Accumulation of Alpha-Synuclein and Increase in the Inflammatory Response in the substantia nigra, Jejunum, and Colon in a Model of O3 Pollution in Rats.

This work aimed to study the effect of repeated exposure to low doses of ozone on alpha-synuclein and the inflammatory response in the substantia nigra, jejunum, and colon. Seventy-two male Wistar rats were divided into six groups. Each group received one of the following treatments: The control group was exposed to air. The ozone groups were exposed for 7, 15, 30, 60, and 90 days for 0.25 ppm for four hours daily. Afterward, they were anesthetized, and their tissues were extracted and processed using Western blotting, immunohistochemistry, and qPCR. The results indicated a significant increase in alpha-synuclein in the substantia nigra and jejunum from 7 to 60 days of exposure and an increase in NFκB from 7 to 90 days in the substantia nigra, while in the jejunum, a significant increase was observed at 7 and 15 days and a decrease at 60 and 90 days for the colon. Interleukin IL-17 showed an increase at 90 days in the substantia nigra in the jejunum and increases at 30 days and in the colon at 15 and 90 days. Exposure to ozone increases the presence of alpha-synuclein and induces the loss of regulation of the inflammatory response, which contributes significantly to degenerative processes.

Changes in SOD and NF-κB Levels in Substantia Nigra and the Intestine through Oxidative Stress Effects in a Wistar Rat Model of Ozone Pollution.

This work aimed to elucidate how O3 pollution causes a loss of regulation in the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 based on the association between the antioxidant response of superoxide dismutase (SOD) levels and the nuclear factor kappa light chains of activated B cells (NFκB) as markers of inflammation. Method: Seventy-two Wistar rats were used, divided into six groups that received the following treatments: Control and 7, 15, 30, 60, and 90 days of O3. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD and a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decreased. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to O3 alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This indicates that these factors are critical in the loss of regulation in the inflammatory response; they respond to ozone pollution, which can occur in chronic degenerative diseases.

Chronic hyperkalemia, diagnosis and management. Colombian consensus.

OBJECTIVE: Generate recommendations for the diagnosis, management, and follow-up of chronic hyperkalemia. METHOD: This consensus was made by nephrologists and cardiologists following the GRADE methodology. RESULTS: Chronic hyperkalemia can be defined as a biochemical condition with or without clinical manifestations characterized by a recurrent elevation of serum potassium levels that may require pharmacological and or non-pharmacological intervention. It can be classified as mild (K+ 5.0 to < 5.5 mEq/L), moderate (K+ 5.5 to 6.0 mEq/L) or severe (K+ > 6.0 mEq/L). Its incidence and prevalence have yet to be determined. Risk factors: chronic kidney disease, chronic heart failure, diabetes mellitus, age ≥ 65 years, hypertension, and drugs that inhibit the renin angiotensin aldosterone system (RAASi), among others. There is no consensus for the management of chronic hyperkalemia. The suggested pattern for patients is to identify and eliminate or control risk factors, provide advice on potassium intake and, for whom it is indicated, optimize RAASi therapy, administer oral potassium binders and correct metabolic acidosis. CONCLUSIONS: The recommendation is to pay attention to the diagnosis, management, and follow-up of chronic hyperkalemia, especially in patients with risk factors.

OBJETIVO: Generar recomendaciones para el diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica. MÉTODO: Este consenso fue realizado por nefrólogos y cardiólogos siguiendo la metodología GRADE. RESULTADOS: La hiperkalemia crónica puede definirse como una condición bioquímica, con o sin manifestaciones clínicas, caracterizada por una elevación recurrente de las concentraciones séricas de potasio que puede requerir una intervención farmacológica, no farmacológica o ambas. Puede clasificarse en leve (K+ 5,0 a < 5,5 mEq/l), moderada (K+ 5,5 a 6,0 mEq/l) o grave (K+ > 6,0 mEq/l). Su incidencia y prevalencia no han sido claramente determinadas. Se consideran factores de riesgo la enfermedad renal crónica, la insuficiencia cardiaca crónica, la diabetes mellitus, la edad ≥ 65 años, la hipertensión arterial y el tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA), entre otros. No hay consenso sobre el manejo de la hiperkalemia crónica. Se sugiere identificar y eliminar o controlar los factores de riesgo, brindar asesoramiento sobre la ingesta de potasio y, para quien esté indicado, optimizar la terapia con iSRAA, administrar aglutinantes orales del potasio y corregir la acidosis metabólica. CONCLUSIONES: Se recomienda prestar atención al diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica, en especial en los pacientes con factores de riesgo.

