Controlling heme redox properties in peptide amphiphile fibers with sequence and heme loading ratio.

Controlling the reduction midpoint potential of heme B is a key factor in many bioelectrochemical reactions, including long-range electron transport. Currently, there are a number of globular model protein systems to study this biophysical parameter; however, there are none for large polymeric protein model systems (e.g., the OmcS protein from G. sulfurreducens). Peptide amphiphiles, short peptides with a lipid tail that polymerize into fibrous structures, fill this gap. Here, we show a peptide amphiphile model system where one can tune the electrochemical potential of heme B by changing the loading ratio and peptide sequence. Changing the loading ratio resulted in the most significant increase, with values as high as -22 mV down to -224 mV. Circular dichroism spectra of certain sequences show Cotton effects at lower loading ratios that disappear as more heme B is added, indicating an ordered environment that becomes disrupted if heme B is overpacked. These findings can contribute to the design of functional self-assembling biomaterials.

Levels of persistent organic pollutants in cane toads (Rhinella marina) differ among sites with varying industrial and agricultural activities.

In this study, we captured cane toads (Rhinella marina) in four sites located in different regions affected by anthropogenic activities in Mexico. Subsequently we analyzed liver tissue for the presence of organochlorine pesticides (OCs) and polychlorinated biphenyls (PCBs) The levels of these POPs in the toads' livers ranged from 863.2 to 3109.6 ng/g of lipid weight across all sites. A multivariate statistical analysis highlighted two sites with the highest POPs levels, with the most polluted site displaying a high level of PCBs, suggesting influence of industrial activities. The second most polluted site displayed significant amounts of OCs, linking this location to agricultural activity. Additionally, we found pesticide metabolites and isomers that allowed us to distinguish past and recent exposure events. Our observations indicate that R. marina is suitable bioindicator of sites impacted by anthropogenic activities.

Cross-cultural adaptation of the FRAIL scale for critically ill patients in Spain.

AIM: To translate and culturally adapt the FRAIL scale into Spanish and perform a preliminary test of diagnostic accuracy in patients admitted to intensive care units. DESIGN: Cross-sectional diagnostic study. METHODS: Five intensive care units (ICU) in Spain were participated. Stage 1: Three native Spanish-speaking bilingual translators familiar with the field of critical care translated the scale from English into Spanish. Stage 2: Three native English-speaking bilingual translators familiar with critical care medicine. Stage 3: Authors of the original scale compared the English original and back-translated versions of the scale. Stage 4: Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the comprehension and relevance of each of the items of the Spanish version in 30 patients of 3 different age ranges (<50, 50-65 and >65 years). RESULTS: The FRAIL scale was translated and adapted cross-culturally for patients admitted to intensive care units in Spain. The process consisted of four stages: translation, back translation, comparison and pilot test. There was good correspondence between the original scale and the Spanish version in 100% of the items. The participating patients assessed the relevance (content validity) and comprehensibility (face validity) of each of the items of the first Spanish version. The relevance of some of the items scored low when the scale was used in patients younger than 65 years. CONCLUSIONS: We have cross-culturally adapted the FRAIL scale, originally in English, to Spanish for its use in the critical care medical setting in Spanish-speaking countries. IMPLICATIONS FOR PROFESSIONALS: Physicians and nurses can apply the new scale to all patients admitted to the intensive care units. Nursing care can be adapted according to frailty, trying to reduce the side effects of admission to these units for the most fragile patients. REPORTING METHOD: The manuscript's authors have adhered to the EQUATOR guidelines, using the COSMIN reporting guideline for studies on the measurement properties of patient-reported outcome measures. PATIENT OR PUBLIC CONTRIBUTION: In a pilot clinical study, we applied the first version of the FRAIL-Spain scale to intensive care unit (ICU) patients. Five nurses with more than 5 years of ICU experience and five critical care physicians assessed the relevance (content validity) and comprehensibility (face validity) of the five items of the first Spanish version. Relevance was assessed using a 4-point Likert scale ranging from 1 (no relevance) to 4 (high relevance), and comprehensibility was assessed as poor, acceptable or good. Each health professional applied the scale to three patients (total number of patients = 30) of three different age ranges (<50, 50-65 and >65 years) and recorded the time of application of the scale to each patient. Although the frailty scales were initially created by geriatricians to be applied to the elders, there is little experience with their application in critically ill patients of any age. Therefore, more information is needed to determine the relevance of using this scale in critical care patients. In this pilot study, we considered that nurses and critical care physicians should evaluate frailty using this adapted scale in adult patients admitted to the Intensive Care Units.

