Discovery and Preclinical Pharmacology of NX-2127, an Orally Bioavailable Degrader of Bruton's Tyrosine Kinase with Immunomodulatory Activity for the Treatment of Patients with B Cell Malignancies.

Bruton's tyrosine kinase (BTK), a member of the TEC family of kinases, is an essential effector of B-cell receptor (BCR) signaling. Chronic activation of BTK-mediated BCR signaling is a hallmark of many hematological malignancies, which makes it an attractive therapeutic target. Pharmacological inhibition of BTK enzymatic function is now a well-proven strategy for the treatment of patients with these malignancies. We report the discovery and characterization of NX-2127, a BTK degrader with concomitant immunomodulatory activity. By design, NX-2127 mediates the degradation of transcription factors IKZF1 and IKZF3 through molecular glue interactions with the cereblon E3 ubiquitin ligase complex. NX-2127 degrades common BTK resistance mutants, including BTKC481S. NX-2127 is orally bioavailable, exhibits in vivo degradation across species, and demonstrates efficacy in preclinical oncology models. NX-2127 has advanced into first-in-human clinical trials and achieves deep and sustained degradation of BTK following daily oral dosing at 100 mg.

Fontan surgery failure: risk factors and experience in a Colombian reference centre.

BACKGROUND: The Fontan procedure is considered one of the most remarkable achievements in paediatric cardiology and cardiac surgery. Its final anatomical objective is a venous return through the superior and inferior vena cava. The complications inherent to this procedure and subsequent failure are its limitations. OBJECTIVE: To describe the clinical and haemodynamic characteristics of patients with Fontan failure and define the risk factors associated with it, with its short- and long-term outcomes during a 21-year observation period. METHODS: This is a retrospective follow-up study in which 15 patients diagnosed with Fontan failure in the single-ventricle programme of a high-complexity hospital in Medellín, Colombia, between 2001 and 2022 were included. RESULTS: One hundred and eight patients were identified in whom the Fontan procedure was performed, and 17 met the failure criteria. 82.4% were men, with a median age of 4.3 years. Ebstein's anomaly was the most common diagnosis, 29.4%. All patients underwent Fontan with an extracardiac tube following the procedure. According to the type of failure, 58.8% of patients presented protein-losing enteropathy and 17.6% plastic bronchitis. During follow-up, 5.9% of patients died. CONCLUSION: Fontan surgery in our centre is an option for patients with univentricular physiology. The correct selection of the patient is essential to mitigate failure risks.

Quantitative Lipid Profiling Reveals Major Differences between Liver Organoids with Normal Pi*M and Deficient Pi*Z Variants of Alpha-1-antitrypsin.

Different mutations in the SERPINA1 gene result in alpha-1 antitrypsin (AAT) deficiency and in an increased risk for the development of liver diseases. More than 90% of severe deficiency patients are homozygous for Z (Glu342Lys) mutation. This mutation causes Z-AAT polymerization and intrahepatic accumulation which can result in hepatic alterations leading to steatosis, fibrosis, cirrhosis, and/or hepatocarcinoma. We aimed to investigate lipid status in hepatocytes carrying Z and normal M alleles of the SERPINA1 gene. Hepatic organoids were developed to investigate lipid alterations. Lipid accumulation in HepG2 cells overexpressing Z-AAT, as well as in patient-derived hepatic organoids from Pi*MZ and Pi*ZZ individuals, was evaluated by Oil-Red staining in comparison to HepG2 cells expressing M-AAT and liver organoids from Pi*MM controls. Furthermore, mass spectrometry-based lipidomics analysis and transcriptomic profiling were assessed in Pi*MZ and Pi*ZZ organoids. HepG2 cells expressing Z-AAT and liver organoids from Pi*MZ and Pi*ZZ patients showed intracellular accumulation of AAT and high numbers of lipid droplets. These latter paralleled with augmented intrahepatic lipids, and in particular altered proportion of triglycerides, cholesterol esters, and cardiolipins. According to transcriptomic analysis, Pi*ZZ organoids possess many alterations in genes and cellular processes of lipid metabolism with a specific impact on the endoplasmic reticulum, mitochondria, and peroxisome dysfunction. Our data reveal a relationship between intrahepatic accumulation of Z-AAT and alterations in lipid homeostasis, which implies that liver organoids provide an excellent model to study liver diseases related to the mutation of the SERPINA1 gene.

Presence of human papillomavirus in the buccal mucosa of blood donors.

OBJECTIVE: To determine the presence of human papillomavirus (HPV) in the oral mucosa of blood donors (BD) and risk factors associated with HPV and oral cancer. MATERIALS AND METHODS: Prospective cross-sectional study, population matched to BD from the National Cancer Institute, Mexico for HPV identification in oral cytological samples using the CLART® Human Papillomavirus 2 Kit (35 genotypes) and risk factors. RESULTS: Of 352 BD with signed informed consent, 285 were selected by simple randomization. The prevalence of oral HPV was 17.5% (95% CI 13-21.9%), the genotype was identified in 13 cases, with a total of 16 genotypes (10 high-risk), the most common being 16 and 84. Five cases had multiple infections, three with at least one high-risk type. Associations were found for marital status (OR 3.3) and educational level (OR-1.9). CONCLUSIONS: The percentage of HPV-positive cases in blood donors with no risk practices was similar to that found in Spanish-speaking population studies in which at least one risk practice was described. The presence of other genotypes with high oncogenic risk and multitype infection, described as a marker of persistence of HPV infection, is highlighted.