Ozone Environmental Pollution: Relationship between the Intestine and Neurodegenerative Diseases.

Repeated exposure to environmental ozone causes a chronic state of oxidative stress. This state is present in chronic degenerative diseases and induces a loss of control of the inflammatory response. Redox system dysfunction and failures in control of inflammatory responses are involved in a vicious circle that maintains and increases the degenerative process. The intestine also responds to secondary reactive species formed by exposure to ozone doses, generating noxious stimuli that increase degenerative damage. This review aims to elucidate how environmental pollution, mainly by ozone, induces a state of chronic oxidative stress with the loss of regulation of the inflammatory response, both in the intestine and in the brain, where the functionality of both structures is altered and plays a determining role in some neurodegenerative and chronic degenerative diseases. For this purpose, we searched for information on sites such as the Cochrane Library Database, PubMed, Scopus, and Medscape. Reviewing the data published, we can conclude that environmental pollutants are a severe health problem. Ozone pollution has different pathways of action, both molecular and systemic, and participates in neurodegenerative diseases such as Parkinson's and Alzheimer's disease as well in bowel diseases as Inflammatory Bowel Disease, Crohn's Disease, and Irritable Bowel Syndrome.

Effect of the Addition of Different Natural Waxes on the Mechanical and Rheological Behavior of PLA-A Comparative Study.

In this study, poly(lactic acid) (PLA) blended with different natural waxes (beeswax, candelilla, carnauba, and cocoa) was investigated. Different wax amounts, 3, 5, 10, and 15 wt%, were incorporated into the PLA using a Brabender internal mixer. The blends were characterized by thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), rotational rheometer (RR), dynamic mechanical analysis (DMA), and contact angle to observe the effect of the different waxes on the PLA physicochemical, rheological, mechanical behavior, and wetting properties. The complex viscosity of the blends was studied by employing a RR. The effect of the addition of the waxes on the mechanical properties of PLA was evaluated by DMA in the tension modality. A slight decrease in the thermal stability of PLA was observed with the addition of the waxes. However, in the case of the mechanical properties, the cocoa wax showed a considerable effect, especially in the elongation at break of PLA. Likewise, waxes had an essential impact on the water affinity of PLA. Specifically, with the addition of cocoa, the PLA became more hydrophilic, while the rest of the waxes increased the hydrophobic character.

Hiperkalemia crónica, diagnóstico y manejo. Consenso colombiano / Chronic hyperkalemia, diagnosis and management. Colombian consensus

Resumen Objetivo: Generar recomendaciones para el diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica. Método: Este consenso fue realizado por nefrólogos y cardiólogos siguiendo la metodología GRADE. Resultados: La hiperkalemia crónica puede definirse como una condición bioquímica, con o sin manifestaciones clínicas, caracterizada por una elevación recurrente de las concentraciones séricas de potasio que puede requerir una intervención farmacológica, no farmacológica o ambas. Puede clasificarse en leve (K+ 5,0 a < 5,5 mEq/l), moderada (K+ 5,5 a 6,0 mEq/l) o grave (K+ > 6,0 mEq/l). Su incidencia y prevalencia no han sido claramente determinadas. Se consideran factores de riesgo la enfermedad renal crónica, la insuficiencia cardiaca crónica, la diabetes mellitus, la edad ≥ 65 años, la hipertensión arterial y el tratamiento con inhibidores del sistema renina-angiotensina-aldosterona (iSRAA), entre otros. No hay consenso sobre el manejo de la hiperkalemia crónica. Se sugiere identificar y eliminar o controlar los factores de riesgo, brindar asesoramiento sobre la ingesta de potasio y, para quien esté indicado, optimizar la terapia con iSRAA, administrar aglutinantes orales del potasio y corregir la acidosis metabólica. Conclusiones: Se recomienda prestar atención al diagnóstico, el manejo y el seguimiento de la hiperkalemia crónica, en especial en los pacientes con factores de riesgo.

Abstract Objective: Generate recommendations for the diagnosis, management, and follow-up of chronic hyperkalemia. Method: This consensus was made by nephrologists and cardiologists following the GRADE methodology. Results: Chronic hyperkalemia can be defined as a biochemical condition with or without clinical manifestations characterized by a recurrent elevation of serum potassium levels that may require pharmacological and or non-pharmacological intervention. It can be classified as mild (K+ 5.0 to < 5.5 mEq/L), moderate (K+ 5.5 to 6.0 mEq/L) or severe (K+ > 6.0 mEq/L). Its incidence and prevalence have yet to be determined. Risk factors: chronic kidney disease, chronic heart failure, diabetes mellitus, age ≥ 65 years, hypertension, and drugs that inhibit the renin angiotensin aldosterone system (RAASi), among others. There is no consensus for the management of chronic hyperkalemia. The suggested pattern for patients is to identify and eliminate or control risk factors, provide advice on potassium intake and, for whom it is indicated, optimize RAASi therapy, administer oral potassium binders and correct metabolic acidosis. Conclusions: The recommendation is to pay attention to the diagnosis, management, and follow-up of chronic hyperkalemia, especially in patients with risk factors.

