Guía de actuación y abordaje frente a intoxicación por dióxido de cloro/clorito de sodio, a partir de la experiencia de los CIAT de América Latina / Guidelines for action and approach to chlorine dioxide/sodium chlorite poisoning based on the experience of the CIATs in Latin America

Resumen El 11 de marzo de 2020, la Organización Mundial de la Salud, declaró la pandemia a nivel mundial por la COVID-19. Ante este escenario, los centros de información y asesoramiento toxicológico (CIAT) de América Latina comenzaron a recibir consultas por exposición/intoxicación a dióxido de cloro/clorito de sodio y sus compuestos relacionados, por desvío de uso, destinado a la prevención y/o tratamiento de la COVID-19 sin aval científico alguno ni contar con registro sanitario para ese fin. A través de la Red de Toxicología de América Latina y el Caribe (RETOXLAC), se comprobó que no eran hechos aislados, sino que se estaba produ ciendo el mismo fenómeno en toda la región y que existían antecedentes de intoxicaciones con dichos productos y alertas desde hace más de una década, con indicaciones no aprobadas, para el tratamiento de distintas patologías como SIDA, cáncer, esclerosis lateral amiotrófica ELA, malaria, autismo, entre otras, sin evidencia. Ante esta realidad, los CIAT presentan una revisión de los signos y síntomas observados según la vía de ingreso, basados en la comunicación de riesgo en salud; proponiéndose pruebas de apoyo al diagnóstico, algoritmo de tratamiento para las intoxicaciones y modelo de ficha clínica para la vigilancia epidemiológica de los casos atendidos. Recomendamos a las autoridades y organismos responsables, reforzar las acciones tendientes a la vigilancia, control y prevención de este tipo de intoxicaciones, producto del mal uso de un desinfectante no autorizado para fines terapéuticos/médicos.

Abstract On March 11th, 2020, the World Health Organization declared a global pandemic due to COVID-19. Faced with this sce- nario, the Poison Control Centers (CIATs for its initials in spanish) in Latin America began to receive consultations for exposure/poi- soning to chlorine dioxide/sodium chlorite and its related compounds for their use aimed to prevent or treat COVID-19 without any scientific endorsement or having a sanitary registry for that purpose. It was found through the Toxicology Network of Latin America and the Caribbean (RETOXLAC) that they were not isolated events but rather that the same phenomenon was occurring throughout the region and that there has been a history of poisoning and alerts with these products for more than a decade with unapproved indications for the treatment of different pathologies such as AIDS, cancer, amyotrophic lateral sclerosis (ALS), malaria, autism, among others, without evidence. In the light of this situation, the CIATs present a review of the signs and symptoms observed ac- cording to the route of exposure based on health risk communication; proposing tests to support the diagnosis, an algorithm for poisoning treatment, and a model of a clinical record for the epidemiological surveillance of the assisted cases. We recommend to the authorities and responsible organisms reinforce the actions aimed at surveillance, control, and prevention of this type of poisoning due to the misuse of an unauthorized disinfectant for therapeutic or medical purposes.

Hippocampal Transcriptome Changes After Subarachnoid Hemorrhage in Mice.