Knowledge of professionals about sexuality of the ostomyzed.

BACKGROUND: An ostomy significantly influences a person's life, altering their biopsychosocial and sexual sphere and affecting their interpersonal relationships. MATERIALS AND METHODS: Through an observational, descriptive, and cross-sectional study, with a questionnaire aimed at professionals from a health area in Madrid, we analyzed: sociodemographic variables, knowledge of the professionals on the subject, referral of the patient according to the professional's assessment and feelings that the subject under study produces in the patient and in professionals. RESULTS: 49% claimed to have no knowledge about sexuality of the ostomyzed patients. 55.9% of those surveyed consider that the healthcare provider is the one who should introduce the topic of sexuality during the clinical interview. 48.5 and 85.2% are unaware of treatments for male and female sexual dysfunction, respectively. CONCLUSIONS: The data show that the training provided in the university centers is insufficient to deal effectively with this issue in the medical consultation. The participants manifest null or minimal knowledge about the sexual sphere in ostomized patients. Knowledge deficiencies are detected in relation to the sexuality of the ostomized patient, difficulty in talking about sex with these patients, and the importance that sanitary professionals give to the patient's sexual sphere, among others.

ANTECEDENTES: Una ostomía influye significativamente en la vida de la persona, alterando su esfera biopsicosocial y sexual, y afectando a sus relaciones interpersonales. MATERIAL Y MÉTODO: Estudio observacional, descriptivo y transversal. Mediante un cuestionario dirigido a profesionales de un área sanitaria de Madrid, se analizan variables sociodemográficas, conocimientos de los profesionales, derivación del paciente a un especialista según la valoración del profesional encuestado y sentimientos que produce en ellos el tema de estudio. RESULTADOS: El 49% afirma tener conocimientos nulos sobre la sexualidad del paciente ostomizado. El 55.9% de los encuestados considera que el sanitario es quien debe introducir el tema de la sexualidad durante la entrevista clínica. El 48.5 y el 85.2% desconocen tratamientos para la disfunción sexual, masculina y femenina, respectivamente. CONCLUSIÓN: Los datos demuestran que la formación impartida en los centros universitarios es insuficiente para tratar de forma efectiva este tema en la consulta. Los participantes en el estudio muestran nulo o mínimo conocimiento sobre la esfera sexualidad en el paciente ostomizado Se detectan deficiencias de conocimiento en relación con la sexualidad del ostomizado, dificultad para hablar de sexo con el paciente y valor que da el profesional a la esfera sexual en su paciente, entre otras.

CRISPR/dCAS9-mediated DNA demethylation screen identifies functional epigenetic determinants of colorectal cancer.

BACKGROUND: Promoter hypermethylation of tumour suppressor genes is frequently observed during the malignant transformation of colorectal cancer (CRC). However, whether this epigenetic mechanism is functional in cancer or is a mere consequence of the carcinogenic process remains to be elucidated. RESULTS: In this work, we performed an integrative multi-omic approach to identify gene candidates with strong correlations between DNA methylation and gene expression in human CRC samples and a set of 8 colon cancer cell lines. As a proof of concept, we combined recent CRISPR-Cas9 epigenome editing tools (dCas9-TET1, dCas9-TET-IM) with a customized arrayed gRNA library to modulate the DNA methylation status of 56 promoters previously linked with strong epigenetic repression in CRC, and we monitored the potential functional consequences of this DNA methylation loss by means of a high-content cell proliferation screen. Overall, the epigenetic modulation of most of these DNA methylated regions had a mild impact on the reactivation of gene expression and on the viability of cancer cells. Interestingly, we found that epigenetic reactivation of RSPO2 in the tumour context was associated with a significant impairment in cell proliferation in p53-/- cancer cell lines, and further validation with human samples demonstrated that the epigenetic silencing of RSPO2 is a mid-late event in the adenoma to carcinoma sequence. CONCLUSIONS: These results highlight the potential role of DNA methylation as a driver mechanism of CRC and paves the way for the identification of novel therapeutic windows based on the epigenetic reactivation of certain tumour suppressor genes.