Characteristics and Outcomes of Heart Failure Patients from a Middle-Income Country: The RECOLFACA Registry.

Background: There is a lack of epidemiological data around heart failure (HF) in Latin America; the potential impact description of this disease in middle-income countries is relevant. Objective: This study aimed to describe the characteristics and healthcare resource utilization patterns of HF patients at baseline and six-month follow-up. Methods: This retrospective observational study used data from the RECOLFACA (Registro Colombiano de Falla Cardíaca) registry, which includes data obtained from the examination of clinical records from 2,528 patients in 60 Colombian healthcare institutions. Baseline and six-month follow-up data were evaluated from patients with previous hospital admissions due to HF during the 12 months prior to enrollment. Results: This study analyzed 2,045 patients (42.8% female) with a mean age of 67.71 ± 13.64 years. The most common etiologies were ischemic (44.4%) and hypertensive heart disease (38.5%). At baseline, 53.4% of patients were classified with NYHA class II, and 73.6% had a reduced left ventricle ejection fraction (LVEF). A year prior to entering the registry, patients were hospitalized an average of 1.4 ± 1.1 times due to HF. Prescription of evidence-based treatment at baseline included sacubitril/valsartan (10%), ACEI (33%), ARB (41%), beta-blocker (79%), diuretics (68%), and MRA (56%). The average quality of life score measured using the EQ-5D-3L questionnaire was 78.7 ± 20.8 at baseline and 82.3 ± 20.1 at the six-month follow-up. The mortality rate was 6.7%. Conclusions: The use of information from the RECOLFACA registry allowed characterization as well as analyses of healthcare resource utilization of patients with heart failure in Colombia. The results of this study show that multiple evidence-based treatments for HF are being widely used in Colombia, but there seems to be room for improvement regarding some interventions for the treatment of patients with HF.

Ozone Pollution, Oxidative Stress, Regulatory T Cells and Antioxidants.

Ozone pollution, is a serious health problem worldwide. Repeated exposure to low ozone doses causes a loss of regulation of the oxidation-reduction systems, and also induces a chronic state of oxidative stress. This fact is of special importance for the regulation of different systems including the immune system and the inflammatory response. In addition, the oxidation-reduction balance modulates the homeostasis of these and other complex systems such as metabolism, survival capacity, cell renewal, and brain repair, etc. Likewise, it has been widely demonstrated that in chronic degenerative diseases, an alteration in the oxide-reduction balance is present, and this alteration causes a chronic loss in the regulation of the immune response and the inflammatory process. This is because reactive oxygen species disrupt different signaling pathways. Such pathways are related to the role of regulatory T cells (Treg) in inflammation. This causes an increase in chronic deterioration in the degenerative disease over time. The objective of this review was to study the relationship between environmental ozone pollution, the chronic state of oxidative stress and its effect on Treg cells, which causes the loss of regulation in the inflammatory response as well as the role played by antioxidant systems in various pathologies.

Oxidative Stress Caused by Ozone Exposure Induces Changes in P2X7 Receptors, Neuroinflammation, and Neurodegeneration in the Rat Hippocampus.

Low-ozone doses cause alterations in the oxidation-reduction mechanisms due to the increase in reactive oxygen species, alter cell signaling, and produce deleterious metabolic responses for cells. Adenosine 5'triphosphate (ATP) can act as a mediator in intercellular communication between neurons and glial cells. When there is an increase in extracellular ATP, a modification is promoted in the regulation of inflammation, energy metabolism, by affecting the intracellular signaling pathways that participate in these processes. The objective of this work was to study changes in the P2X7 receptor, and their relationship with the inflammatory response and energy metabolism, in a model of progressive neurodegeneration in the hippocampus of rats chronically exposed to low-ozone doses. Therefore, 72 male rats were exposed to low-ozone doses for different periods of time. After exposure to ozone was finished, rats were processed for immunohistochemical techniques, western blot, quantitative polymerase chain reaction (qPCR), and histological techniques for periodic acid-Schiff staining. The results showed immunoreactivity changes in the amount of the P2X7 protein. There was an increase in phosphorylation for glycogen synthase kinase 3-ß (GSK3-ß) as treatment continued. There were also increases in 27 interleukin 1 beta (IL-1 ß) and interleukin 17 (IL-17) and a decrease in interleukin 10 (IL-10). Furthermore, neuronal glycogen was found at 30 and 60 days, and an increase in caspase 3. An increase in mRNA was also shown for the P2X7 gene at 60 days, and GSK3-ß at 90 days of exposure. In conclusion, these results suggest that repeated exposure to low-ozone doses, such as those that can occur during highly polluted days, causes a state of oxidative stress, leading to alterations in the P2X7 receptors, which promote changes in the activation of signaling pathways for inflammatory processes and cell death, converging at a progressive neurodegeneration process, as may be happening in Alzheimer's disease.