After subarachnoid hemorrhage (SAH), up to 95% of surviving patients suffer from post-SAH syndrome, which includes cognitive deficits with impaired memory, executive functions, and emotional disturbances. Although these long-term cognitive deficits are thought to result from damage to temporomesial-hippocampal areas, the underlying mechanisms remain unknown. To fill this gap in knowledge, we performed a systematic RNA sequencing screen of the hippocampus in a mouse model of SAH. SAH was induced by perforation of the circle of Willis in mice. Four days later, hippocampal RNA was obtained from SAH and control (sham perforation) mice. Next-generation RNA sequencing was used to determine differentially expressed genes in the whole bilateral hippocampi remote from the SAH bleeding site. Functional analyses and clustering tools were used to define molecular pathways. Differential gene expression analysis detected 642 upregulated and 398 downregulated genes (false discovery rate <0.10) in SAH compared to Control group. Functional analyses using IPA suite, Gene Ontology terms, REACTOME pathways, and MsigDB Hallmark gene set collections revealed suppression of oligodendrocytes/myelin related genes, and overexpression of genes related to complement system along with genes associated with innate and adaptive immunity, and extracellular matrix reorganization. Interferon regulatory factors, TGF-ß1, and BMP were identified as major orchestrating elements in the hippocampal tissue response. The MEME-Suite identified binding motifs of Krüppel-like factors, zinc finger transcription factors, and interferon regulatory factors as overrepresented DNA promoter motifs. This study provides the first systematic gene and pathway database of the hippocampal response after SAH. Our findings suggest that damage of the entorhinal cortex by subarachnoid blood may remotely trigger specific hippocampal responses, which include suppression of oligodendrocyte function. Identification of these novel pathways may allow for development of new therapeutic approaches for post-SAH cognitive deficits.

Speeding in the city of Xalapa, Mexico: Prevalence and associated factors.

OBJECTIVE: To estimate the prevalence of speeding in the city of Xalapa, Veracruz, in Mexico and to identify factors potentially associated to this risk behavior. METHODS: A cross-sectional study was conducted on December 2019 in Xalapa, Veracruz. Speed measurement was conducted in a random sample of 10% of all the main roads in the urban area (n = 12). Observations were conducted over the course of one week at different times spending no more than 1.5 h in each site at a time. All vehicles circulating in each observation site during the data collection were included in the sample. Characteristics of drivers, vehicles and the environment were also collected and analyzed, using logistic regression analysis and a multiple ordinal regression model to identify factors associated to speeding and more serious violations of speed limits. RESULTS: Average speed of the 3,390 vehicles observed was 50.97 km/h. Prevalence of speeding was 65.66% (95%-CI: 64.04-67.26%); 26.96% (95%-CI: 25.47-28.49) exceeded the speed limit by 50%. Speeding and more serious violations of speed limits were more frequent in light vehicles, residential zones and during weekends. More serious violations of speed limits were also more frequent on smaller roads, where speed limit were lower and during morning hours. CONCLUSIONS: The great majority of vehicles transgress speed limits in Xalapa, Veracruz. Our results support the urgent need to implement speed control measures in the city. Changes in road infrastructure design, as well as promoting a comprehensive speeding legislation (with adequate speed limits and correctly enforced) aimed at reducing exposure to this key risk factor are recommended. As evaluation of road safety interventions is key, our data could be used as a baseline to evaluate the effects and impact of future interventions implemented in this Mexican city.

Urinary MMP-9/UCr association with albumin concentration and albumin-creatinine-ratio in Mexican patients with type 2 diabetes mellitus.

BACKGROUND: Chronic kidney disease is one of the most common complications of type 2 diabetes mellitus (T2DM), causing an increased risk of cardiovascular morbidity and mortality. Matrix metalloproteinase (MMP) activity has been proposed as useful biomarker for diabetic renal and vascular complications. METHODS: A cross-sectional study was conducted among T2DM patients who attended a public secondary hospital in Mexico. We performed clinical, biochemical, and microbiological assessments, as well chronic kidney disease diagnosis according to the KDIGO guideline. Urinary MMP-9 was quantified by ELISA and adjusted using urinary creatinine (UCr). RESULTS: A total of 111 patients were included. Most participants were women (66%). Mean age was 61 ± 10 years and median T2DM duration was estimated at 11 years. Through multivariate analysis, MMP-9/UCr was found to be associated with albumin concentration and albumin to creatinine ratio. DISCUSSION: Validation of non-invasive biomarkers of chronic kidney disease among T2DM patients is necessary. Here, we demonstrate MMP-9/UCr as a potential biomarker of albumin concentration and albumin to creatinine ratio in Mexican patients with T2DM.