Multi-omic integration of DNA methylation and gene expression data reveals molecular vulnerabilities in glioblastoma.

Glioblastoma (GBM) is one of the most aggressive types of cancer and exhibits profound genetic and epigenetic heterogeneity, making the development of an effective treatment a major challenge. The recent incorporation of molecular features into the diagnosis of patients with GBM has led to an improved categorization into various tumour subtypes with different prognoses and disease management. In this work, we have exploited the benefits of genome-wide multi-omic approaches to identify potential molecular vulnerabilities existing in patients with GBM. Integration of gene expression and DNA methylation data from both bulk GBM and patient-derived GBM stem cell lines has revealed the presence of major sources of GBM variability, pinpointing subtype-specific tumour vulnerabilities amenable to pharmacological interventions. In this sense, inhibition of the AP-1, SMAD3 and RUNX1/RUNX2 pathways, in combination or not with the chemotherapeutic agent temozolomide, led to the subtype-specific impairment of tumour growth, particularly in the context of the aggressive, mesenchymal-like subtype. These results emphasize the involvement of these molecular pathways in the development of GBM and have potential implications for the development of personalized therapeutic approaches.

Nicotinamide N-methyltransferase (NNMT) regulates the glucocorticoid signaling pathway during the early phase of adipogenesis.

Obesity is associated with adipose tissue dysfunction through the differentiation and expansion of pre-adipocytes to adipocytes (hyperplasia) and/or increases in size of pre-existing adipocytes (hypertrophy). A cascade of transcriptional events coordinates the differentiation of pre-adipocytes into fully differentiated adipocytes; the process of adipogenesis. Although nicotinamide N-methyltransferase (NNMT) has been associated with obesity, how NNMT is regulated during adipogenesis, and the underlying regulatory mechanisms, remain undefined. In present study we used genetic and pharmacological approaches to elucidate the molecular signals driving NNMT activation and its role during adipogenesis. Firstly, we demonstrated that during the early phase of adipocyte differentiation NNMT is transactivated by CCAAT/Enhancer Binding Protein beta (CEBPB) in response to glucocorticoid (GC) induction. We found that Nnmt knockout, using CRISPR/Cas9 approach, impaired terminal adipogenesis by influencing the timing of cellular commitment and cell cycle exit during mitotic clonal expansion, as demonstrated by cell cycle analysis and RNA sequencing experiments. Biochemical and computational methods showed that a novel small molecule, called CC-410, stably binds to and highly specifically inhibits NNMT. CC-410 was, therefore, used to modulate protein activity during pre-adipocyte differentiation stages, demonstrating that, in line with the genetic approach, chemical inhibition of NNMT at the early stages of adipogenesis impairs terminal differentiation by deregulating the GC network. These congruent results conclusively demonstrate that NNMT is a key component of the GC-CEBP axis during the early stages of adipogenesis and could be a potential therapeutic target for both early-onset obesity and glucocorticoid-induced obesity.

Potentially inappropriate prescriptions in geriatric patients hospitalized in the internal medicine department of a referral hospital in Mexico.

