetics. The application of dental adhesives is a treatment option; however, their use on fluorotic teeth can result in limitations. The aim of this study was to compare the shear bond strength of two different adhesives, one with 10-MDP and one without 10-MDP, in different degrees of dental fluorosis.This is an in vitro study on dental enamel samples, a total of 180 samples with the inclusion criteria were treated, randomly divided into two groups of 90, according to the type of dental adhesive, where each group was again divided into three groups of 30 samples, representing different degrees of dental fluorosis according to the Thylstrup-Fejerskov index (Group I: TF1 and TF2; Group II: TF3; Group III: TF4). Normality tests, two-factor ANOVA, and post-hoc tests were used to determine differences between the groups, with a significance level of 95%. As results, a statistically significant difference was shown between the use of dental adhesive with 10-MDP and the three groups of dental fluorosis (p=0.011), in addition, a Tukey post-hoc test on the groups treated with 10-MDP adhesive revealed a statistically significant difference between group I versus group II, and group I versus group III, (p=<0.05). It is concluded that the use of adhesive systems with 10-MDP presents a better shear bond strength on enamel with dental fluorosis grades I and II in the Thylstrup-Fejerskov index.

La fluorosis dental puede ocasionar cambios en la superficie del esmalte, condicionando su funcionalidad y estética, la aplicación de adhesivos dentales es una opción de tratamiento, sin embargo, su uso en dientes fluoroticos puede resultar en limitaciones. El objetivo de este estudio consistió en comparar la fuerza de adhesión a la cizalladura de dos diferentes adhesivos, uno con 10-MDP y otro sin 10-MDP, en diferentes grados de fluorosis dental. Se trata de un estudio in vitro en muestras de esmalte dental, un total de 180 muestras con los criterios de inclusión fueron tratadas, aleatoriamente divididas en dos grupos de 90, de acuerdo al tipo de adhesivo dental, donde cada grupo fue dividido nuevamente en tres grupos de 30 muestras, representando diferentes grados de fluorosis dental según el índice de Thylstrup- Fejerskov (Grupo I: TF1 y TF2; Grupo II: TF3; Grupo III: TF4). Para determinar diferencias entre los grupos se utilizaron pruebas de normalidad, ANOVA de dos factores, y pruebas post-hoc, con un nivel de significancia de 95%. Como resultados, se mostró una diferencia estadísticamente significativa entre el uso de adhesivo dental con 10- MDP y los tres grupos de fluorosis dental (p=0.011), además, una prueba post hoc de Tukey sobre los grupos tratados con adhesivo 10-MDP revelaron una diferencia estadísticamente significativa entre el grupo I frente al grupo II, y el grupo I frente al grupo III, (p=<0.05) Se concluye que el uso de sistemas adhesivos con 10-MDP presentan una mejor resistencia de adhesión al cizallamiento en esmalte con grados de fluorosis dental I y II en el índice de Thylstrup-Fejerskov

Análisis médico legal de la fractura de órbita por "blow out" o estallido: reporte de caso / Medical-legal analysis of blow out fracture of the orbit: case report

La fractura orbitaria por estallido o fractura en "blow out" es una de las fracturas más comunes a nivel facial por lo que su importancia reside en saber identificarlas por el enmascaramiento clínico que podría o no, estar presente. Es de vital importancia complementar la valoración clínica con estudios de imagenología que confirmen las sospechas clínicas. De no hacerlo si el paciente no consulta a un servicio médico quirúrgico la pérdida de la capacidad funcional o la debilitación persistente en la salud ocasionada por la fractura no podrá ser validada en un Dictamen Médico Legal de Secuelas.

The orbital blow out fracture is one of the most common fractures at facial level, so its importance lies in knowing how to identify them due to the clinical masking that may or may not be present. It is of vital importance to complement the clinical evaluation with imaging studies to confirm the clinical suspicions. Otherwise, if the patient does not consult a surgical medical service, the loss of functional capacity or the persistent debilitation in health caused by the fracture cannot be validated in a Forensic Medical Report of Sequelae.

Is Your Kid Actin Out? A Series of Six Patients With Inherited Actin-Related Protein 2/3 Complex Subunit 1B Deficiency and Review of the Literature.