Caracterización epidemiológica de las exposiciones a dióxido de cloro/clorito de sodio en el contexto de la pandemia COVID-19: Reporte de los centros toxicológicos de América Latina / Epidemiological characterization of exposures to chlorine dioxide/ sodium chlorite in the context of the COVID-19 pandemic: Report of Poison Control Centers in Latin America

Resumen Los centros de información y asesoramiento toxicológico CIATs de América Latina, en el contexto de la pandemia de COVID-19, recibieron una serie de llamadas para consultas y asesoramientos relacionados con el uso de dióxido de cloro/clorito de sodio, que se estaban empleando en el tratamiento o prevención de dicha enfermedad. Dentro de la legislación vigente en los países de América Latina, no se contemplan productos farmacéuticos registrados para uso en humanos, ni se tiene evidencia de registros sanitarios en Europa, Canadá o Estados Unidos para tal fin, que contengan dióxido de cloro o clorito de sodio. Esta publicación, compila la información registrada como parte de la estadística del trabajo de ocho CIATs correspondientes a igual número de países de América Latina. Se identificó sexo, edad, sintomatología, circunstancia y grado de severidad de los 56 casos de pacientes intoxicados con dióxido de cloro/clorito de sodio registrados en el período del 15 de marzo al 30 de septiembre de 2020 en estos ocho países. Los resultados obtenidos confirman que la causa más común fue por mal uso, y el lugar de ocurrencia fue el hogar o sus alrededores, siendo el mayor porcentaje adultos jóvenes comprendidos entre 30 y 49 años. Los síntomas de intoxicación más frecuentemente encontrados fueron gastrointestinales, seguidos de cardiovasculares y respiratorios. La vía de ingreso al organismo en la mayoría de los casos fue por vía oral, reportándose algunos casos por vía inhalatoria, y en el 50% de los casos se constituyeron casos de severidad moderada, severa o fatal (3 fallecimientos). Este estudio contribuye a generar información relevante para las diferentes autoridades sanitarias, los ministerios de salud, las entidades encargadas de inspección, vigilancia y control de los países en los que se comercializan estos productos de manera ilegal por medio de redes sociales y promoviéndolos para uso en humanos para prevenir o curar COVID-19.

Abstract The Poison Control Centers in Latin America, in the context of COVID-19 pandemic, received a series of calls for consultations and recommendations related to the use of chlorine dioxide/sodium chlorite, in the treatment or prevention of CO-VID-19. Under current legislation in Latin America, no pharmaceutical products are registered for use in humans that contain chlorine dioxide or sodium chlorite, nor is there evidence of sanitary registries in Europe, Canada, or the United States for this purpose. This publication compiles the information registered by eight Poison Control Centers that correspond to the same number of Latin American countries. Sex, age, symptoms, circumstance, and degree of severity of the 56 cases of patients poisoned with chlorine dioxide/ sodium chlorite registered in the period from March 15th to September 30th, 2020 were identified. The results obtained confirm that the most common cause of poisoning was unintentional misuse, all of which occurred at home or its surroundings, with the highest percentage of registered cases being young adults between 30 and 49 years old. The most frequent symptoms of intoxication were gastrointestinal, followed by cardiovascular and respiratory. The route of exposure in most cases was oral, with some cases reported by inhalation; 48.2% of the cases were of moderate, severe, or fatal (3 deaths). This study contributes to the generation of relevant information for different health authorities, ministries of health, entities in charge of inspection, surveillance, and control in countries where these products are illegally marketed through social networks and promoted for use in humans to prevent or cure COVID-19.

Anti-biofilm effects and characterisation of the hydrogen peroxide activity of a range of Western Australian honeys compared to Manuka and multifloral honeys.