BACKGROUND: Potentially inappropriate prescription (PIP) constitutes a risk for the development of adverse effects of a drug that outweigh its benefits, which can be considered inappropriate medication use. OBJECTIVE: To describe the prevalence of PIP in geriatric patients hospitalized at the internal medicine department of a referral hospital in Mexico. MATERIAL AND METHODS: Cross-sectional, descriptive design, with simple allocation of medical records from patients older than 65 years hospitalized between January 2016 and August 2017. The STOPP/START criteria were applied to identify the number of PIPs, the number of prescribed medications, number and type of comorbidities, as well as days of hospital stay. RESULTS: A prevalence of PIP of 73.3% was identified, with main comorbidities being hypertension and type 2 diabetes mellitus. A total of 1,885 prescribed medications were quantified; mean hospital stay was 6.3 days. CONCLUSIONS: A high prevalence of PIP was identified in hospitalized geriatric patients, hence the importance of applying the STOPP/START criteria and of the role of the pharmacist for validating the prescription prior to drug administration.

ANTECEDENTES: Una prescripción potencialmente inapropiada (PPI) constituye un riesgo de presentar efectos adversos por un fármaco que superan los beneficios de este, pudiendo considerarse como uso inadecuado de medicamentos. OBJETIVO: Describir la prevalencia de prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna de un hospital de referencia en México. MATERIAL Y MÉTODOS: Diseño descriptivo transversal, con asignación simple de expedientes clínicos de pacientes hospitalizados mayores de 65 años, entre enero de 2016 y agosto de 2017. Se aplicaron los criterios STOPP y START para identificar el número de PPI, cantidad de medicamentos prescritos, presencia, cantidad y tipo de comorbilidades, así como días de estancia hospitalaria. RESULTADOS: Se encontró una prevalencia de 73.3 % de PPI y las principales comorbilidades fueron hipertensión arterial y diabetes mellitus tipo 2. Se cuantificaron 1885 medicamentos prescritos; la estancia hospitalaria media fue de 6.3 días. CONCLUSIONES: Se identificó alta prevalencia de PPI en los pacientes geriátricos hospitalizados, de ahí la importancia de aplicar los criterios STOPP y START y del papel del farmacéutico en la validación de la prescripción antes de la administración de medicamentos.

Prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna en un hospital de referencia en México / Potentially inappropriate prescriptions in geriatric patients hospitalized in the internal medicine department of a referral hospital in Mexico

Resumen Antecedentes: Una prescripción potencialmente inapropiada (PPI) constituye un riesgo de presentar efectos adversos por un fármaco que superan los beneficios de este, pudiendo considerarse como uso inadecuado de medicamentos. Objetivo: Describir la prevalencia de prescripciones potencialmente inapropiadas en pacientes geriátricos hospitalizados en el servicio de medicina interna de un hospital de referencia en México. Material y métodos: Diseño descriptivo transversal, con asignación simple de expedientes clínicos de pacientes hospitalizados mayores de 65 años, entre enero de 2016 y agosto de 2017. Se aplicaron los criterios STOPP y START para identificar el número de PPI, cantidad de medicamentos prescritos, presencia, cantidad y tipo de comorbilidades, así como días de estancia hospitalaria. Resultados: Se encontró una prevalencia de 73.3 % de PPI y las principales comorbilidades fueron hipertensión arterial y diabetes mellitus tipo 2. Se cuantificaron 1885 medicamentos prescritos; la estancia hospitalaria media fue de 6.3 días. Conclusiones: Se identificó alta prevalencia de PPI en los pacientes geriátricos hospitalizados, de ahí la importancia de aplicar los criterios STOPP y START y del papel del farmacéutico en la validación de la prescripción antes de la administración de medicamentos.

Abstract Background: Potentially inappropriate prescription (PIP) constitutes a risk for the development of adverse effects of a drug that outweigh its benefits, which can be considered inappropriate medication use. Objective: To describe the prevalence of PIP in geriatric patients hospitalized at the internal medicine department of a referral hospital in Mexico. Material and methods: Cross-sectional, descriptive design, with simple allocation of medical records from patients older than 65 years hospitalized between January 2016 and August 2017. The STOPP/START criteria were applied to identify the number of PIPs, the number of prescribed medications, number and type of comorbidities, as well as days of hospital stay. Results: A prevalence of PIP of 73.3% was identified, with main comorbidities being hypertension and type 2 diabetes mellitus. A total of 1,885 prescribed medications were quantified; mean hospital stay was 6.3 days. Conclusions: A high prevalence of PIP was identified in hospitalized geriatric patients, hence the importance of applying the STOPP/START criteria and of the role of the pharmacist for validating the prescription prior to drug administration.

