The impact of comorbidity status in COVID-19 vaccines effectiveness before and after SARS-CoV-2 omicron variant in northeastern Mexico: a retrospective multi-hospital study.

Introduction: The end of the coronavirus disease 2019 (COVID-19) pandemic has been declared by the World Health Organization on May 5, 2023. Several vaccines were developed, and new data is being published about their effectiveness. However, the clinical trials for the vaccines were performed before the Omicron variant appeared and there are population groups where vaccine effectiveness still needs to be tested. The overarching goal of the present study was to analyze the effects of COVID-19 vaccination before and after the Omicron variant in patients considering comorbidities in a population from Nuevo Leon, Mexico. Methods: Epidemiological COVID-19 data from the Mexican Social Security Institute were collected from 67 hospitals located in northeastern Mexico, from July 2020 to May 2023, and a total of 669,393 cases were compiled, 255,819 reported a SARS-CoV-2 positive reverse transcription quantitative polymerase chain reaction (RT-qPCR) test or a positive COVID-19 antigen rapid test. Results: Before Omicron (BO, 2020-2021), after 14 days of two doses of COVID-19 vaccine, BNT162b2 and ChAdOx1 vaccines were effective against infection in non-comorbid and all comorbid subgroups, whereas after Omicron (AO, 2022- 2023) there was no significant effectiveness against infection with none of the vaccines. Regarding hospitalization BO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 significantly protected non-comorbid patients whereas BNT162b2, ChAdOx1, and mRNA-1273, protected all comorbid subgroups against hospitalization. AO, BNT162b2, ChAdOx1, CoronaVac and mRNA-1273 were effective against hospitalization in non-comorbid patients whereas for most comorbid subgroups BNT162b2, ChAdOx1 and CoronaVac were effective against hospitalization. Non-comorbid patients were protected against death as an outcome of COVID-19 during the BO period with most vaccines whereas a reduction in effectiveness was observed AO with mRNA-1273 vaccines in patients with hypertension, and diabetes mellitus. Discussion: BO, COVID-19 vaccines were effective against infection, hospitalization, and death whereas AO, COVID-19 vaccines failed to protect the population from COVID-19 infection. A varying effectiveness against hospitalization and death is observed AO.

Mechanistic Insights about Sorafenib-, Valproic Acid- and Metformin-Induced Cell Death in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is among the main causes of death by cancer worldwide, representing about 80-90% of all liver cancers. Treatments available for advanced HCC include atezolizumab, bevacizumab, sorafenib, among others. Atezolizumab and bevacizumab are immunological options recently incorporated into first-line treatments, along with sorafenib, for which great treatment achievements have been reached. However, sorafenib resistance is developed in most patients, and therapeutical combinations targeting cancer hallmark mechanisms and intracellular signaling have been proposed. In this review, we compiled evidence of the mechanisms of cell death caused by sorafenib administered alone or in combination with valproic acid and metformin and discussed them from a molecular perspective.

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.

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.

Sex, Age, and Comorbidities Are Associated with SARS-CoV-2 Infection, COVID-19 Severity, and Fatal Outcome in a Mexican Population: A Retrospective Multi-Hospital Study.

People with comorbidities and the male sex are at a higher risk of developing severe COVID-19. In the present study, we aim to investigate the associated factors for infection, severity, and death due to COVID-19 in a population from Nuevo León, México. Epidemiological COVID-19 data were collected from 65 hospitals from December 2020 to May 2022. A total of 75,232 cases were compiled from which 25,722 cases were positive for SARS-CoV-2. Male sex, older age, diabetes, obesity, and hypertension were associated with infection. In addition to the above-mentioned factors, renal disease, cardiovascular disease, and immunosuppression were found to be associated with increased COVID-19 severity. These factors, as well as neurological diseases, are also associated with death due to COVID-19. When comparing the different variants of SARs-CoV-2, the variant B1.1.519 increased the probability of death by 2.23 times compared to the AY.20 variant. Male sex, older age, diabetes, obesity, and hypertension are associated with SARS-CoV-2 infection, severity, and death. Along with the aforementioned comorbidities, renal disease, cardiovascular disease, and immunosuppression are also associated with severity and death. Another factor associated with death is the presence of neurological disease. The SARS-CoV-2 B1.1.519 variant increases the odds of death compared to the SARS-CoV-2 AY.20 variant.