The antibacterial activity of honeys derived from the endemic flora of the southwest corner of Western Australia, including the trees Jarrah (Eucalyptus marginata) and Marri (Corymbia calophylla), remains largely unexplored. Investigation of these honeys showed minimum inhibitory concentrations (MICs) of 6.7-28.0% (w/v) against Gram positive and negative bacteria. Honey solutions showed enhanced antibacterial activity after hydrogen peroxide was allowed to accumulate prior to testing, with a mean MIC after accumulation of 14.3% compared to 17.4% before accumulation. Antibacterial activity was reduced after treatment with catalase enzyme, with a mean MIC of 29.4% with catalase compared to 15.2% without catalase. Tests investigating the role of the Gram negative outer membrane in honey susceptibility revealed increases in activity after destabilisation of the outer membrane. Honeys reduced both the formation of biofilm and the production of bacterial pigments, which are both regulated by quorum sensing. However, these reductions were closely correlated with global growth inhibition. Honey applied to existing biofilms resulted in decreased metabolic activity and minor decreases in viability. These results enhance our understanding of the mechanisms of antibacterial action of Jarrah and Marri honeys, and provide further support for the use of honey in the treatment of infected wounds.

La responsabilidad social corporativa y las tendencias de consumo de los millennials universitarios que laboran / Corporate social responsibility and consumption trends of working university millennial students

Resumen La responsabilidad social corporativa percibida se confirma vigente como un predictor significativo del comportamiento de compra. Sin embargo, existen variables intervinientes, como los buenos sentimientos, que llevan consigo características de disfrute, satisfacción y beneficio percibido, cuyos efectos pueden intensificar tal comportamiento. No obstante, este fenómeno no ha sido lo suficientemente estudiado en México. Por otra parte, las proyecciones demográficas sugieren que, en el mediano plazo, los mercados de consumo internacional y nacional estarán dominados por la generación millennial, con mayor énfasis, por quienes cuentan con un grado educativo superior y una ocupación laboral. El objetivo de la presente investigación fue determinar si la variable buenos sentimientos tiene efectos catalizadores en el consumo socialmente responsable de una muestra de jóvenes mexicanos millenials que estudian y laboran. Se encuestó a 97 estudiantes universitarios de una escuela de negocios del sur de Tamaulipas. Se empleó el modelo de regresión con mediación para explorar los efectos mediadores de buenos sentimientos en la relación entre la percepción de RSC y el consumo responsable. Los resultados indicaron que los buenos sentimientos, sí tienen efectos catalizadores positivos y significativos en el consumo de los estudiantes millennials mexicanos que trabajan, debido a la satisfacción, disfrute y el beneficio percibido que estos manifestaron al hacer consumos responsables a empresas con RSC.

Abstract Perceived corporate social responsibility (CSR) has been confirmed as a significant predictor of purchase behavior. Nevertheless, there are intervening variables such as "the good feelings" that involve characteristics of enjoyment, satisfaction and perceived benefit, whose effects can reinforce such behavior. In Mexico, these effects have not been sufficiently studied. Recent demographic projections, however, suggest that, in the mid-term, the national and international consumption market will be dominated by the millennial generation, especially by those who have a higher education degree and have already entered the labor market. Consequently, the objective of this article was to analyze if "the good feelings" variable increases the predictor effect of the perceived CSR on the social responsible purchase behavior. 97 university millennial students from a business school located on the southern region of Tamaulipas were surveyed. A regression model with mediation was employed to explore the mediating effects of the "good feelings" variable on the relationship between the perception of CSR and responsible consumption. The results indicated that "the good feelings" variable increases the positive and significant effect on the responsible consumption of the millennial Mexican students, due to the satisfaction, enjoyment and perceived benefit when consuming in a socially responsible way.

Association of urinary activity of MMP-9 with renal impairment in Mexican patients with type 2 diabetes mellitus.