NaHS restores the vascular alterations in the renin-angiotensin system induced by hyperglycemia in rats.

Hyperglycemia (HG) impairs the renin-angiotensin system (RAS), which may contribute to vascular dysfunction. Besides, hydrogen sulfide (H2S) exerts beneficial cardiovascular effects in metabolic diseases. Therefore, our study aimed to determine the effects of chronic administration of sodium hydrosulfide (NaHS; inorganic H2S donor) and DL-Propargylglycine [DL-PAG; cystathionine-×¥-lyase (CSE) inhibitor] on the RAS-mediated vascular responses impairments observed in thoracic aortas from male diabetic Wistar rats. For that purpose, neonatal rats were divided into two groups that received: 1) citrate buffer (n = 12) or 2) streptozotocin (STZ, 70 mg/kg; n = 48) on the third postnatal day. After 12 weeks, diabetic animals were divided into 4 subgroups (n = 12 each) that received daily i.p. injections during 4 weeks of: 1) non-treatment; 2) vehicle (PBS, 1 mL/kg); 3) NaHS (5.6 mg/kg); and 4) DL-PAG (10 mg/kg). After treatments (16 weeks), blood glucose, angiotensin-(1-7) [Ang-(1-7)], and angiotensin II (Ang II) levels, vascular responses to Ang-(1-7) and Ang II, and the expression of angiotensin AT1, AT2, and Mas receptors, angiotensin converting enzyme (ACE) and ACE type 2 (ACE2) were determined. HG induced: 1) increased blood glucose levels and expression of angiotensin II AT1 receptor; 2) impaired Ang-(1-7) and Ang II mediated vascular responses; 3) decreased angiotensin levels and expression of angiotensin II AT2 and angiotensin-(1-7) Mas receptors, and ACE2; and 4) no changes in ACE expression. Interestingly, NaHS, but not DL-PAG, reversed HG-induced impairments, except for blood glucose level changes. These results suggest that NaHS restores vascular function in streptozotocin-induced HG through RAS modulation.

Mice inflammatory responses to inhaled aerosolized LPS: effects of various forms of human alpha1-antitrypsin.

Rodent models of lipopolysaccharide (LPS)-induced pulmonary inflammation are used for anti-inflammatory drug testing. We aimed to characterize mice responses to aerosolized LPS alone or with intraperitoneal (i.p.) delivery of alpha1-antitrypsin (AAT). Balb/c mice were exposed to clean air or aerosolized LPS (0.21 mg/mL) for 10 min per day, for 3 d. One hour after each challenge, animals were treated i.p. with saline or with (4 mg/kg body weight) one of the AAT preparations: native (AAT), oxidized (oxAAT), recombinant (recAAT), or peptide of AAT (C-36). Experiments were terminated 6 h after the last dose of AATs. Transcriptome data of mice lungs exposed to clean air versus LPS revealed 656 differentially expressed genes and 155 significant gene ontology terms, including neutrophil migration and toll-like receptor signaling pathways. Concordantly, mice inhaling LPS showed higher bronchoalveolar lavage fluid neutrophil counts and levels of myeloperoxidase, inducible nitric oxide synthase, IL-1ß, TNFα, KC, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Plasma inflammatory markers did not increase. After i.p. application of AATs, about 1% to 2% of proteins reached the lungs but, except for GM-CSF, none of the proteins significantly influenced inflammatory markers. All AATs and C-36 significantly inhibited LPS-induced GM-CSF release. Surprisingly, only oxAAT decreased the expression of several LPS-induced inflammatory genes, such as Cxcl3, Cd14, Il1b, Nfkb1, and Nfkb2, in lung tissues. According to lung transcriptome data, oxAAT mostly affected genes related to transcriptional regulation while native AAT or recAAT affected genes of inflammatory pathways. Hence, we present a feasible mice model of local lung inflammation induced via aerosolized LPS that can be useful for systemic drug testing.

Silver nanoparticles induce a non-immunogenic tumor cell death.