Fear and Coping with Death in Intensive Care Nurses: a Structural Model Predictor of Compassion Fatigue.

OBJECTIVES: To determine the effect of fear and coping with death on compassion fatigue in nurses working in the intensive care unit. METHODS: Correlational-predictive design, applied in 245 nurses working in the intensive care unit through intentional sampling. The study applied a personal data card, the Collet-Lester Fear of Death Scale (α=0.72), the Bugen Fell of Death Scale (α=0.82), and the Empathy Exhaustion Scale (α=0.80). Descriptive and inferential statistics were performed, such as Spearman's test and a structural equation model. RESULTS: The work had 255 nurses who participated, finding a relationship among fear and coping toward death and compassion fatigue (p<0.01), together with the equation model showing that fear and coping toward death have a positive effect in 43.6% on compassion fatigue. CONCLUSIONS: Fear and coping with death have an effect on compassion fatigue in nurses working in the intensive care unit, so that when working in a critical area it can cause health effects.

Cell-type dependent regulation of pluripotency and chromatin remodeling genes by hydralazine.

BACKGROUND: The generation of induced pluripotent stem cells has opened the field of study for stem cell research, disease modeling and drug development. However, the epigenetic signatures present in somatic cells make cell reprogramming still an inefficient process. This epigenetic memory constitutes an obstacle in cellular reprogramming. Here, we report the effect of hydralazine (HYD) and valproic acid (VPA), two small molecules with proven epigenetic activity, on the expression of pluripotency genes in adult (aHF) and neonatal (nbHF) human fibroblasts. METHODS: aHF and nbHF were treated with HYD and/or VPA, and viability and gene expression assays for OCT4, NANOG, c-MYC, KLF4, DNMT1, TET3, ARID1A and ARID2 by quantitative PCR were performed. aHF and nbHF were transfected with episomal plasmid bearing Yamanaka factors (OCT4, SOX2, KLF4 and c-MYC) and exposed to HYD and VPA to determine the reprogramming efficiency. Methylation sensitive restriction enzyme (MSRE) qPCR assays were performed on OCT4 and NANOG promoter regions. Immunofluorescence assays were carried out for pluripotency genes on iPSC derived from aHF and nbHF. RESULTS: HYD upregulated the expression of OCT4 (2.5-fold) and NANOG (fourfold) genes but not c-Myc or KLF4 in aHF and had no significant effect on the expression of all these genes in nbHF. VPA upregulated the expression of NANOG (twofold) in aHF and c-MYC in nbHF, while it downregulated the expression of NANOG in nbHF. The combination of HYD and VPA canceled the OCT4 and NANOG overexpression induced by HYD in aHF, while it reinforced the effects of VPA on c-Myc expression in nbHF. The HYD-induced overexpression of OCT4 and NANOG in aHDF was not dependent on demethylation of gene promoters, and no changes in the reprogramming efficiency were observed in both cell populations despite the downregulation of epigenetic genes DNMT1, ARID1A, and ARID2 in nbHF. CONCLUSIONS: Our data provide evidence that HYD regulates the expression of OCT4 and NANOG pluripotency genes as well as ARID1A and ARID2 genes, two members of the SWI/SNF chromatin remodeling complex family, in normal human dermal fibroblasts.

Fear and Coping with Death in Intensive Care Nurses: a Structural Model Predictor of Compassion Fatigue / Miedo y afrontamiento ante la muerte del usuario: un modelo estructural predictor de la fatiga por compasión en enfermeros de cuidados intensivos / Medo e enfrentamento da morte do usuário: um modelo estrutural preditivo da fadiga por compaixão em enfermeiros de terapia intensiva

Objective. To determine the effect of fear and coping with death on compassion fatigue in nurses working in the intensive care unit. Methods. Correlational-predictive design, applied in 245 nurses working in the intensive care unit through intentional sampling. The study applied a personal data card, the Collet-Lester Fear of Death Scale (α=0.72), the Bugen Fell of Death Scale (α=0.82), and the Empathy Exhaustion Scale (α=0.80). Descriptive and inferential statistics were performed, such as Spearman's test and a structural equation model. Results. The work had 255 nurses who participated, finding a relationship among fear and coping toward death and compassion fatigue (p<0.01), together with the equation model showing that fear and coping toward death have a positive effect in 43.6% on compassion fatigue. Conclusion. Fear and coping with death have an effect on compassion fatigue in nurses working in the intensive care unit, so that when working in a critical area it can cause health effects