Principales recomendaciones de reanimación cardiopulmonar y atención cardiovascular de emergencia para el año 2020 / Best practice recommendations for cardiopulmonary resuscitation and emergency cardiovascular care for 2020

Las altas tasas de letalidad y mortalidad a causa del paro cardiorespiratorio por fibrilación ventricular son considerados un problema de salud pública, cobrando gran relevancia la posibilidad de que sean revertidos rápidamente con la presencia de profesionales capacitados o por personal "lego" actualizados en reanimación cardiopulmonar. El objetivo del presente artículo de revisión fue analizar las nuevas recomendaciones de la American Heart Association para reanimación cardiopulmonar y atención cardiovascular de emergencia para el año 2020.

High rates of lethality and mortality due to ventricular fibrillation cardiorespiratory arrest are considered a public health problem, Thus, the possibility of reversed quickly by trained professionals or updated "lego" staff in cardiopulmonary resuscitation is taking great relevance. The objective of this review article was to discuss the New Recommendations of the American Heart Association for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care for 2020.

Curing of Cellulose Hydrogels by UV Radiation for Mechanical Reinforcement.

The use of biomaterials as a replacement for thermoplastic polymers is an environmentally sound strategy. In this work, hydrogels of cellulose isolated from wheat husk were modified by UV irradiation (353 nm) to improve mechanical performance. The cellulose was dissolved with a solvent system N,N-dimethylacetamide/lithium chloride (DMAc/LiCl). Infrared spectroscopy showed that the peak height at 1016 cm-1, associated with the C-O bonds of the glycosidic ring, increases with irradiation time. It was determined that the increase in this signal is related to photodegradation, the product of a progressive increase in exposure to UV radiation. The viscoelastic behavior, determined by dynamic mechanical analysis and rotational rheometry, was taken as the most important parameter of this research, showing that the best results are recorded with 15 min of UV treatment. Therefore, at this time or less, the chemical crosslinking is predominant over the photodegradation, producing an increase in the modules, while with 20 min the photodegradation is such that the modules suffer a significant reduction.

Epidemiología del cáncer de estómago en un centro de referencia del Ecuador / Epidemiology of gastric cancer in a referral center in Ecuador

El cáncer gástrico es el tumor maligno más frecuente del Ecuador. A pesar de los avances en los métodos de diagnóstico y de las terapias oncológicas, la mayoría de los casos se diagnostican en etapas avanzadas de la enfermedad con pobre pronóstico y alta mortalidad. El objetivo de este estudio fue determinar las características epidemiológicas en pacientes atendidos con cáncer gástrico en un centro de referencia del Ecuador. Pacientes y métodos Fue un estudio retrospectivo transversal, fueron elegibles para participar del estudio pacientes atendidos en el Servicio de Oncología del Hospital de Especialidades Eugenio Espejo (HEEE) entre marzo del 2012 y marzo del 2017. Los datos epidemiológicos, clínicos y relacionados con el CG, se recopilaron de las historias clínicas. Resultados Durante el período de estudio se evaluaron 159 pacientes, la mediana de edad fue 61 años y el 52,80 % fueron del sexo masculino. El síntoma más frecuente al diagnóstico fue el dolor abdominal en 59% de los casos. El estadio de la enfermedad en 72% de los pacientes fue loco regionalmente avanzado y diseminado. Aquellos pacientes que se sometieron a cirugía; presentaron mayor sobrevida. Conclusión El 50% de los casos fueron diagnosticados en etapas avanzadas de la enfermedad y se asociaron a pobre pronóstico y alta mortalidad. Las características clínicas y epidemiológicas de este primer estudio realizado en el HEEE permitirán establecer medidas que permitan mejorar el screening y diagnóstico precoz de los pacientes.