Immunogenic cell death (ICD) is a form of cell death characterized by the release of danger signals required to trigger an adaptive immune response against tumor-associated antigens. Silver nanoparticles (AgNP) display anti-proliferative and cytotoxic effects in tumor cells, but it has not been previously studied whether AgNP act as an ICD inductor. The present study evaluated the in vitro release of calreticulin as a damage-associated molecular pattern (DAMP) associated with the cytotoxicity of AgNP and their in vivo anti-cancer effects. In vitro, mouse CT26 colon carcinoma and MCA205 fibrosarcoma cells were exposed to AgNP and then cell proliferation, adhesion, and release of calreticulin were determined. The results indicated there were time- and concentration-related anti-proliferative effects of AgNP in both the CT26 and MCA205 lines. Concurrently, changes in cell adhesion were detected mainly in the CT26 cells. Regarding DAMP detection, a significant increase in calreticulin was observed only in CT26 cells treated with doxorubicin and AgNP; however, no differences were found in the MCA205 cells. In vivo, the survival and growth of subcutaneous tumors were monitored after vaccination of mice with cell debris from tumor cells treated with AgNP or after intra-tumoral administration of AgNP to established tumors. Consequently, anti-tumoral prophylactic immunization with AgNP-dead cells failed to protect mice from tumor re-challenge; intra-tumor injection of AgNP did not induce a significant effect. In conclusion, there was a noticeable anti-tumoral effect of AgNP in vitro in both CT26 and MCA205 cell lines, accompanied by the release of calreticulin in CT26 cells. In vivo, immunization with cell debris derived from AgNP-treated tumor cells failed to induce a protective immune response in the cancer model mice. Clearly, further research is needed to determine if one could combine AgNP with other ICD inducers to improve the anti-tumor effect of these nanoparticles in vivo.

Patentes otorgadas a las universidades peruanas en el campo de la biomedicina. 2010 a 2020

Introducción: La patente es un título de propiedad industrial otorgado por el Estado al inventor de un nuevo producto o tecnología, susceptible de ser comercializado para obtener ganancias de forma exclusiva a un plazo de tiempo determinado. Objetivo: Determinar el número de patentes otorgadas a las universidades peruanas en el campo biomédico de 2010 a 2020, en comparación con la producción de otros inventores. Material y método: Este estudio descriptivo, observacional, retrospectivo y transversal analizó 73 patentes provenientes de un universo de 759, obtenidas de la base de datos del Instituto Nacional de Defensa de la Competencia y de la Protección de la Propiedad Intelectual en el Perú, de 2010 a 2020. Para comparar el número de patentes otorgadas a las universidades respecto a otros inventores, se aplicó la prueba del Chi Cuadrado de Pearson con la corrección de continuidad de Yates. Resultados: En el Perú, durante 2010 a 2020 se han otorgado 759 patentes, de las cuales 73 pertenecen al campo biomédico (9,61 %), de los cuales las universidades han generado 24,66 %; es decir 2,47 % del total. Además, las universidades presentaron diferencias significativas de producción de patentes (p = 0,019) en comparación a otros autores. Conclusiones: En el campo biomédico, la producción de patentes en las universidades peruanas ha sido muy limitadas desde 2010 a 2020. Además, las universidades presentaron significativamente menor producción de patentes en comparación a otros inventores, observándose que desde 2016, no se les ha otorgado ninguna patente de invención en el campo biomédico.

Introduction: A patent is an industrial property title granted by the State to the inventor of a new product or technology, susceptible of being marketed for profit on an exclusive basis for a determined period of time. Objective: To determine the number of patents granted to Peruvian universities in the biomedical field from 2010 to 2020, in comparison with the production of other inventors. Material and Methods: This descriptive, observational, retrospective and cross-sectional study analyzed 73 patents from a universe of 759 patents obtained from the database of the National Institute for the Defense of Competition and Protection of Intellectual Property in Peru, from 2010 to 2020. To compare the number of patents granted to universities with respect to other inventors, Pearson's chi-square test with Yates' continuity correction was applied. Results: In Peru, during the years 2010 to 2020, 759 patents have been granted, of which 73 belong to the biomedical field (9.61 %), of which universities have generated 24.66 %, i.e. 2.47 % of the total. Furthermore, universities showed significant differences in patent production (p = 0.019) compared to other authors. Conclusions: In the biomedical field, patent production in Peruvian universities has been very limited from 2010 to 2020. In addition, universities presented significantly lower patent production compared to other inventors, noting that since 2016, they have not been granted any invention patents in the biomedical field.

Incidence of acute respiratory symptoms and COVID-19 infection in children in public schools in Bogotá, Colombia, from July to November, 2020 / Incidencia de síntomas respiratorios agudos y COVID-19 en niños de escuelas públicas de Bogotá, Colombia, entre julio y noviembre de 2020

Introduction: More than 90% of children infected with COVID-19 worldwide developed mild to moderate disease. In Colombia, during 2020, COVID-19 infections in children stayed below 9.2% of the total cases, with no trends for age group or sex. Objective: To estimate the incidence of acute respiratory symptoms and COVID-19 in children from public schools in Bogotá, Colombia during the second semester of 2020. Material and methods: A telephone survey was conducted in over 5,000 scholar children. Antecedents and use of health services were informed. Descriptive statistics were used. Results: A total of 151.470 persons per day accounting for an IR of 157,8 per 100,000 people; almost three times the rate reported by the official surveillance system in the city. Conclusion: A lack of diagnosis and consultation in children was found compared to the general population. Further research is needed to elucidate the true burden of the disease in children.