BACKGROUND: Hereditary actin-related protein 2/3 complex subunit 1B deficiency is characterized clinically by ear, skin, and lung infections, bleeding, eczema, food allergy, asthma, skin vasculitis, colitis, arthritis, short stature, and lymphadenopathy. OBJECTIVE: We aimed to describe the clinical, laboratory, and genetic features of six patients from four Mexican families. METHODS: We performed exome sequencing in patients of four families with suspected actinopathy, collected their data from medical records, and reviewed the literature for reports of other patients with actin-related protein 2/3 complex subunit 1B deficiency. RESULTS: Six patients from four families were included. All had recurrent infections, mainly bacterial pneumonia, and cellulitis. A total of 67% had eczema whereas 50% had food allergies, failure to thrive, hepatomegaly, and bleeding. Eosinophilia was found in all; 84% had thrombocytopenia, 67% had abnormal-size platelets and anemia. Serum levels of IgG, IgA, and IgE were highly increased in most; IgM was normal or low. T cells were decreased in 67% of patients, whereas B and NK cells were increased in half of patients. Two of the four probands had compound heterozygous variants. One patient was successfully transplanted. We identified 28 other patients whose most prevalent features were eczema, recurrent infections, failure to thrive, bleeding, diarrhea, allergies, vasculitis, eosinophilia, platelet abnormalities, high IgE/IgA, low T cells, and high B cells. CONCLUSION: Actin-related protein 2/3 complex subunit 1B deficiency has a variable and heterogeneous clinical spectrum, expanded by these cases to include keloid scars and Epstein-Barr virus chronic hepatitis. A novel deletion in exon 8 was shared by three unrelated families and might be the result of a founder effect.

Efficacy and Safety of Interferon-Gamma in Chronic Granulomatous Disease: a Systematic Review and Meta-analysis.

BACKGROUND: Chronic granulomatous disease (CGD) is a primary immunodeficiency with increased susceptibility to several bacteria, fungi, and mycobacteria, caused by defective or null superoxide production by the NADPH oxidase enzymatic complex. Accepted treatment consists mainly of antimicrobial prophylaxis. The role of human recombinant subcutaneous interferon-gamma (IFNγ) is less clear since the available evidence on its efficacy derives mainly from a single clinical trial that has been challenged. OBJECTIVE: We aimed to assess the efficacy and safety of IFNγ as an added treatment for CGD when compared to antimicrobial prophylaxis alone. METHODS: A literature search was conducted using MeSH terms "Chronic granulomatous disease" AND ("interferon gamma" OR "interferon-gamma"), as well as antibiotics, placebo, no therapy, clinical trial, and trial, on MEDLINE, EMBASE, LILACS, WHOs, CENTRAL, KOREAMED, The Cochrane Library, clinicaltrials.gov, and abstracts from meetings, from 1976 to July 2022. We included clinical trials (CT) and prospective follow-up studies and registered the number of serious infections (requiring hospitalization and IV antibiotics) and deaths, adverse events, and autoimmune complications, in patients treated for CGD with antimicrobial prophylaxis plus IFN-γ, versus antimicrobial prophylaxis alone. We assessed the quality of the studies using risk of bias and STROBE. We performed a meta-analysis by calculating both Peto's odds ratio (OR) and risk reduction (RR) through the Mantel-Haenszel method with a fixed-effect model, using Review Manager 5.4, and we reported the number needed to treat (NNT). RESULTS: We identified 54 matches from databases and 4 from other sources. We excluded 12 duplicates, 7 titles, and 9 abstracts for relevance, after which we had 30 eligible studies. Twenty-four were then excluded after reading the full text. Six papers were included: one randomized CT and 5 follow-up studies. In total, 324 patients with Chronic granulomatous disease were followed for 319 months under treatment with antibiotic prophylaxis plus interferon-gamma or placebo (or antibiotic prophylaxis alone), reported between the years 1991 and 2016. Three of the studies included a control group, allowing for the aggregate analysis of efficacy (prevention of serious infections). The aggregate OR was 0.49, with a 95% confidence interval of 0.19 to 1.23. The risk ratio for serious infection was 0.56 (95%CI 0.35-0.90) under IFN-γ. The meta-analysis thus favors interferon-gamma for a risk reduction of serious infection. DISCUSSION: The results from this meta-analysis support the use of IFN-γ in the treatment of patients with CGD. However, we found insufficient clinical evidence and believe more clinical trials are needed to better assess the efficacy and long-term safety of IFN-γ.