Gastric cancer is the most common malignant tumor in Ecuador. Despite advances in diagnostic methods and cancer therapies, most cases are diagnosed in advanced stages of the disease with poor prognosis and high mortality. The objective of this study was to determine epidemiological characteristics in patients treated with gastric cancer at a reference center in Ecuador. Patients and methods It was a cross-sectional retrospective study, patients were eligible in the Oncology Service of the Hospital de Especialidades Eugenio Espejo (HEEE) between March 2012 and March 2017. data were collected from medical records. Results during the study period 159 patients were evaluated, the median age was 61 years and 52.80% were male. The most common symptom of diagnosis was abdominal pain in 59% of cases. The stage of the disease in 72% of patients was regionally advanced and widespread. Those patients who underwent surgery; presented more survival. Conclusions 50% of cases were diagnosed in advanced stages of the disease and were associated with poor prognosis and high mortality. The clinical and epidemiological characteristics of this first study carried out in the HEEE, will allow to establish measures to improve the screening and early diagnosis of patients.

Detección y genotipificación de Pneumocystis jirovecii en muestras de pacientes mexicanos VIH positivos y negativos.

INTRODUCTION: Pneumocystis jirovecii is an atypical fungus particularly detected in HIV-positive or transplant patients. OBJECTIVE: To detect and genotype Pneumocystis jirovecii in patient samples from two hospitals in Mexico City. METHOD: Eighty-nine respiratory tract samples, corresponding to 53 patients (30 HIV-positive and 23 HIV-negative) with respiratory symptoms and to 11 healthy individuals included as negative control, were processed. DNA was extracted from the ITS region and amplified by nested polymerase chain reaction from the internal transcribed spacer, with one fragment being obtained at each round (693 and 550 bp). Genotypes and their phylogenetic relationship were determined by sequencing the 550 bp fragment. RESULTS: Forty-eight samples from 30 HIV-positive patients were received from a single hospital, out of which 11 (36.6 %) were positive for Pneumocystis jirovecii. No sample was positive in HIV-negative patients or healthy subjects. The most frequently detected haplotypes were Eg and Em. CONCLUSIONS: The frequency of Pneumocystis jirovecii infection was high in the studied Mexican population. The most common genotype was different from those reported in other countries. It is necessary to address this health problem through early detection of this infection.

INTRODUCCIÓN: Pneumocystis jirovecii es un hongo atípico detectado particularmente en pacientes VIH-positivos o con trasplante. OBJETIVO: Detectar y genotipificar Pneumocystis jirovecii en muestras de pacientes de dos hospitales de la ciudad de México. MÉTODO: Fueron procesadas 89 muestras respiratorias, correspondientes a 53 pacientes (30 VIH positivos y 23 VIH negativos) con sintomatología respiratoria y 11 personas sanas incluidas como control negativo. El DNA fue extraído y amplificado por PCR anidada de la región del espaciador transcrito interno, obteniendo un fragmento en cada ronda (de 693 y 550 pb). Los genotipos y su relación filogenética fueron determinados por secuenciación del fragmento de 550 pb. RESULTADOS: Cuarenta y ocho muestras de 30 pacientes VIH-positivos provenían de un solo hospital, de las cuales 11 (36.6 %) fueron positivas a Pneumocystis jirovecii. Ninguna fue positiva en pacientes VIH-negativos o personas sanas. Los haplotipos detectados con mayor frecuencia fueron Eg y Em. CONCLUSIONES: La frecuencia de infección por Pneumocystis jirovecii fue alta en la población mexicana estudiada. El genotipo más frecuente fue diferente a los reportados en otros países. Es necesario encauzar este problema de salud hacia la detección temprana de esta infección.

Detección y genotipificación de Pneumocystis jirovecii en muestras de pacientes mexicanos VIH positivos y negativos / Detection and genotyping of Pneumocystis jirovecii in samples from HIV positive and negative Mexican patients

Resumen Introducción: Pneumocystis jirovecii es un hongo atípico detectado particularmente en pacientes VIH-positivos o con trasplante. Objetivo: Detectar y genotipificar Pneumocystis jirovecii en muestras de pacientes de dos hospitales de la ciudad de México. Método: Fueron procesadas 89 muestras respiratorias, correspondientes a 53 pacientes (30 VIH positivos y 23 VIH negativos) con sintomatología respiratoria y 11 personas sanas incluidas como control negativo. El DNA fue extraído y amplificado por PCR anidada de la región del espaciador transcrito interno, obteniendo un fragmento en cada ronda (de 693 y 550 pb). Los genotipos y su relación filogenética fueron determinados por secuenciación del fragmento de 550 pb. Resultados: Cuarenta y ocho muestras de 30 pacientes VIH-positivos provenían de un solo hospital, de las cuales 11 (36.6 %) fueron positivas a Pneumocystis jirovecii. Ninguna fue positiva en pacientes VIH-negativos o personas sanas. Los haplotipos detectados con mayor frecuencia fueron Eg y Em. Conclusiones: La frecuencia de infección por Pneumocystis jirovecii fue alta en la población mexicana estudiada. El genotipo más frecuente fue diferente a los reportados en otros países. Es necesario encauzar este problema de salud hacia la detección temprana de esta infección.