Introducción. Más del 90% de los niños infectados con COVID-19 en el mundo, desarrollaron enfermedad leve a moderada. En Colombia, durante el 2020, la infección del COVID-19 en niños se mantuvo por debajo de 9,2 % del total de los casos sin tendencias por grupo de edad o sexo. Objetivo. Estimar la incidencia de síntomas respiratorios agudos y COVID19 en niños de escuelas públicas en Bogotá (Colombia) durante el segundo semestre de 2020. Materiales y métodos. Se hizo una encuesta telefónica en más de 5.000 escolares. Se recolectó información de antecedentes médicos y uso de servicios de salud. La información obtenida se describió mediante estadística descriptiva. Resultados. Se contabilizó un total de 151.470 personas al día para una tasa de incidencia de 157,8 en 100.000 personas, casi tres veces la tasa reportada por el sistema de vigilancia oficial de la ciudad. Conclusión. Se encontraron deficiencias en el diagnóstico y consulta de los niños, al compararlos con la población general. Se necesita más investigación para dilucidar la verdadera carga de la enfermedad en la población infantil.

Antifibrotics and lung transplantation: A Spanish multicentre case-controlled study.

BACKGROUND AND OBJECTIVE: Antifibrotic drugs are the standard treatments for patients with idiopathic pulmonary fibrosis (IPF). This study aims to assess the safety of antifibrotic treatment in IPF patients undergoing lung transplantation. METHODS: Patients with a diagnosis of IPF who received a lung transplant between January 2015 and June 2019 at four Spanish hospitals specialized in lung transplantation were retrospectively recruited. Cases were defined as patients receiving antifibrotic treatments at time of transplant. Each case was matched with a control who did not receive antifibrotic treatment. RESULTS: A total of 164 patients were included in the study cohort (103 cases and 61 controls). There were no statistically significant differences between the cases and controls in any of the items studied related to transplantation except the time until the appearance of chest wall dehiscence: although there were no differences in the incidence of wall dehiscence in either group (12.3% vs. 13.7%; p = 0.318), the patients on antifibrotic drugs experienced it earlier (21 days [IQR = 12.5-41.5] vs. 63 days [IQR = 46.75-152.25]; p = 0.012). There were no differences in overall post-transplant survival between the two groups (p = 0.698) or in conditional survival at 30 days, 90 days, 3 years or 5 years. However, 1 year survival was significantly greater among controls (80.6% vs. 93.3%; p = 0.028). CONCLUSION: There was evidence that chest wall dehiscences appeared earlier post-transplant in patients using antifibrotics, even though this factor did not significantly impact survival.

Autoevaluación de competencias profesionales de enfermería, en un hospital público de tercer nivel en Guanajuato, México / Self-assessment of nursing professional competencies in a tertiary level public hospital in Guanajuato, Mexico

Resumen: Objetivo: Analizar la autoevaluación de las competencias profesionales de enfermería, en un hospital público de tercer nivel de atención, relacionadas con sus características laborales. Material y Métodos: Estudio cuantitativo, descriptivo correlacional, en 162 profesionales de enfermería de los servicios de hospitalización de un hospital público de tercer nivel de atención, se utilizó el instrumento validado "Competencias profesionales para licenciados en enfermería", con una confiabilidad de Alfa de Cronbach de 0.97, el estudio se apegó a lo estipulado en el Reglamento de la Ley General de Salud en Materia de Investigación. Resultados: De los profesionales de enfermería evaluados el 77.2% corresponde al sexo femenino; el rango de edad que predominó fue de 41- 45 años con 50.6%, en su mayoría casados (44.4 %). Destaca la antigüedad laboral de 11 a 14 años (48.1%) y el grado académico de Licenciatura (49.4%). El nivel global de competencias profesionales se ubicó en 164.8 (DE=11.4) de una puntuación máxima de 200, el indicador de ética destaca con una media de 33.85 (DE=2.88), seguido del indicador de atención integral con una media de 33.33 (DE=3.22). No se encontró relación estadísticamente significativa, entre las competencias profesionales del personal de enfermería y las características laborales. Conclusiones: El personal de enfermería, se percibe competente para brindar atención integral con apego ético; no obstante, se demanda fortalecer dimensiones como la educación, investigación y gestión, que contribuyan a la mejora continua de la calidad y seguridad en la atención.

Abstract: Objective: Analyze the self-assessment of the professional competencies of nurses in a tertiary care public hospital related to their work characteristics. Material and Methods: Quantitative, descriptive correlational study of 162 nursing professionals in the hospitalization services of a tertiary care public hospital, using the validated instrument "Professional competencies for nursing graduates", with a Cronbach's Alpha reliability of 0.97, the study complied with the stipulations of the Regulations of the General Law of Health on Research. Results: Of the nursing professionals evaluated, 77.2% were female; the predominant age range was 41-45 years with 50.6%, mostly married (44.4%). The most outstanding characteristics were seniority of 11 to 14 years (48.1 %) and a bachelor's degree (49.4 %). The overall level of professional competencies was 164.8 (SD=11.4) out of a maximum score of 200, the ethics indicator stands out with a mean of 33.85 (SD=2.88), followed by the comprehensive care indicator with a mean of 33.33 (SD=3.22). No statistically significant relationship was found between the professional competencies of the nursing staff and the work characteristics. Conclusions: The nursing staff is perceived as competent to provide comprehensive care with ethical attachment; however, there is a demand to strengthen dimensions such as education, research and management that contribute to the continuous improvement of quality and safety in care.