BACKGROUND: Diabetic kidney disease is the most common cause of chronic kidney disease (CKD). An early event in diabetic kidney disease is alteration of the glomerular basement membrane and the mesangial expansion. Matrix metalloproteinases (MMP) are a family of endopeptidases responsible for controlling the pathophysiological remodeling of tissues, including renal tissues. MMP-9 in human urine has been proposed as a marker of diabetic nephropathy and urinary tract infections (UTI). METHODS: A cross-sectional study was conducted in type 2 diabetes mellitus (T2DM) patients who receive first level medical attention in Mexico. We used ELISA to measure MMP-9 levels in the urine of subjects with T2DM ≥ 18 years of age, who fulfilled the clinical requirements for calculation of glomerular filtration rate (GFR), according to the K/DOQI guide, in an attempt to identify whether MMP-9 levels in T2DM differ in patients with and without renal impairment. Univariate and multivariable analyses were performed in order to identify the association between MMP-9 and renal impairment. RESULTS: Included in the study were 34 (45%) subjects with renal impairment and 42 (55%) without. In the group with renal impairment, 10 subjects corresponded to stages 1-2 and 24 subjects corresponded to stage 3, according to their values of GFR and urinary albumin, following that proposed by the K/DOQI. No differences were found relating to sex, age, having or not having a partner, education, being able to read and write a message and duration of T2DM. Moreover, no differences were found between the groups in terms of weight, height, body mass index, waist size in general and frequency of UTI. In contrast, serum creatinine and urinary albumin were higher in the group with renal impairment, while GFR was greater in the group without renal impairment. Levels of MMP-9 were greater in women compared to men. Through univariate analysis in the general population, the presence of MMP-9 and that of its percentile 90 (P90) P90 were associated with the renal impairment group; however, in patients without UTI, only the presence of MMP-9 was associated with the renal impairment group, and no association was found with its P90. Multivariate analysis revealed an association between MMP-9 and its P90 with renal impairment. DISCUSSION: It is necessary to validate sensitive and non-invasive biological markers of CKD. We demonstrate that the presence and P90 of urinary MMP-9 are associated with renal impairment in Mexican patients with T2DM. While high levels of MMP-9 were associated to females and UTI, the presence of UTI was not associated with the incidence of renal impairment.

Association of Urinary Activity of MMP-2 with Microalbuminuria in an Isolated Sample of Subjects Living in High Altitude Rural Locations in México.

Hernández-Hernández, Magda Elena, Jaime Morales-Romero, Clara Luz Sampieri, Diego Jesús Luna Lozano, Isidra del Carmen Valencia Lezama, Mónica Janett Muñoz Contreras, and Arturo Rodríguez Hernández. Association of urinary activity of MMP-2 with microalbuminuria in an isolated sample of subjects living in high altitude rural locations in México. High Alt Med Biol. 18:209-218, 2017.-Matrix metalloproteinases (MMP) are implicated in remodeling of the renal extracellular matrix. In a cross-sectional study we evaluated renal impairment in general population of high-altitude rural locations in México. Multivariable analysis was performed to identify the association between MMP-2 and MMP-9 and microalbuminuria. Twenty-eight (20.9%) subjects with renal impairment (WRI) and 106 (79.1%) without renal impairment were included. No differences were found relating to sex, location, marital status, current habits, weight, height, body mass index, waist size in males, creatinine in males, and uric acid. In contrast, differences were found among age, level of education, waist size in general and in females, creatinine in general and in females, urinary albumin, urea, glucose, total cholesterol, and triglycerides. Proportions of hypertension, type 2 diabetes mellitus, central abdominal obesity, hypertriglyceridemia, and hypercholesterolemia were greater in the group WRI. Presence of urinary MMP-2 or of both urinary gelatinases and arbitrary unit (AU) values ≥P90 were associated with microalbuminuria. We conclude that AU values ≥P90 of urinary MMP-2 (OR = 20.1, p = 0.002) is associated with microalbuminuria.