Health Risk Assessment in Mexican Children Exposed to Fluoride from Sweetened Beverages.

The primary source of fluoride exposure is groundwater, but evidence suggests that beverages and food are additional fluoride sources. Intake of these products at an early age affects the optimal functioning of soft organs. An increase in sweetened beverage consumption by the pediatric population has been reported, suggesting an increase in fluoride exposure. The objectives of this study were to determine the fluoride concentrations in beverages and analyze the risk to human health from fluoride exposure to sweetened beverages consumed by children. Eighty-two sugar-sweetened beverages produced in different Mexican states were analyzed. The fluoride determination was carried out with an ion-selective electrode. The highest fluoride concentration was 1.92 mg/L; 73.2% of beverages showed fluoride values above permitted limits. Low-cost beverages had the highest fluoride values, suggesting that the water used for their production does not comply with fluorine regulations. According to the risk assessment in children from 3 to 6 years, the daily consumption of juices and sodas with concentrations that exceeded the normative of 0.7 mg/L could represent a risk to dental fluorosis development. It is crucial to control fluoride and regulate its concentrations in beverages for children to ensure food safety, especially in areas of endemic hydrofluorosis.

Epidemiology of Fabry disease in patients in hemodialysis in the Madrid community.

This study screened for Fabry disease (FD) in patients in hemodialysis (HD) in the region of Madrid (CAM) with a cross-sectional design to evaluate HD-prevalent patients, followed by a three-year period prospective design to analyze HD-incident patients. INCLUSION CRITERIA: patients older than 18 years on HD in the CAM, excluding patients diagnosed with any other hereditary disease with renal involvement different from FD, that sign the Informed Consent (IC). EXCLUSION CRITERIA: underaged patients or not agreeing or not being capable of signing the IC. RESULTS: 3470 patients were included, 63% males and with an average age of 67.9±9.7 years. 2357 were HD-prevalent patients and 1113 HD-incident patients. For HD-prevalent patients, average time in HD was 45.2 months (SD 51.3), in HD-incident patients proteinuria was present in 28.4%. There were no statistical differences in plasmatic alpha-galactosidase A (α-GAL-A) activity or Lyso-GL-3 values when comparing HD-prevalent and HD-incident populations and neither between males and females. A genetic study was performed in 87 patients (2.5% of patients): 60 male patients with decreased enzymatic activity and 27 female patients either with a decreased GLA activity, increased Lyso-Gl3 levels or both. The genetic variants identified were: p.Asp313Tyr (4 patients), p.Arg220Gln (3 patients) and M290I (1 patient). None of the identified variants is pathogenic. CONCLUSIONS: 76% of HD Centers of the CAM participated in the study. This is the first publication to describe the prevalence of FD in the HD-population of a region of Spain as well as its average α-GAL-A-activity and plasmatic Lyso-Gl3 levels. It is also the first study that combines a cross-sectional design with a prospective follow-up design. This study has not identified any FD patient.

Cyclic Vomiting Syndrome: An underdiagnosed entity. Report of a case

Cyclic vomiting syndrome is a benign, chronic, functional gastrointestinal pathology that manifests clinically with intense nausea and vomiting interspersed with asymptomatic periods. Its diagnosis is made according to the Rome IV criteria, which require the presence of at least 2 episodes of vomiting in the past 6 months or 3 or more episodes in the past year, with the corresponding exclusion of secondary causes that can explain the vomiting. We present the case of a 44-year-old man who consulted for intermittent nausea and vomiting of 1 year evolution with hydroelectrolytic repercussion and multiple emergency consultations. The diagnosis of cyclic vomiting syndrome was made and treatment with amitriptyline was started due to its neuromodulatory effect to prevent the recurrence of episodes. After 6 months of establishing it, the patient is asymptomatic.