Bioinformatic Analysis of the Effect of Silver Nanoparticles on Colorectal Cancer Cell Line.

Colorectal cancer (CRC) is the most diagnosed cancer with the highest mortality rate each year globally. Although there are treatments for CRC, the development of resistance to therapies decreases the success of treatments. In vitro studies using the Caco-2 cell line have revealed the anticancer properties of silver nanoparticles (AgNPs) as a possible treatment for this disease. This study considered four researches that evaluated the proteomic profiles of cells of the Caco-2 line exposed to AgNPs. We performed a bioinformatics analysis to predict protein-protein interaction, hub genes, Gene Ontology (molecular function, biological process, and cellular components), KEGG pathways, analysis of expression, and immune cell infiltration. For these analyses, the STRING, DAVID, UALCAN, GEPIA2, and TISIDB databases were used. The results in Gene Ontology show that AgNPs cause a deregulation of genes related to cell-cell adhesion, the cytoplasm, the centriole, and carbon metabolism. Hub genes were identified, including GADPH, ENO1, EEF2, and ATP5A1, which showed differential expression in patients with adenocarcinoma of the colon and rectum. Additionally, the expression of the hub genes and immune cells was correlated. It was found that ATP5A1 and ENO1 were positively correlated with the infiltration of CD4+ T lymphocytes in colon adenocarcinoma and a negative correlation between GADPH and PDIA3 with the infiltration of NK cells and CD4+ T lymphocytes in rectal adenocarcinoma, respectively. In conclusion, the administration of AgNPs causes an alteration of biological processes, cellular components, metabolic pathways, deregulation of hub genes, and the activity of immune cells leading to a potential anticancer effect.

Relation of serum IL-32 levels and gene polymorphism rs45499297 with obesity in Mexican patients: a laboratory and in silico analysis.

Introduction: Background: many genes have been involved in the development of obesity. Interleukin 32 (IL-32) is a proinflammatory cytokine; rs45499297 is a T/C promoter, single-nucleotide polymorphism of the IL32 gene. Objectives: this study aimed to evaluate the rs45499297 polymorphism and its association with obesity. Another objective of this study was to carry out an in silico analysis. Methods: this study was cross-sectional, and included 333 subjects classified by body mass index and fat percentage. The plasma glucose and lipid profile were measured. We measured serum IL-32 protein by ELISA and the rs45499297 polymorphism by PCR-RFLP. We used several databases to build the IL32 gene network and infer transcription factors that bind to this polymorphic site. Results: subjects underweight and with low fat percentages had lower levels of IL-32. CT genotype and allele C were less frequent in the overweight/obesity group than in the normal-weight group. Interestingly, this result remained only in the male gender. We found that the transcription factors Hepatocyte Nuclear Factor and Specificity Protein 1 bind to this polymorphic site. In addition, we infer that IL32 is involved in metabolic pathways related to viral infections. Conclusion: the TC genotype is associated with overweight/obesity. The decrease in levels of IL-32 observed in underweight and low fat percentage groups could be due to an impaired inflammatory profile. The in silico analysis showed that several transcriptional factors bind at this polymorphic site, and that the enrichment of the metabolic pathways is diverse.

Introducción: Introducción: la interleucina 32 es una citocina proinflamatoria. El rs45499297 es un polimorfismo de nucleótido simple del gen de IL32, situado en la región promotora y caracterizado por un cambio de T/C. Objetivo: evaluar el polimorfismo rs45499297 y su asociación con la obesidad, y realizar un análisis in silico. Métodos: el estudio fue transversal e incluyó 333 sujetos clasificados por índice de masa corporal y porcentaje de grasa. Se midieron la glucosa y el perfil lipídico, así como los niveles séricos de IL-32 mediante ELISA y el genotipo del polimorfismo rs45499297 mediante PCR-RFLP. Para el análisis in silico se utilizaron varias bases de datos para hacer la red de genes de IL32 e inferir factores de transcripción unidos al sitio polimórfico. Resultados: los sujetos con bajo peso y bajo porcentaje de grasa tienen niveles más bajos de IL-32. El genotipo TC y el alelo C se encontraron con menos frecuencia en los sujetos con sobrepeso/obesidad que en los normopeso, resultado que permaneció solo en el género masculino. Se encontró que el factor nuclear de los hepatocitos y la proteína de especificidad 1 se unen a este sitio polimórfico. Se infiere que IL32 está involucrado en vías metabólicas relacionadas con las infecciones virales. Conclusión: el genotipo TC está asociado al sobrepeso/la obesidad. La disminución de los niveles de IL-32 observada en los sujetos con bajo peso y bajo porcentaje de grasa podría ser por un perfil inflamatorio alterado. El análisis in silico mostró que varios factores de transcripción se unen al sitio polimórfico y que el enriquecimiento de las vías metabólicas es diverso.