Abstract Introduction: Pneumocystis jirovecii is an atypical fungus particularly detected in HIV-positive or transplant patients. Objective: To detect and genotype Pneumocystis jirovecii in patient samples from two hospitals in Mexico City. Method: Eighty-nine respiratory tract samples, corresponding to 53 patients (30 HIV-positive and 23 HIV-negative) with respiratory symptoms and to 11 healthy individuals included as negative control, were processed. DNA was extracted from the ITS region and amplified by nested polymerase chain reaction from the internal transcribed spacer, with one fragment being obtained at each round (693 and 550 bp). Genotypes and their phylogenetic relationship were determined by sequencing the 550 bp fragment. Results: Forty-eight samples from 30 HIV-positive patients were received from a single hospital, out of which 11 (36.6 %) were positive for Pneumocystis jirovecii. No sample was positive in HIV-negative patients or healthy subjects. The most frequently detected haplotypes were Eg and Em. Conclusions: The frequency of Pneumocystis jirovecii infection was high in the studied Mexican population. The most common genotype was different from those reported in other countries. It is necessary to address this health problem through early detection of this infection.

Drug Levels and Antibodies Against TNF-blockers in Spondyloarthritis and Rheumatoid Arthritis are Associated with the Activity but they do Not Predict it.

BACKGROUND: Many patients may have resistance to TNF-blockers. These drugs may induce neutralizing antibodies. The determination of the drug levels of TNF-blockers and Anti-Drug Antibodies (ADAs) against TNF-blockers may help to make clinical decisions. OBJECTIVES: The objective of this study was to associate and predict the drug levels of TNFblockers and ADAs in relation to disease activity in patients with Spondyloarthritis (SpA) and Rheumatoid Arthritis (RA). METHODS: Cross-sectional study including patients fulfilling ASAS classification criteria for SpA and 2010 ACR-EULAR classification criteria for RA. These patients were treated with Adalimumab (ADA), Infliximab (IFX), and Etanercept (ETN). A bivariate analysis and the chi-square test were performed to evaluate the association of ADAs and drug levels with activity measures for SpA and RA. Five regression models analyzing drug levels, ADAs and disease activity measures using a multiple linear regression were performed in order to evaluate the prediction of ADAs and drug levels in relation to disease activity. RESULTS: In SpA, IFX levels were associated with BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) (p=0.034). In RA, total drug levels were associated with DAS28-ESR (28 joint Disease activity Score-erythrocyte sedimentation rate), (p=0.008), DAS28-CRP (p=0.042), CDAI (Clinical Disease Activity Index) (p=0.047) and SDAI (Simple Disease activity index), (p=0.017). ADA levels had association with CDAI (p=0.002) and SDAI (p=0.002). IFX levels were associated with a DAS28-ESR (p=0.044), DAS28-CRP (p=0.022) and SDAI (p=0.022). ADAs were associated in SpA with BASDAI (p=0.027). Drug levels and ADAs did not predict disease activity in patients with SpA or RA. CONCLUSION: ADAs and drug levels of anti-TNF are associated with disease activity measures in patients with SpA and RA. However, they cannot predict clinical activity in these conditions.

From Elemental Sulfur to Hydrogen Sulfide in Agricultural Soils and Plants.