Objetivo. Determinar el efecto del miedo y afrontamiento ante la muerte sobre la fatiga por compasión en enfermeros que laboran en la unidad cuidados intensivos. Método. Diseño correlacional-predictivo. A través de un muestreo intencional se seleccionaron 255 enfermeros que laboraban en Unidades de Cuidados Intensivos de Adultos de hospitales de la Península de Yucatán (México). Se aplicó una cédula de datos personales, la escala de miedo a la muerte de Collet-Lester (α=0.72), la escala de Bugen de afrontamiento de la muerte (α=0.82) y la escala de agotamiento por empatía (α=0.80). Se realizó estadística descriptiva e inferencial como prueba de Spearman y un modelo de ecuación estructural. Resultados. Se encontró relación del miedo y el afrontamiento hacia la muerte con la fatiga por compasión (p<0.01). Adicionalmente, el modelo de ecuaciones muestra que el miedo y el afrontamiento hacia la muerte predice en un 43.6% sobre la fatiga por compasión. Conclusión. El miedo y el afrontamiento hacia la muerte tienen efecto sobre la fatiga por compasión en los enfermeros que laboran en la unidad de cuidados intensivos, por lo que al estar laborando en esta área crítica puede provocar afectaciones en su estado de salud.

Objetivo. Determinar o efeito do medo e enfrentamento da morte na fadiga por compaixão em enfermeiros que atuam em Unidade de Terapia Intensiva (UTI). Métodos. Desenho preditivo correlacional. Por meio de amostragem intencional, foram selecionados 255 enfermeiros que trabalhavam em Unidades de Terapia Intensiva de Adultos de hospitais da Península de Yucatán (México). Foi aplicada uma ficha de dados pessoais, a escala de medo da morte de Collet -Lester (α=0.72), a escala de Bugen de enfrentamento da morte (α=0.82) e a escala de exaustão por empatia (α=0.80). Foram realizadas estatísticas descritivas e inferenciais como o teste de Spearman e um modelo de equação estrutural. Resultados. Encontrou-se relação entre medo e enfrentamento da morte e fadiga por compaixão (p<0.01). Além disso, o modelo de equação mostra que o medo e o enfrentamento da morte preveem 43.6% da fadiga por compaixão. Conclusão. O medo e o enfrentamento da morte afetam a fadiga por compaixão em enfermeiros que atuam em UTI, portanto, trabalhar nessa área crítica pode afetar seu estado de saúde.

Hypertrophic cardiomyopathy in a patient with secondary hypoparathyroidism: A case report.

Parathyroid hormone (PTH) has direct and indirect actions on cardiovascular cells. The effects of chronic hypoparathyroidism on cardiac morphology, function, and conduction are still unclear. Low PTH states are associated with multiple manifestations in the heart, acute or chronic. Acute hypocalcemic cardiomyopathy is a transient dilated cardiomyopathy with reduced ejection fraction and diffuse left ventricular hypokinesia. Chronic hypoparathyroidism-associated cardiomyopathy is a rare disease that may cause reduced myocardial tension, cardiac cavity enlargement, arrhythmias, and congestive heart failure. Here, we describe a 73-year-old woman with chronic hypoparathyroidism and hypocalcemia, who developed a hypertrophic cardiomyopathy, and not a dilated hypocalcemia-associated cardiomyopathy, which would be usually the case.

Caracterización de pacientes con traumatismos torácicos atendidos en el servicio de Cirugía General. Cienfuegos, 2019-2020 / Characterization of patients with thoracic trauma treated in the General Surgery Service. Cienfuegos, 2019-2020