Total mercury exposure risk and selenium content measuring on fishery products consumed by women of childbearing age from Bogota, Colombia / Riesgo de exposición a mercurio total y medición del contenido de selenio en productos de la pesca consumidos por mujeres en edad fértil de Bogotá, Colombia

Background: Dietary exposure to mercury in women of childbearing age could result in neurological effects on the fetus. A health risk assessment of total mercury by fishery products intake has not been conducted in this population group in Bogota, Colombia. On the other hand, it has been suggested that selenium content on fishery products may have a protective effect against mercury toxicity. Nevertheless, selenium content on fish species marketed in Bogota has not been determined. Objective: Exposure risk to total mercury and selenium content on fishery products consumed by women of childbearing age from Bogota, Colombia, were assessed. Methods: Total mercury and selenium concentrations for products available at fish stores and supermarkets were determined. The exposure risk to total mercury was estimated considering the intake of these products by women of childbearing age group. Results: Total mercury highest concentrations were 0.8166 mg/kg in mota (Calophysusmacropterus), and 0.6275 mg/kg in catfish (Pseudoplatystoma tigrinum). On the other hand, the highest selenium concentration was 0.6471 mg/kg in nicuro (Pimelodus blochii). Finally, it was established that for women of childbearing age group, health risk of exposure to total mercury due to mota intake exceeded by 8.56-fold the reference dose. Conclusions:Mota intake considerably increases exposure risk to total mercury on women of childbearing age from Bogota, Colombia. The selenium levels established in the fishery products assessed, except for catfish and mota, are theoretically suggestive of a protective effect of selenium against mercury toxicity. Consequently, continuous total mercury concentrations monitoring is required to protect health of women of childbearing age and the general population from Bogota, Colombia

Antecedentes: La exposición dietética al mercurio en mujeres en edad fértil podría provocar efectos neurológicos en el feto. En Bogotá, Colombia no se han realizado evaluaciones de riesgo por la exposición al mercurio total debido a la ingesta de productos de la pesca en este grupo de la población. Por otro lado, ha sido sugerido que el contenido de selenio en los productos de la pesca podría tener un efecto protector frente a la toxicidad por mercurio, sin embargo, el contenido de selenio en las especies de peces comercializadas en Bogotá, Colombia no ha sido determinado. Objetivo: Evaluar el riesgo de exposición al mercurio total y el contenido de selenio en los productos de la pesca consumidos por las mujeres en edad fértil de Bogotá, Colombia. Métodos: Se determinaron las concentraciones de mercurio total y selenio en distintos productos de la pesca disponibles en pescaderías y supermercados. El riesgo de exposición a mercurio total se estimó considerando la ingesta de estos productos por parte de un grupo de mujeres en edad fértil. Resultados: Las concentraciones más altas de mercurio total fueron de 0.8166 mg/kg en mota (Calophysus macropterus) y 0.6275 mg/kg en bagre (Pseudoplatystoma tigrinum). Por otro lado, la concentración más alta de selenio fue de 0.6471 mg/kg en nicuro (Pimelodus blochii). Finalmente, se estableció que el riesgo de exposición a mercurio total, debido a la ingesta de mota, excedió en 8.56 veces la dosis de referencia en el grupo de mujeres en edad fértil. Conclusiones: La ingesta de mota aumenta el riesgo de exposición al mercurio total en las mujeres en edad fértil de Bogotá, Colombia. Por otro lado, los niveles de selenio identificados en los productos evaluados, excepto en bagre y mota, teóricamente sugieren un posible efecto protector del selenio contra la toxicidad por mercurio. Considerando lo indicado, es necesario realizar un monitoreo continuo de las concentraciones de mercurio total en los productos de la pesca, con el fin de proteger la salud de las mujeres en edad fértil y de la población general de Bogotá, Colombia

Tumour necrosis factor-alpha polymorphism -308 G/a and its protein in subjects with gingivitis.

OBJECTIVE: This study examined the association between tumour necrosis factor-alpha (TNF- α) (-308 G/A) polymorphism and gingivitis, and serum and salivary TNF- α levels, in a Mexican population. MATERIAL AND METHODS: This study enrolled 171 subjects, divided into two groups: healthy subjects and gingivitis patients. TNF- α (-308 G/A) gene polymorphism was analyzed by PCR-RFLP assay. Salivary and serum samples were used to measure cytokine levels through the ELISA technique. RESULTS: TNF- α (-308 G/A) polymorphism was shown to have a protective effect in carriers of the A/A genotype and allele A. The G/A genotype is associated with an increase in high-density lipoprotein cholesterol (HDL-C) levels in the gingivitis group. Healthy individuals had higher levels of salivary TNF- α and HDL-C, and increased salivary flow. Triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels were increased in the gingivitis group. No statistical differences were found in serum TNF- α levels. CONCLUSION: Our data demonstrate that the TNF- α -308 A/A genotype exerts a protective effect against gingivitis. Moreover, oral conditions are associated with some biochemical parameters.