El síndrome de vómitos cíclicos es una patología gastrointestinal funcional crónica, benigna, que se manifiesta clínicamente con náuseas y vómitos intensos que intercalan con periodos asintomáticos. Su diagnóstico se realiza de acuerdo con los criterios de Roma IV, que requieren la presencia de al menos 2 episodios de vómitos en los últimos 6 meses o 3 o más episodios en el último año, con la correspondiente exclusión de causas secundarias que puedan explicar los síntomas. Se presenta el caso de un hombre de 44 años que consulta por náuseas y vómitos intermitentes de 1 año de evolución, con repercusión hidroelectrolítica y múltiples consultas en emergencia. Se realiza el diagnóstico de síndrome de vómitos cíclicos y se inicia tratamiento con amitriptilina, por su efecto neuromodulador para prevenir la recurrencia de los episodios. Luego de 6 meses de instaurado el mismo, el paciente se presenta asintomático.

Comprehensive Approach to Genomic and Immune Profiling: Insights of a Real-World Experience in Gynecological Tumors.

Gynecological cancer accounts for an elevated incidence worldwide requiring responsiveness regarding its care. The comprehensive genomic approach agrees with the classification of certain tumor types. We evaluated 49 patients with gynecological tumors undergoing high-throughput sequencing to explore whether identifying alterations in cancer-associated genes could characterize concrete histological subtypes. We performed immune examination and analyzed subsequent clinical impact. We found 220 genomic aberrations mostly distributed as single nucleotide variants (SNV, 77%). Only 3% were classified as variants of strong clinical significance in BRCA1 and BRCA2 of ovarian high-grade serous (HGSC) and uterine endometrioid carcinoma. TP53 and BRCA1 occurred in 72% and 28% of HGSC. Cervical squamous cell carcinoma was entirely HPV-associated and mutations occurred in PIK3CA (60%), as well as in uterine serous carcinoma (80%). Alterations were seen in PTEN (71%) and PIK3CA (60%) of uterine endometrioid carcinoma. Elevated programmed death-ligand 1 (PD-L1) was associated with high TILs. Either PD-L1 augmented in deficient mis-matched repair (MMR) proteins or POLE mutated cases when compared to a proficient MMR state. An 18% received genotype-guided therapy and a 4% immunotherapy. The description of tumor subtypes is plausible through high-throughput sequencing by recognizing clinically relevant alterations. Additional concomitant assessment of immune biomarkers identifies candidates for immunotherapy.

Enhanced Detection of Viral RNA Species Using FokI-Assisted Digestion of DNA Duplexes and DNA/RNA Hybrids.

The accurate detection of nucleic acids from certain biological pathogens is critical for the diagnosis of human diseases. However, amplified detection of RNA molecules from a complex sample by direct detection of RNA/DNA hybrids remains a challenge. Here, we show that type IIS endonuclease FokI is able to digest DNA duplexes and DNA/RNA hybrids when assisted by a dumbbell-like fluorescent sensing oligonucleotide. As proof of concept, we designed a battery of sensing oligonucleotides against specific regions of the SARS-CoV-2 genome and interrogated the role of FokI relaxation as a potential nicking enzyme for fluorescence signal amplification. FokI-assisted digestion of SARS-CoV-2 probes increases the detection signal of ssDNA and RNA molecules and decreases the limit of detection more than 3.5-fold as compared to conventional molecular beacon approaches. This cleavage reaction is highly specific to its target molecules, and no detection of other highly related B-coronaviruses was observed in the presence of complex RNA mixtures. In addition, the FokI-assisted reaction has a high multiplexing potential, as the combined detection of different viral RNAs, including different SARS-CoV-2 variants, was achieved in the presence of multiple combinations of fluorophores and sensing oligonucleotides. When combined with isothermal rolling circle amplification technologies, FokI-assisted digestion reduced the detection time of SARS-CoV-2 in COVID-19-positive human samples with adequate sensitivity and specificity compared to conventional reverse transcription polymerase chain reaction approaches, highlighting the potential of FokI-assisted signal amplification as a valuable sensing mechanism for the detection of human pathogens.