Mendelian Susceptibility to Mycobacterial Disease: Retrospective Clinical and Genetic Study in Mexico.

Mendelian susceptibility to mycobacterial disease (MSMD) is a rare genetic disorder characterized by impaired immunity against intracellular pathogens, such as mycobacteria, attenuated Mycobacterium bovis-Bacillus Calmette-Guérin (BCG) vaccine strains, and environmental mycobacteria in otherwise healthy individuals. Retrospective study reviewed the clinical, immunological, and genetic characteristics of patients with MSMD in Mexico. Overall, 22 patients diagnosed with MSMD from 2006 to 2021 were enrolled: 14 males (64%) and eight females. After BCG vaccination, 12 patients (70%) developed BCG infection. Furthermore, 6 (22%) patients developed bacterial infections mainly caused by Salmonella, as what is described next in the text is fungal infections, particularly Histoplasma. Seven patients died of disseminated BCG disease. Thirteen different pathogenic variants were identified in IL12RB1 (n = 13), IFNGR1 (n = 3), and IFNGR2 (n = 1) genes. Interleukin-12Rß1 deficiency is the leading cause of MSMD in our cohort. Morbidity and mortality were primarily due to BCG infection.

Activating de novo monoallelic variants causing inborn errors of immunity in two unrelated children born of HIV-seroconcordant couples.

INTRODUCTION: Around 20% of all inborn errors of immunity (IEI) are autosomal dominant or monoallelic, either by haploinsufficiency, negative dominance, or gain of function (GOF). GOF phenotypes usually include autoinflammation, autoimmunity, lymphoproliferation, allergies, and some infections. CASE SERIES: We describe the cases of two unrelated patients born of HIV-seroconcordant parents. Both patients are HIV-negative but carry de novo GOF missense variants that resulted in inflammatory lymphoproliferative IEI diseases: signal transducer and activator of transcription 3 (STAT3)-GOF and phosphatidylinositol 3-kinase, catalytic delta (PIK3CD)-GOF. Both variants were found through whole-exome sequencing and confirmed by Sanger.An 11-year-old male with recurrent sinopulmonary infections, dysmorphism, growth delay, bronchiectasis, and mild mental retardation, as well as lymphopenia, thrombocytopenia, and high immunoglobulin M. Both his parents were known to be HIV-positive under anti-retroviral treatment. HIV infection was repeatedly ruled out in the patient, whom through whole-exome sequencing was found to have a heterozygous missense variant in exon 24 of PIK3CD, a hotspot transition, and the most reported variant in PIK3CD-GOF patients.A 6-year-old male with autoimmune hemolytic anemia, lymphoproliferation, short stature, and intractable diarrhea. Both his parents were found to be HIV-positive. HIV was repeatedly ruled out in the patient by ELISA and viral load. He was found to have a heterozygous missense/splice variant in exon 22 of STAT3, a hotspot transition, and the most reported variant in STAT3-GOF patients. DISCUSSION: The AID/APOBEC3 A-H family of proteins are cytidine deaminases that induce G>A hypermutation in both the invading viral DNA and the host genome, which results in stop codons inside the endogenized retroviral sequence. Both variants found in our patients are G to A transitions. Retroviral infection might thus have resulted in host genome instability, and our patients' rare congenital diseases are the unfortunate consequence of somatic hypermutation in one of their parents' gametes.

Not enough by half: NFAT5 haploinsufficiency in two patients with Epstein-Barr virus susceptibility.

Introduction: The transcription factor Nuclear factor of activated T cells 5 (NFAT5), pivotal in immune regulation and function, can be induced by osmotic stress and tonicity-independent signals. Objective: We aimed to investigate and characterize two unrelated patients with Epstein-Barr virus susceptibility and no known genetic etiology. Methods: After informed consent, we reviewed the electronic charts, extracted genomic DNA, performed whole-exome sequencing, filtered, and prioritized their variants, and confirmed through Sanger sequencing, family segregation analysis, and some functional assays, including lymphoproliferation, cytotoxicity, and characterization of natural killer cells. Results: We describe two cases of pediatric Mexican patients with rare heterozygous missense variants in NFAT5 and EBV susceptibility, a school-age girl with chronic-active infection of the liver and bowel, and a teenage boy who died of hemophagocytic lymphohistiocytosis. Discussion: NFAT5 is an important regulator of the immune response. NFAT5 haploinsufficiency has been described as an immunodeficiency syndrome affecting both innate and adaptive immunity. EBV susceptibility might be another manifestation in the spectrum of this disease.