Factores asociados a complicaciones en pacientes diabéticos con enfermedad coronaria multivaso intervenidos quirúrgicamente en un centro cardiovascular de alta complejidad / Factors associated with complications in diabetic patients with multivessel coronary disease surgically operated in a highly complex cardiovascular center

Resumen Objetivo: Determinar las características sociodemográficas, clínicas y de procedimiento asociadas a complicaciones en pacientes diabéticos con enfermedad coronaria severa, sometidos a revascularización quirúrgica. Métodos: Estudio de cohortes retrospectivo en pacientes mayores de 18 años con diagnóstico de diabetes mellitus y enfermedad coronaria multivaso, sometidos a revascularización quirúrgica, en el que se evaluaron las características individuales, clínicas y de procedimiento asociadas a complicaciones posquirúrgicas. Se realizó un análisis bivariado y multivariado mediante regresión logística binaria. Resultados: Los factores asociados a complicaciones fueron edad, índice de masa corporal, fracción de eyección del ventrículo izquierdo, clase funcional de la Asociación del Corazón de Nueva York (NYHA, su sigla en inglés por New York Heart Association) preintervención y antecedente de consumo de alcohol y tabaco; de estos, la edad es la variable que persiste con significancia estadística tras el modelo de regresión logística binaria. Conclusión: La incidencia de complicaciones posoperatorias en pacientes diabéticos sometidos a revascularización quirúrgica es comparable con la observada en estudios previos, y el factor asociado encontrado para este grupo de pacientes es la edad. El modelo podría explicar el 23 % del desarrollo de complicaciones en la cohorte estudiada.

Abstract Objective: To determine the sociodemographic, clinical and procedural characteristics associated with complications in diabetic patients with severe coronary disease treated by coronary artery bypass surgery. Methods: A retrospective cohort study in patients over 18 years old with a diagnosis of diabetes mellitus and multivessel coronary disease, undergoing surgical revascularization, where individual, clinical and procedural characteristics associated with surgical complications were evaluated. A bivariate and multivariate analysis was performed using binary logistic regression. Results: The factors associated with complications that were found were: age, body mass index, left ventricular ejection fraction, pre intervention New York Heart Association (NYHA) functional class, alcohol and tobacco history. Of these, age was the only variable that persists with statistical significance after the logistic regression model. Conclusion: The incidence of postoperative complications in diabetic patients undergoing surgical revascularization is comparable to that observed in previous studies. The associated factor found for this group of patients is the age.

DNA repair pathways are altered in neural cell models of frataxin deficiency.

Friedreich's ataxia (FRDA) is a hereditary and predominantly neurodegenerative disease caused by a deficiency of the protein frataxin (FXN). As part of the overall efforts to understand the molecular basis of neurodegeneration in FRDA, a new human neural cell line with doxycycline-induced FXN knockdown was established. This cell line, hereafter referred to as iFKD-SY, is derived from the human neuroblastoma SH-SY5Y and retains the ability to differentiate into mature neuron-like cells. In both proliferating and differentiated iFKD-SY cells, the induction of FXN deficiency is accompanied by increases in oxidative stress and DNA damage, reduced aconitase enzyme activity, higher levels of p53 and p21, activation of caspase-3, and subsequent apoptosis. More interestingly, FXN-deficient iFKD-SY cells exhibit an important transcriptional deregulation in many of the genes implicated in DNA repair pathways. The levels of some crucial proteins involved in DNA repair appear notably diminished. Furthermore, similar changes are found in two additional neural cell models of FXN deficit: primary cultures of FXN-deficient mouse neurons and human olfactory mucosa stem cells obtained from biopsies of FRDA patients. These results suggest that the deficiency of FXN leads to a down-regulation of DNA repair pathways that synergizes with oxidative stress to provoke DNA damage, which may be involved in the pathogenesis of FRDA. Thus, a failure in DNA repair may be considered a shared common molecular mechanism contributing to neurodegeneration in a number of hereditary ataxias including FRDA.

Neuronal modulation of hepatic lipid accumulation induced by bingelike drinking.

Excessive alcohol consumption, including binge drinking, is a common cause of fatty liver disease. Binge drinking rapidly induces hepatic steatosis, an early step in the pathogenesis of chronic liver injury. Despite its prevalence, the process by which excessive alcohol consumption promotes hepatic lipid accumulation remains unclear. Alcohol exerts potent effects on the brain, including hypothalamic neurons crucial for metabolic regulation. However, whether or not the brain plays a role in alcohol-induced hepatic steatosis is unknown. In the brain, alcohol increases extracellular levels of adenosine, a potent neuromodulator, and previous work implicates adenosine signaling as being important for the development of alcoholic fatty liver disease. Acute alcohol exposure also increases both the activity of agouti-related protein (AgRP)-expressing neurons and AgRP immunoreactivity. Here, we show that adenosine receptor A2B signaling in the brain modulates the extent of alcohol-induced fatty liver in mice and that both the AgRP neuropeptide and the sympathetic nervous system are indispensable for hepatic steatosis induced by bingelike alcohol consumption. Together, these results indicate that the brain plays an integral role in alcohol-induced hepatic lipid accumulation and that central adenosine signaling, hypothalamic AgRP, and the sympathetic nervous system are crucial mediators of this process.