RESUMEN Fundamento el traumatismo torácico es un cuadro clínico complejo que puede comprometer la vida del paciente. Por ello es de interés su estudio y análisis. Objetivo caracterizar los pacientes con traumatismo torácico en el servicio de Cirugía General. Métodos estudio descriptivo, prospectivo, de serie de casos, que incluyó a pacientes que ingresaron con el diagnóstico de traumatismo torácico, en el servicio de Cirugía General del Hospital General Universitario Dr. Gustavo Aldereguía Lima, de Cienfuegos, en el período enero/2019 a diciembre/2020. Las variables analizadas fueron: edad, sexo, comorbilidades, exámenes imagenológicos, agente causal, lesión torácica, tipo de tratamiento, tipo de traumatismo torácico y estado al egreso. Resultados el trauma de tórax fue más frecuente en el sexo masculino, a partir de la cuarta década de vida en pacientes sanos. El examen imagenológico más usado fue la radiografía simple de tórax; y el agente causal predominante, la herida por arma blanca. Las lesiones torácicas más frecuentes resultaron el enfisema subcutáneo y el hemoneumotorax, así como la pleurostomía fue el tipo de tratamiento más usado. Predominó el traumatismo torácico aislado, siendo las lesiones abdominales las más asociadas. La mayoría de los pacientes egresaron vivos. Conclusión el trauma torácico constituye una patología altamente desafiante, por lo complejas que pueden llegar a ser las lesiones derivadas de él; se presenta con mayor frecuencia en hombres sanos. Cuando se asocia a otras lesiones aumenta la mortalidad.

Background chest trauma is a complex clinical picture that can compromise the patient's life. Therefore, its study and analysis is of interest. Objective to characterize patients with chest trauma in the General Surgery service. Methods descriptive, prospective, case series study which included patients admitted with a diagnosis of chest trauma, in the General Surgery Service at the Dr. Gustavo Aldereguía Lima General University Hospital, Cienfuegos, from January 2019 to December2020. The analyzed variables were: age, sex, comorbidities, imaging tests, causal agent, chest injury, type of treatment, type of chest trauma, and discharge status. Results chest trauma was more frequent in males, from the fourth decade of life in healthy patients. The most used imaging test was the simple chest X-ray; and the predominant causal agent, the stab wound. The most frequent chest injuries were subcutaneous emphysema and hemopneumothorax, and pleurostomy was the most used type of treatment. Isolated chest trauma prevailed, with abdominal injuries being the most associated. Most of the patients were discharged alive. Conclusion thoracic trauma constitutes a highly challenging pathology, due to how complex the injuries derived from it can become; It occurs more frequently in healthy men. When associated with other injuries, mortality increases.

Bilateral striopallidal calcinosis secondary to systemic lupus erythematosus.

Bilateral symmetric striatopallidal calcinosis with or without deposits in dentate nucleus, thalamus, and white matter is reported in patients ranging from asymptomatic, metabolic, toxic, and genetic autosomal dominant, familial or sporadic forms. Of the connective tissue diseases, it has been reported in very few cases in patients with systemic lupus erythematosus, many incorrectly labeled as Fahr syndrome without even having hypoparathyroidism. Here we describe a 30-year-old female patient with neuropsychiatric systemic lupus erythematosus manifested at diagnosis with mood disorders and anxiety, and 1-year later develops Lupus headache; Incidentally, an aneurism of the right middle cerebral artery and bilateral and symmetric calcifications of the caudate and lenticular nuclei were noted; this finding is a rarely reported manifestation of neuropsychiatric systemic lupus erythematosus. A review of the literature based on this case was carried out in electronic databases. There are approximately 29 patients reported in the literature, with calcifications in the basal ganglia associated with systemic lupus erythematosus occurs almost exclusively in young women (96.5%) with a mean age of 33.36 years (2 months-76 years), with a race predilection for Asians (65.5%). Regarding the neuropsychiatric syndromes defined by the American College of Rheumatology, the most frequently associated are movement disorders; followed by cognitive dysfunction, seizure disorders, mood disorders, cerebrovascular disease, psychosis, and acute confusional state, transverse myelitis, and demyelinating syndrome. The mean duration time of the SLE to detection of the basal ganglia calcification is 7.62 years (3 days-31 years).

Two New Dihydrosphingosine Analogs Against Mycobacterium tuberculosis Affect gltA1, lprQ, and rpsO Expression.