Proteolytic activities and profiles as useful traits to select barley cultivars for beer production.

Barley malting depends on hydrolytic enzymes that degrade storage macromolecules. Identifying barley cultivars with proteolytic activity that guarantees appropriate foaming, flavor, and aroma in the beer is of great importance. In this work, the proteolytic activity and profiles of brewing malt from Mexican barley cultivars were analyzed. Data showed that Cys- (at 50°C) and Ser-proteases (at 70°C) are the major contributors to proteolytic activity during mashing. Essential amino acids, necessary for fermentation and production of good flavor and aroma in beer, were detected at the end of mashing. According to our results, Mexican cultivar HV2005-19 exhibits similar proteolytic activities as those from cultivar Metcalfe, which is one of the most utilized for the brewing industry. Moreover, we propose Cys- and Ser-proteases as biochemical markers during mashing at 50 and 70°C, respectively, to select barley cultivars for beer production. PRACTICAL APPLICATIONS: Proteolytic activity, which depends on activation and de novo synthesis of proteases in the aleurone layer of barley seeds, is crucial in beer production. Identifying new barley varieties that have optimal proteolytic activities is of great interest for genetic improvement programs. In this study, we propose the variety HV2005-19 as a genotype with Cys- and Ser-proteases activity similar to that from Metcalfe, which is a top variety in the brewing industry.

Análisis médico legal de la toxicomanía por MDMA: reporte de caso / Medical-legal relationship of MDMA drug addiction: case report

Resumen El análisis por toxicomanía representa un proceso común solicitado por la Autoridad Judicial para determinar si un usuario presenta hallazgos compatibles con el uso de una droga a nivel clínico, componentes histológicos, patológicos y toxicológicos que puedan generar su uso. Es necesario destacar las limitaciones del ambiente clínico donde se pueden generar múltiples hallazgos, y de la toxicología forense donde a pesar de la especificidad a la que se asocia; también se encuentra limitada por la capacidad de sus equipos tecnológicos. La resonancia magnética nuclear cuantitativa de hidrógeno representa grandes ventajas al demostrar la presencia de una droga ilegal, así como la posibilidad de disminuir costos y tiempo laboral. El uso del MDMA como tratamiento con una reciente aprobación para un estudio de fase III por la FDA, también requiere que se valore el motivo de su uso, por lo que para realizar un análisis médico legal se contemplaron diversos elementos de juicio a fin de satisfacer la evaluación sobre la toxicomanía por MDMA en un usuario que presentó un tejido granular blanco tipo polvo en la sección distal del tabique nasal y negó el consumo de metanfetaminas.

Abstract The analysis for drug addiction represents a common process requested by the Judicial Authority to determine if a user presents findings compatible with the use of a drug at a clinical level, histological, pathological and toxicological components that may generate its use. It is necessary to highlight the limitations of the clinical environment where multiple findings can be generated, and of forensic toxicology where despite the specificity to which it is associated; it is also limited by the capacity of its technological equipment. Quantitative hydrogen nuclear magnetic resonance represents great advantages when demonstrating the presence of an illegal drug, as well as the possibility of reducing costs and labor time. The use of MDMA as a treatment with a recent approval for a phase III study by the FDA, also requires that the reason for its use be assessed, therefore, in order to carry out a legal medical analysis, various elements of judgment were considered in order to satisfy evaluation of MDMA drug addiction in a user who presented with white powder-like granular tissue in the distal section of the nasal septum and denied the use of methamphetamine.

Growth performance, carcass traits, muscle fiber characteristics and skeletal muscle mRNA abundance in hair lambs supplemented with ferulic acid.