Determinación de intervalos biológicos de referencia para adultos en el equipo hematológico BC-5000 de la Escuela de Microbiología de la Universidad de Antioquia, Medellín 2017 / Determination of reference biological intervals in a hematology analyzer BC-5000 of the Microbiology School of the University of Antioquia, Medellin 2017

RESUMEN Introducción: los valores del hemograma en adultos pueden variar de acuerdo con factores como el origen étnico, la edad, el sexo y la altura sobre el nivel del mar, por lo cual es indispensable conocer intervalos biológicos asociados a nuestra población. Por esto el objetivo de nuestro estudio fue determinar intervalos biológicos de referencia (IBR) para adultos en un equipo hematológico BC-5000. Metodología: estudio descriptivo transversal con 111 donantes entre 18 y 62 años de un banco de sangre de Medellín. Se realizó un hemograma, proteína C reactiva y ferritina. Se calcularon los IBR siguiendo las recomendaciones de la Federación Internacional de Química Clínica. La comparación de los IBR según sexo se realizó con la prueba T-student. Resultados: los IBR calculados mediante la fórmula X ± (DS * 1,96) mostraron diferencias estadísticamente significativas entre hombres y mujeres para el recuento de la mayoría de los parámetros. Se obtuvieron medias estadísticas mayores en mujeres para el recuento de leucocitos y plaquetas, recuentos absolutos y relativos de algunas células blancas, volumen plaquetario medio (VPM) y plaquetocrito (PCT). Discusión: la presencia de andrógenos en el sexo masculino, inductores del sistema eritropoyético, así como los estrógenos y el período menstrual, supresores del mismo, pueden explicar los valores menores en el recuento eritrocitario, en los rangos de hemoglobina, hematocrito y glóbulos rojos en las mujeres. Las altas cargas de estrógenos e interleucinas 6 y 10 en las mujeres amplían la vida media de células como linfocitos, explicando la diferencia en el recuento leucocitario a expensas de linfocitos encontrados en el presente estudio.

SUMMARY Introduction: The adult hemogram values can vary according factors such as ethnic origin, age, sex and level above the sea, whereby it is essential to know the biological intervals associated to our own population. Therefore, the objective of our study was to determine biological reference intervals (BRI) for adults with the hematological equipment BC-5000. Methods: This is a transversal descriptive study with 111 blood bank donors from Medellín, between 18 62 years old. Hemogram, Creactive protein and ferritin were done. The BRI were calculated according to the recommendations of the International Federation of Clinical Chemistry (IFCC), with the formula X ± (DS * 1, 96). BRI comparison according sex was carried out with the t-student test. Results: Calculated BRI by X ± (DS * 1, 96) formula, showed statistically significant differences (P < 0, 05) between men and women for count in most of the parameters. Higher statistical means were obtain in women for the count of leukocytes and platelets, absolute counts of some white cells, VPN y PCT. Discussion: The presence of androgens in the male sex, inductors of the erythropoiesis system, as well as the estrogens and menstrual period, suppressor of this system, can explain the lower values in the female erythrocyte count, the hemoglobin, hematocrit and red cell lower ranges. The high estrogen and interleukins 6 and 1 loads in women, drive the extended half-life of some cells like lymphocytes, that can explain the difference in leucocyte count found in the present study.

Newborn cystic fibrosis screening in southeastern Mexico: Birth prevalence and novel CFTR gene variants.

OBJECTIVE: To use the results of the first five years of a cystic fibrosis newborn screening program to estimate the cystic fibrosis birth prevalence and spectrum of cystic fibrosis transmembrane conductance regulator ( CFTR) gene variants in Yucatan, Mexico. METHODS: Screening was performed from 2010 to 2015, using two-tier immunoreactive trypsinogen testing, followed by a sweat test. When sweat test values were >30 mmol/L, the CFTR gene was analyzed. RESULTS: Of 96,071 newborns screened, a second sample was requested in 119 cases. A sweat test was performed in 30 newborns, and 9 possible cases were detected (seven confirmed cystic fibrosis and two inconclusive). The most frequently detected CFTR pathogenic variant (5/14 cystic fibrosis alleles, 35.7%) was p.(Phe508del); novel p.(Ala559Pro) and p.(Thr1299Hisfs*29) pathogenic variants were found. CONCLUSIONS: Cystic fibrosis birth prevalence in southeastern Mexico is 1:13,724 newborns. Immunoreactive trypsinogen blood concentration is influenced by gestational age and by the time of sampling. The spectrum of CFTR gene variants in Yucatan is heterogeneous.