The emergence of multidrug-resistant (MDR) Mycobacterium tuberculosis strains threaten the control of tuberculosis. New antitubercular dihydrosphingosine analogs, named UCIs, have been evaluated in preclinical studies but their cellular and molecular mechanisms of action against M. tuberculosis are still unknown. The aim of this study was to evaluate the effect of UCI exposure on gene expression of drug-sensitive H37Rv and MDR CIBIN:UMF:15:99 clones of M. tuberculosis which were isolated, phenotypically, and genetically characterized, cultured to log phase and treated with UCI compounds; followed by total RNA isolation, reverse transcription and hybridization assays on Affymetrix genomic microarrays. Data were validated with RT-qPCR assays. As results, UCI-05 and UCI-14 exposure increased gltA1 expression in drug-sensitive H37Rv clones. Furthermore, UCI-05 increased lprQ expression in MDR CIBIN:UMF:15:99 M. tuberculosis clones while UCI-14 reduced the expression of this gene in drug-sensitive H37Rv clones. In addition, UCI-05 reduced rpsO expression in drug-sensitive H37Rv clones. We found gene expression alterations that suggest these molecules may alter carbon and lipid metabolism as well as interfere in the protein-producing machinery in M. tuberculosis.

Isotretinoin and Thalidomide Down-Regulate c-MYC Gene Expression and Modify Proteins Associated with Cancer in Hepatic Cells.

Hepatocellular carcinoma (HCC) is the most common form of liver cancer. The number of cases is increasing and the trend for the next few years is not encouraging. HCC is usually detected in the advanced stages of the disease, and pharmacological therapies are not entirely effective. For this reason, it is necessary to search for new therapeutic options. The objective of this work was to evaluate the effect of the drugs isotretinoin and thalidomide on c-MYC expression and cancer-related proteins in an HCC cellular model. The expression of c-MYC was measured using RT-qPCR and western blot assays. In addition, luciferase activity assays were performed for the c-MYC promoters P1 and P2 using recombinant plasmids. Dose-response-time analyses were performed for isotretinoin or thalidomide in cells transfected with the c-MYC promoters. Finally, a proteome profile analysis of cells exposed to these two drugs was performed and the results were validated by western blot. We demonstrated that in HepG2 cells, isotretinoin and thalidomide reduced c-MYC mRNA expression levels, but this decrease in expression was linked to the regulation of P1 and P1-P2 c-MYC promoter activity in isotretinoin only. Thalidomide did not exert any effect on c-MYC promoters. Also, isotretinoin and thalidomide were capable of inducing and repressing proteins associated with cancer. In conclusion, isotretinoin and thalidomide down-regulate c-MYC mRNA expression and this is partially due to P1 or P2 promoter activity, suggesting that these drugs could be promising options for modulating the expression of oncogenes and tumor suppressor genes in HCC.

NAT2 polymorphisms associated with the development of hepatotoxicity after first-line tuberculosis treatment in Mexican patients: From genotype to molecular structure characterization.

BACKGROUND AND AIMS: To assess the relevance of the slow acetylator phenotype based on NAT2 genotypes, among patients with pulmonary tuberculosis (PTB) that developed hepatotoxicity after first-line tuberculosis treatment in a Northeastern Mexican population. METHODS: Ninety one PTB patients were included, 7 of them developed hepatotoxicity. NAT2 SNPs (rs1801279, rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931) were genotyped by TaqMan allelic discrimination assay. Statistical analyses were performed using Epi Info statistical software 7.0 and SHEsisPlus for haplotype reconstruction. The NAT2 slow non-synonymous SNP were studied by molecular dynamic analysis (MDA). RESULTS: The frequency of the haplotype associated with slow acetylation status for PTB was 58%, and for with hepatotoxicity (PTB-H) represented 42.6%. Three haplotypes, NAT2*5Q, NAT2*5U, NAT2*5Va were exclusively present in seven PTB-H patients, (P = 0.01, P = 0.0006, P = 0.01, respectively). These haplotypes include the combination of two SNPs (I114T + R197Q or I114T + G286E). The effect of the SNPs on protein structure is to disrupt the CoA binding site affecting acetylation activity. CONCLUSION: Our study provides insight into slow acetylation NAT2 haplotypes associated with hepatotoxicity after first-line tuberculosis treatment, for first time, in a Mexican population. The molecular mechanism acts at the CoA binding site.

A new Terrarana frog of genus Pristimantis from an unexplored cloud forest from the eastern Andes, Colombia.