Ferulic acid (FA) is a phytochemical with various bioactive properties. It has recently been proposed that due to its phytogenic action it can be used as an alternative growth promoter additive to synthetic compounds. The objective of the present study was to evaluate the growth performance, carcass traits, fiber characterization and skeletal muscle gene expression on hair-lambs supplemented with two doses of FA. Thirty-two male lambs (n = 8 per treatment) were individually housed during a 32 d feeding trial to evaluate the effect of FA (300 and 600 mg d-1) or zilpaterol hydrochloride (ZH; 6 mg d-1) on growth performance, and then slaughtered to evaluate the effects on carcass traits, and muscle fibers morphometry from Longissimus thoracis (LT) and mRNA abundance of ß2-adrenergic receptor (ß2-AR), MHC-I, MHC-IIX and IGF-I genes. FA increased final weight and average daily gain with respect to non-supplemented animals (p < 0.05). The ZH supplementation increased LT muscle area, with respect to FA doses and control (p < 0.05). Cross-sectional area (CSA) of oxidative fibers was larger with FA doses and ZH (p < 0.05). Feeding ZH increased mRNA abundance for ß2-AR compared to FA and control (p < 0.05), and expression of MHC-I was affected by FA doses and ZH (p < 0.05). Overall, FA supplementation of male hair lambs enhanced productive variables due to skeletal muscle hypertrophy caused by MHC-I up-regulation. Results suggest that FA has the potential like a growth promoter in lambs.

Perfil epidemiológico y presencia de polimorfismos IFR6 (rs2235371), TGFA (rs3771494) en individuos con labio y paladar hendido no sindrómico / Epidemiological profile and presence of IFR6 (rs2235371), TGFA (rs3771494) polymorphisms in individuals with non-syndromic cleft lip and palate

Objetivo. Reportar el perfil epidemiológico y presencia de polimorfismos de IFR6 (rs2235371) y TGFA (rs3771494) en individuos con labio y paladar hendido (LPH) no sindrómico. Métodos. Serie de casos, centrado en individuos con hendiduras orofaciales (HO), remitidos a la Facultad de Odontología de Durango, México, para su revisión y valoración dentro del periodo comprendido de enero-2018 a diciembre-2019. Se obtuvo información de interés para el estudio sobre las características del embarazo y anteceden- tes familiares, de las madres de los individuos. Para el análisis y descripción de los datos se utilizó el paquete estadístico R Studio. Resultados. El total de casos estudiados fue de 24. Se presentó una mayor frecuencia de hombres (67%), la mayoría de los individuos tuvieron el diagnóstico de LPH al nacer (75%), extensión de afección completa (75%), el lado izquierdo afectado (63%), y cirugías correctivas (62%). Solo el 4% estuvo ex- puesto al tabaquismo materno (activo y pasivo), el 96% tuvo adecuada ingesta de ácido fólico y hierro; el genotipo de riesgo para TGFA (rs3771494) se presentó en el 15% de labio hendido y en el 8% del LPH, y para IFR6 (rs2235371) solo en el 10% del LPH. Conclusiones. La presencia de factores ambientales, genéticos, y el estilo de vida ma- terno mostrado en otras poblaciones, podrían no ser los mismos que intervengan en la aparición y desarrollo de HO no sindromicas de nuestra localidad, además, la presencia de los genotipos homocigotos polimórficos de los genes de interés podría no condicionar el desarrollo de HO.

Objective. To report the epidemiological profile and the presence of polymorphisms of the IFR6 (rs2235371) and TGFA (rs3771494) genes, in individuals with non-syndromic cleft lip and palate. Methods. Case series study, focused on individuals with orofacial clefts, referred to the School of Dentistry of Durango, Mexico, for review and assessment within the period from January 2018 to December 2019. Information of interest for the study was obtained on the characteristics of pregnancy and family history of the mothers of the individuals. For the analysis and description of the data, the statistical software R Studio was used. Results. There was a higher frequency of men (67%), most of the individuals had the diagnosis of cleft lip and palate at birth (75%), the extension of the complete affection (75%), the left side affected (63%), and corrective surgeries (62%). Only 4% were exposed to maternal smoking (active and passive), 96% had adequate folic acid and iron intake; the risk genotype for TGFA (rs3771494 [G/G]) was present in 15% of cleft lip and 8% of cleft lip and palate, and for IFR6 (rs2235371 [T/T]) only in 10% of cleft lip and palate. Conclusions. The presence of environmental and genetic factors, as well as the maternal lifestyle shown in other populations, may not be the same as those involved in the appearance and development of non-syndromic orofacial clefts in our locality, in addition, the presence of homozygous polymorphic genotypes of the genes of interest could not condition the development of orofacial clefts.