Sulfur is an essential element in determining the productivity and quality of agricultural products. It is also an element associated with tolerance to biotic and abiotic stress in plants. In agricultural practice, sulfur has broad use in the form of sulfate fertilizers and, to a lesser extent, as sulfite biostimulants. When used in the form of bulk elemental sulfur, or micro- or nano-sulfur, applied both to the soil and to the canopy, the element undergoes a series of changes in its oxidation state, produced by various intermediaries that apparently act as biostimulants and promoters of stress tolerance. The final result is sulfate S+6, which is the source of sulfur that all soil organisms assimilate and that plants absorb by their root cells. The changes in the oxidation states of sulfur S0 to S+6 depend on the action of specific groups of edaphic bacteria. In plant cells, S+6 sulfate is reduced to S-2 and incorporated into biological molecules. S-2 is also absorbed by stomata from H2S, COS, and other atmospheric sources. S-2 is the precursor of inorganic polysulfides, organic polysulfanes, and H2S, the action of which has been described in cell signaling and biostimulation in plants. S-2 is also the basis of essential biological molecules in signaling, metabolism, and stress tolerance, such as reactive sulfur species (RSS), SAM, glutathione, and phytochelatins. The present review describes the dynamics of sulfur in soil and plants, considering elemental sulfur as the starting point, and, as a final point, the sulfur accumulated as S-2 in biological structures. The factors that modify the behavior of the different components of the sulfur cycle in the soil-plant-atmosphere system, and how these influences the productivity, quality, and stress tolerance of crops, are described. The internal and external factors that influence the cellular production of S-2 and polysulfides vs. other S species are also described. The impact of elemental sulfur is compared with that of sulfates, in the context of proper soil management. The conclusion is that the use of elemental sulfur is recommended over that of sulfates, since it is beneficial for the soil microbiome, for productivity and nutritional quality of crops, and also allows the increased tolerance of plants to environmental stresses.

First report of infectious endocarditis due to Histoplasma capsulatum in Mexico / Primer reporte de endocarditis infecciosa por Histoplasma capsulatum en México

Background: Infectious endocarditis of fungal origin is rare but of high mortality. The agents involved are mainly opportunists of the genus Candida and Aspergillus; however other fungi can also cause this disease. Clinical case: The case of a woman who suffered unknown origin intermittent fever for several months; and in who, by blood culture (after lysis-centrifugation) and molecular biology techniques, Histoplasma capsulatum was identified as etiological agent. The histological study showed abundant intracellular yeasts and hyphae in intracardiac vegetations. Conclusion: This first report of infectious endocarditis by H. capsulatum in Mexico highlights the importance of using in addition to manual blood culture (lysis-centrifugation) and histological study, faster and more sensitive diagnostic methods, such as serology and molecular biology, to confirm or rule out an invasive fungal infection and identify the agents.

Introducción: la endocarditis infecciosa de etiología micótica es una patología poco frecuente, pero con elevada mortalidad. Los agentes implicados generalmente son oportunistas de los géneros Candida y Aspergillus; sin embargo, otros hongos también pueden ocasionar la enfermedad. Caso clínico: se presenta el caso de una mujer quien cursó con fiebre intermitente de causa desconocida por varios meses y en la que, por medio de estudios de imagen, hemocultivo manual (después de lisis-centrifugación) y técnicas de biología molecular, se identificó Histoplasma capsulatum. El estudio histológico de las vegetaciones intracardiacas mostró abundantes levaduras e hifas. Conclusión: este primer reporte de endocarditis infecciosa por H. capsulatum en México pone en evidencia la importancia de utilizar, además del hemocultivo manual (lisis-centrifugación) y el estudio histológico, métodos de diagnóstico más rápidos y sensibles, como la serología y la biología molecular, para confirmar o descartar una infección fúngica invasiva e identificar los agentes.

Etiological identification of viral agents in acute encephalitis in Guadalajara, México, 2011-2015

Introduction: Viral encephalitis is a well-known inflammatory process associated with neurological dysfunction that might derive into severe brain damage or a fatal outcome. In México there is no epidemiological data that describes the prevalence of viral agents responsible for acute encephalitis. Objective: To identify the main viral agents by real time PCR involved in acute encephalitis in Mexico. Materials and methods: We obtained cerebral spinal fluid (CSF) samples from all patients with suspected viral encephalitis admitted to the emergency service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde". To identify pathogens, we performed nucleic acid extraction using real-time PCR and RT-PCR. Results: Sixty-six patients were diagnosed with acute encephalitis from 2011 to 2014. A definitive viral etiological diagnosis was established in 16 patients (24%); the main causative agents were enteroviruses in 50% of the 16 positive samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%). Patients with encephalitis were predominantly male (63.3%) and a seasonal predominance was observed during autumn (37.5%). The main clinical characteristics in the acute encephalitis phase were fever (48.45) and cephalea (36.3), followed by seizures, disorientation, and muscular weakness (30.3%). Kerning sign was present in two cases (3%) and other two cases presented Brudzinski's sign (3%). Conclusions: CSF PCR is a suitable diagnostic technique for the identification of viral encephalitis caused by viral infections that allows an appropriate antiviral therapeutic treatment.