Mental Health Day Hospitals and Lockdown Due to COVID-19 in Spain.

Introduction: The COVID-19 pandemic has forced changes in patient care in Mental Health Day Hospitals (MHDHs). Objectives: To study the interventions performed in MHDHs during the pandemic in comparison with those performed in other facilities and to analyze the new hospital admissions in both groups. Method: A retrospective multicenter cohort study comparing the interventions received by a group of 161 patients admitted in MHDHs during the lockdown period in Spain with the interventions of another group of 109 patients who were treated at other facilities during lockdown. Results: MHDHs reduced their face-to-face interventions during lockdown just as much as other facilities but implemented telematic intervention methods to a greater extent. Patients attached to MHDHs during lockdown were admitted significantly less and presented fewer urgent consultations in the following 6 months. Conclusion: The use of telepsychiatry made it feasible to adapt MHDHs to periods of lockdown, being useful to improve the continuity of care during the pandemic. In addition, it was possible to maintain a reduction in hospital admissions in patients treated at MHDHs.

Antioxidant and Anti-Inflammatory Effects of Coenzyme Q10 Supplementation on Infectious Diseases.

With the appearance of new viruses and infectious diseases (ID) such as COVID-19 in 2019, as well as the lack of specific pharmacological tools for the management of patients with severe complications or comorbidities, it is important to search for adjuvant treatments that help improve the prognosis of infectious disease patients. It is also important that these treatments limit the oxidative and hyperinflammatory damage caused as a response to pathogenic agents, since, in some cases, an inflammatory syndrome may develop that worsens the patient's prognosis. The potential benefits of complementary nutrients and dietary interventions in the treatment of pathological processes in which oxidative stress and inflammation play a fundamental role have been widely evaluated. Coenzyme Q10 (CoQ10) is a supplement that has been shown to protect cells and be effective in cardiovascular diseases and obesity. Additionally, some studies have proposed it as a possible adjuvant treatment in viral infections. Preclinical and clinical studies have shown that CoQ10 has anti-inflammatory and antioxidant effects, and effects on mitochondrial dysfunction, which have been linked to the inflammatory response.

Social and environmental conflicts caused by agrochemical use in Salta, Santiago del Estero and Santa Fe, Argentina. / Conflictividad socio-ambiental por uso de agroquímicos en Salta, Santiago del Estero y Santa Fe, Argentina.

The purpose of this article is to contribute to the understanding and visibility of conflicts and disputes over the use of agrochemicals in the provinces of Santa Fe, Santiago del Estero and Salta, in Argentina. Secondary information sources were gathered and systematized to perform a first contextual analysis of regulatory frameworks, public policies and the emergence of social construction processes related to environmental and health risks. This analysis revolved around three dimensions: a regulatory dimension, a political-institutional dimension, and a territorial-health dimension. In all three jurisdictions, there are specific laws that govern the use of agrochemicals and certain institutionalization intended to implement, control and monitor them. However, similarly to what has happened at the regional and international levels, the study revealed multiple conflict situations and/or events that call environmental and health impacts into question. Agrochemical use policy is shattered into multiple regulations, institutions and levels of competence, a framework in which health and environmental policies are left behind. Despite some progress, there is no official recognition of the health and environmental damage caused by the use of agrochemicals.