A new species of Pristimantis (Craugastoridae, subgenus Pristimantis) is described from a relict and unexplored cloud forest in the western slope from Cordillera Oriental of the Colombian Andes. The specific name was chosen by consensus expert scientists and local people. Pristimantis chamezensis sp. nov. is easily distinguished from congeneric species by having a gray iris with black reticulations in life, subconical tubercles on the upper eyelid, the chin edged with irregular, dark-brown blotches, and conical heel tubercles. The phylogenetic analyses suggest that the origin and radiation of its clade may have occurred in the highlands. With the description of P. chamezensis sp. nov., we identify 14 species distributed throughout the eastern slope of the Andes that are associated with the Orinoco Basin.

Association study of genetic polymorphisms in proteins involved in oseltamivir transport, metabolism, and interactions with adverse reactions in Mexican patients with acute respiratory diseases.

Oseltamivir, a pro-drug, is the best option for treatment and chemoprophylaxis for influenza outbreaks. However, many patients treated with oseltamivir developed adverse reactions, including hypersensitivity, gastritis, and neurological symptoms. The aim of this study was to determine the adverse drug reactions (ADRs) in Mexican patients treated with oseltamivir and whether these ADRs are associated with SNPs of the genes involved in the metabolism, transport, and interactions of oseltamivir. This study recruited 310 Mexican patients with acute respiratory diseases and treated them with oseltamivir (75 mg/day for 5 days) because they were suspected to have influenza A/H1N1 virus infection. Clinical data were obtained from medical records and interviews. Genotyping was performed using real-time polymerase chain reaction and TaqMan probes. The association was assessed under genetic models with contingency tables and logistic regression analysis. Out of 310 patients, only 38 (12.25%) presented ADRs to oseltamivir: hypersensitivity (1.9%), gastritis (10%), and depression and anxiety (0.9%). The polymorphism ABCB1-rs1045642 was associated with adverse drug reactions under the recessive model (P = 0.017); allele C was associated with no adverse drug reactions, while allele T was associated with adverse drug reactions. The polymorphisms SLC15A1-rs2297322, ABCB1-rs2032582, and CES1-rs2307243 were not consistent with Hardy-Weinberg equilibrium, and no other associations were found for the remaining polymorphisms. In conclusion, the polymorphism rs1045642 in the transporter encoded by the ABCB1 gene is a potential predictive biomarker of ADRs in oseltamivir treatment.

Association between vitamin D receptor gene polymorphisms and pulmonary tuberculosis in a Mexican population.

BACKGROUND AND AIMS: The impact of host genetic variation in susceptibility of tuberculosis is well documented. The vitamin D receptor gene (VDR) is a transacting transcription factor which mediates innate immune response by enhancing the expression of several antimicrobial peptides, including cathelicidin. An association between VDR polymorphisms with tuberculosis (TB) has been investigated in different ethnic groups; however there are contradictions and inconsistencies in the results. The aim of this study was to evaluate the association between polymorphisms of functional VDR with the susceptibility to pulmonary tuberculosis in a Mexican population. METHODS: A case-control study was performed in, 257 patients with pulmonary tuberculosis and 457 healthy controls recruited from: family medicine clinics of the Mexican Social Security Institute. The VDR gene polymorphisms Fok I (rs 2228570), BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) were genotyped by TaqMan assays. Statistical analysis was performed using: Epi Info V-7 and SNP Stats software. RESULTS: No statistically significant associations were observed in genotype and haplotype distribution between BsmI, ApaI and TaqI polymorphisms and disease susceptibility. The CC genotype for the VDR gene FokI was significantly more frequent in patients than in controls (29.6% versus 17.5%, OR=1.97; 95% CI=1.37-2.8, PC=0.0004). Moreover, TT genotype was decreased in patients as compared to the control group (24.1% versus 34.8%, OR=0.59; 95% CI=0.42-0.84, PC=0.004). CONCLUSION: To our best knowledge, this is the first case-control study that finds an association between CC genotype of FokI SNP in the VDR gene with pulmonary tuberculosis in Mexican patients. However more validation studies should be performed to prove our conclusions.

IL-1α and MMP-9 Tear Levels of Patients with Active Ocular Rosacea before and after Treatment with Systemic Azithromycin or Doxycycline.