Identificación etiológica de agentes virales de la encefalitis aguda en Guadalajara, México, 2011-2015 / Etiological identification of viral agents in acute encephalitis in Guadalajara, México, 2011-2015

Resumen Introducción. La encefalitis viral aguda se define como un proceso inflamatorio asociado a disfunción neurológica con desenlace fatal o daño grave permanente. En México no se han hecho estudios de identificación directa de los agentes etiológicos causales de la encefalitis viral aguda. Objetivo. Identificar mediante PCR en tiempo real los principales agentes virales causantes de encefalitis viral aguda en México. Materiales y métodos. Se obtuvo el líquido cefalorraquídeo de pacientes con sospecha de encefalitis viral que ingresaron al servicio de urgencias del Hospital Civil Fray Antonio Alcalde. Se extrajeron ácidos nucleicos para identificar los patógenos mediante PCR y PCR con transcripción inversa en tiempo real. Resultados. Se captaron un total de 66 pacientes entre el 2011 y el 2014. En 16 de los casos (24 %) se identificó el agente viral y se encontró que el principal agente causal fue el enterovirus, con ocho casos (50 %), seguido del virus del herpes simple (HSV: 37 %), con seis casos, y el citomegalovirus (CMV: 12,5 %), con dos casos. El promedio de edad fue de 25 años (0-70 años). Los casos positivos predominaron en los varones (63,3 %) y se estableció un predominio estacional en otoño (37,5 %). La mayoría de los pacientes presentó fiebre (48,4 %) o cefalea (36,3 %) y, en menor proporción, convulsiones, confusión y debilidad muscular (30,3 %) seguidas de desorientación (28,75 %) y apatía (25,7 %). En dos de los casos se observó el signo de Kerning (3 %) y en otros dos, el signo de Brudzinski (3 %). Conclusiones. La PCR en líquido cefalorraquídeo es una técnica de diagnóstico adecuada para la identificación de virus causales de encefalitis viral, lo cual permite prescribir los medicamentos específicos.

Abstract Introduction: Viral encephalitis is a well-known inflammatory process associated with neurological dysfunction that might derive into severe brain damage or a fatal outcome. In México there is no epidemiological data that describes the prevalence of viral agents responsible for acute encephalitis. Objective: To identify the main viral agents by real time PCR involved in acute encephalitis in Mexico. Materials and methods: We obtained cerebral spinal fluid (CSF) samples from all patients with suspected viral encephalitis admitted to the emergency service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde". To identify pathogens, we performed nucleic acid extraction using real-time PCR and RT-PCR. Results: Sixty-six patients were diagnosed with acute encephalitis from 2011 to 2014. A definitive viral etiological diagnosis was established in 16 patients (24%); the main causative agents were enteroviruses in 50% of the 16 positive samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%). Patients with encephalitis were predominantly male (63.3%) and a seasonal predominance was observed during autumn (37.5%). The main clinical characteristics in the acute encephalitis phase were fever (48.45) and cephalea (36.3), followed by seizures, disorientation, and muscular weakness (30.3%). Kerning sign was present in two cases (3%) and other two cases presented Brudzinski's sign (3%). Conclusions: CSF PCR is a suitable diagnostic technique for the identification of viral encephalitis caused by viral infections that allows an appropriate antiviral therapeutic treatment.

Structural Changes of Amyloid Beta in Hippocampus of Rats Exposed to Ozone: A Raman Spectroscopy Study.

The aim of this work was to study the effect of oxidative stress on the structural changes of the secondary peptide structure of amyloid beta 1-42 (Aß 1-42), in the dentate gyrus of hippocampus of rats exposed to low doses of ozone. The animals were exposed to ozone-free air (control group) and 0.25 ppm ozone during 7, 15, 30, 60, and 90 days, respectively. The samples were studied by: (1) Raman spectroscopy to detect the global conformational changes in peptides with α-helix and ß-sheet secondary structure, following the deconvolution profile of the amide I band; and (2) immunohistochemistry against Aß 1-42. The results of the deconvolutions of the amide I band indicate that, ozone exposure causes a progressively decrease in the abundance percentage of α-helix secondary structure. Furthermore, the ß-sheet secondary structure increases its abundance percentage. After 60 days of ozone exposure, the ß-sheet band is identified in a similar wavenumber of the Aß 1-42 peptide standard. Immunohistochemistry assays show an increase of Aß 1-42 immunoreactivity, coinciding with the conformational changes observed in the Raman spectroscopy of Aß 1-42 at 60 and 90 days. In conclusion, oxidative stress produces changes in the folding process of amyloid beta peptide structure in the dentate gyrus, leading to its conformational change in a final ß-sheet structure. This is associated to an increase in Aß 1-42 expression, similar to the one that happens in the brain of Alzheimer's Disease (AD) patients.