El objetivo del artículo es contribuir a la comprensión y visibilización de los conflictos y controversias en torno al uso de agroquímicos en las provincias de Santa Fe, Santiago del Estero y Salta, Argentina. Se relevaron y sistematizaron fuentes de información secundaria, con el fin de llevar adelante un primer análisis contextual de los marcos regulatorios, las políticas públicas y la emergencia de procesos de construcción social de los riesgos ambientales y sanitarios. El análisis fue organizado en torno a tres dimensiones: normativa, político-institucional y territorial-sanitaria. En las tres jurisdicciones existen leyes específicas que regulan el uso de agroquímicos y cierta institucionalidad destinada a su implementación, control y monitoreo. No obstante, y en concordancia con lo ocurrido a nivel regional e internacional, el estudio relevó una multiplicidad de situaciones y/o eventos conflictivos que problematizan los impactos ambientales y sanitarios. La política relativa a la utilización de agroquímicos está fragmentada en múltiples regulaciones, instituciones y escalas de competencias, marco dentro del cual la política sanitaria y ambiental poseen un lugar rezagado. Más allá de ciertos avances, no hay reconocimiento oficial del daño a la salud y el ambiente generado por el uso de agroquímicos.

Conflictividad socio-ambiental por uso de agroquímicos en Salta, Santiago del Estero y Santa Fe, Argentina / Social and environmental conflicts caused by agrochemical use in Salta, Santiago del Estero and Santa Fe, Argentina

Resumen El objetivo del artículo es contribuir a la comprensión y visibilización de los conflictos y controversias en torno al uso de agroquímicos en las provincias de Santa Fe, Santiago del Estero y Salta, Argentina. Se relevaron y sistematizaron fuentes de información secundaria, con el fin de llevar adelante un primer análisis contextual de los marcos regulatorios, las políticas públicas y la emergencia de procesos de construcción social de los riesgos ambientales y sanitarios. El análisis fue organizado en torno a tres dimensiones: normativa, político-institucional y territorial-sanitaria. En las tres jurisdicciones existen leyes específicas que regulan el uso de agroquímicos y cierta institucionalidad destinada a su implementación, control y monitoreo. No obstante, y en concordancia con lo ocurrido a nivel regional e internacional, el estudio relevó una multiplicidad de situaciones y/o eventos conflictivos que problematizan los impactos ambientales y sanitarios. La política relativa a la utilización de agroquímicos está fragmentada en múltiples regulaciones, instituciones y escalas de competencias, marco dentro del cual la política sanitaria y ambiental poseen un lugar rezagado. Más allá de ciertos avances, no hay reconocimiento oficial del daño a la salud y el ambiente generado por el uso de agroquímicos.

Abstract The purpose of this article is to contribute to the understanding and visibility of conflicts and disputes over the use of agrochemicals in the provinces of Santa Fe, Santiago del Estero and Salta, in Argentina. Secondary information sources were gathered and systematized to perform a first contextual analysis of regulatory frameworks, public policies and the emergence of social construction processes related to environmental and health risks. This analysis revolved around three dimensions: a regulatory dimension, a political-institutional dimension, and a territorial-health dimension. In all three jurisdictions, there are specific laws that govern the use of agrochemicals and certain institutionalization intended to implement, control and monitor them. However, similarly to what has happened at the regional and international levels, the study revealed multiple conflict situations and/or events that call environmental and health impacts into question. Agrochemical use policy is shattered into multiple regulations, institutions and levels of competence, a framework in which health and environmental policies are left behind. Despite some progress, there is no official recognition of the health and environmental damage caused by the use of agrochemicals.

Cyclic Vomiting Syndrome: An underdiagnosed entity. Report of a case.

Cyclic vomiting syndrome is a benign, chronic, functional gastrointestinal pathology that manifests clinically with intense nausea and vomiting interspersed with asymptomatic periods. Its diagnosis is made according to the Rome IV criteria, which require the presence of at least 2 episodes of vomiting in the past 6 months or 3 or more episodes in the past year, with the corresponding exclusion of secondary causes that can explain the vomiting. We present the case of a 44-year-old man who consulted for intermittent nausea and vomiting of 1 year evolution with hydroelectrolytic repercussion and multiple emergency consultations. The diagnosis of cyclic vomiting syndrome was made and treatment with amitriptyline was started due to its neuromodulatory effect to prevent the recurrence of episodes. After 6 months of establishing it, the patient is asymptomatic.