AIMS: The purpose of this paper was to determine the lacrimal concentration of IL-1α and MMP-9 in patients with active ocular rosacea before and after systemic treatment with azithromycin or doxycycline. METHODS: After 4 weeks of therapy with azithromycin (500 mg/day, 3 days a week PO) or doxycycline (200 mg/day PO), lacrimal samples were analyzed using an enzyme-linked immunosorbent assay multiplex. RESULTS: There was a significant difference between baseline IL-1α (37.9 pg/mL) and MMP-9 (26.7 ng/mL) in rosacea eyes compared to controls (0.001 pg/mL for IL-1α and 0.2 ng/mL for MMP-9) (p < 0.001). IL-1α decreased from 47.0 pg/mL before azithromycin to 23.5 pg/mL after treatment (p = 0.024), but not after doxycycline therapy. On the contrary, baseline MMP-9 tear levels (10.28 ng/mL) decreased after treatment (8.36 pg/mL) with doxycycline (p = 0.054) but not with azithromycin. There was a strong clinical correlation of higher baseline IL-1α tear levels between patients who responded to doxycycline therapy and those who failed (p = 0.043). Patients unresponsive to azithromycin had significantly higher baseline MMP-9 levels than those with doxycycline (p = 0.040). CONCLUSIONS: While IL-1α levels decreased after azithromycin therapy, MMP-9 did so after doxycycline treatment. Baseline cytokine tear levels tend to be markedly elevated in patients with antibiotic failure, suggesting their potential role as therapeutic biomarkers for the disease.

Aerobic physical training does not condition against strenuous exercise-induced changes in immune function but modulates T cell proliferative responses.

BACKGROUND: Exercise-induced stress induces considerable changes in the immune system. To better understand the mechanisms related to these immune changes during acute and chronic physical stress, we studied the effects of aerobic physical training (APT) on several parameters of the immune system. METHODS: Previously untrained males (18-25 years of age) were divided into a group that was subjected to 6 months of APT (N.=10) and a sedentary control group (N.=7). The subjects performed a cardiopulmonary exercise test (CET) at 0, 3, and 6 months of the APT program. B cell (CD19+), T cell (CD4+ and CD8+), and natural killer cell (CD56+) levels, and mitogen-induced T cell proliferation and cytokine production (interleukin-1, interleukin-4, interleukin-12, and interferon-γ) were evaluated before and at 30 seconds and 24 hours after the CET. RESULTS: There was a significant increase in CD4+ T cells and natural killer cells and a significant reduction in T cell proliferation in both groups 30 seconds after the CET at 0, 3 and 6 months of the APT program. Of note, the trained group showed significantly lower resting T cell proliferation (before and 24 hour after the CET) than the sedentary control groups at 0, 3 and 6 months of the APT program. There were no significant differences in cytokine production after the CET between both groups at any time point of the APT program. CONCLUSIONS: These data show that APT does not condition against strenuous exercise-induced immune changes but significantly modulates T cell proliferative responses.

Caso relacionado con el proceso asistencial integrado cuidados paliativos en atención primaria de salud / Case related to the integrated palliative care process in primary health care level

La cirrosis hepática constituye una de las principales causas atribuibles a la mortalidad por consumo de alcohol. El caso que se presenta corresponde a un paciente de 58 años diagnosti-cado con dicha enfermedad terminal no oncológica e incluido en el Proceso Asistencial de Cuidados Paliativos, siguiendo una valoración según el modelo conceptual de Virginia Hen-derson y un plan de cuidados según la taxonomía North American Nursing Association, Nur-sing Intervention Classification, Nursing Outcomes Classification. De modo que, las inter-venciones y actividades se basaron principalmente en apoyar emocionalmente tanto al paciente como a la cuidadora principal. El plan de cuidados transita desde su identificación, hasta el cuidado del enfermo en los últimos días de la vida.

Liver cirrhosis is one of the main causes attributable to mortality due to alcohol consumption. The case presented corresponds to a 58-year-old patient diagnosed with this non-oncological terminal disease and included in the Palliative Care Process by following an assessment according to the Virginia Henderson conceptual model and a care plan according to the taxo-nomy North American Nursing Association, Nursing Intervention Classification, Nursing Outcomes Classification. Thus, the interventions and activities were mainly based on suppor-ting emotionally both the patient and the main caregiver. The care plan goes from its identifi-cation to the care of the patient in the last days of life.