EFECTOS DE DIETAS RICAS EN FRUCTOSA AÑADIDA EN LA PATOGÉNESIS DEL HÍGADO GRASO NO ALCOHÓLICO / EFFECTS OF DIETS RICH IN ADDED FRUCTOSE ON THE PATHOGENESIS OF NON-ALCOHOLIC FATTY LIVER DISEASE

Introducción: El hígado graso no alcohólico se enmarca en un grupo de patologías de etiología multifactorial, en el que la alimentación tendría un papel protagónico. En este sentido, el consumo de dietas ricas en fructosa, en especial a partir de fructosa añadida o jarabe de maíz alto en fructosa, ha sido motivo de investigación por su probable rol en la patogénesis de esta enfermedad. Metodología: Se realizó una búsqueda de artículos en relación con los efectos de las dietas ricas en fructosa sobre parámetros que podrían afectar la esteatosis hepática con el objetivo de organizar las principales evidencias al respecto. Resultados: Los estudios analizados tienden a evidenciar asociaciones positivas entre estas dietas y un mayor riesgo de desarrollar disbiosis intestinal, pérdida de integridad de la barrera intestinal y esteatosis hepática. Conclusiones: Los antecedentes recopilados en la presente revisión muestran evidencia de que este tipo de dietas favorecerían una serie de eventos que pueden conducir al hígado graso no alcohólico; por lo tanto, procurar un consumo adecuado de este monosacárido representaría una interesante alternativa de prevención para esta patología

Introduction: The non-alcoholic fatty liver disease falls within the group of multifactorial etiology pathologies in which food would play an important role. It is in this regard that the consumption of diets rich in fructose, especially from added fructose or corn syrup in fructose, has been a subject of investigation due to its likely roll in the pathogenesis of this disease. Methodology: A research for articles was performed about the effects of very rich fructose diets on parameters who could affect the liver steatosis in order to organize the main evidences. Results: The studies analized tend to report positive association between this diets and a higher risk of intestinal dysbiosis, intestinal barrier loss and partially with increased hepatic steatosis. Conclusions: The records compiled in the present review show evidence that this type of diets promote a serie of events that could result in non-alcoholic fatty liver disease so try a adequate consumption of this monosaccharides it would represent an interesting alternative to prevent this pathology

Association between bacterial community and cadmium distribution across Colombian cacao crops.

Assessing the bacterial community composition across cacao crops is important to understand its potential role as a modulator of cadmium (Cd) translocation to plant tissues under field conditions; Cd mobility between soil and plants is a complex and multifactorial problem that cannot be captured only by experimentation. Although microbes have been shown to metabolize and drive the speciation of Cd under controlled conditions, regardless of the link between soil bacterial community (SBC) dynamics and Cd mobilization in the rhizosphere, only a few studies have addressed the relationship between soil bacterial community composition (SBCC) and Cd content in cacao seeds (Cdseed). Therefore, this study aimed to explore the association between SBCC and different factors influencing the distribution of Cd across cacao crop systems. This study comprised 225 samples collected across five farms, where we used an amplicon sequencing approach to characterize the bacterial community composition. The soil Cd concentration alone (Cdsoil) was a poor predictor of Cdseed. Still, we found that this relationship was more apparent when the variation within farms was controlled, suggesting a role of heterogeneity within farms in modulating Cd translocation and, thus, seed Cd content. Our results provide evidence of the link between soil bacterial communities and the distribution of Cd across Colombian cacao crops, and highlight the importance of incorporating fine-spatial-scale studies to advance the understanding of factors driving Cd uptake and accumulation in cacao plants. IMPORTANCE: Cadmium (Cd) content in cacao crops is an issue that generates interest due to the commercialization of chocolate for human consumption. Several studies provided evidence about the non-biological factors involved in its translocation into the cacao plant. However, factors related to this process, including soil bacterial community composition (SBCC), still need to be addressed. It is well known that soil microbiome could impact compounds' chemical transformation, including Cd, on the field. Here, we found the first evidence of the link between soil bacterial community composition and Cd concentration in cacao soils and seeds. It highlights the importance of including the variation of bacterial communities to assess the factors driving the Cd translocation into cacao seeds. Moreover, the results highlight the relevance of the spatial heterogeneity within and across cacao farms, influencing the variability of Cd concentrations.

Assessing the cadmium content of cacao crops in Arauca, Colombia.

The district of Arauca is the second-largest producer of cacao in Colombia. However, despite its quality, it faces issues for export due to levels of cadmium (Cd) higher than the regulatory thresholds. A central question is how it may impact agricultural performance in the presence of Cd in cacao and chocolates. This study quantified Cd in cacao plantations from Arauca. Thus, 180 farms were assessed in the municipalities of Arauquita, Fortul, Saravena, and Tame. Five sample types (soil, irrigation channel sediment, soil litter, cacao seeds, and chocolates) were assessed for Cd. As a technological innovation, the new MXRF technology was used for Cd in chocolates. The sequence of Cd content was soil litter > chocolate > soils > cacao seeds > irrigation-channel sediment. A gradient north-south of Cd content in soil was observed, where highest content was found in farms near the Arauca River, and lower farther away. In irrigation channel sediment, Cd levels averaged 0.07 mg kg-1. The Cd content in cacao seeds was 0.78 mg kg-1 on average. Cd content in chocolates was above the threshold (1.10 mg kg-1 on average, including several cacao mass percentages). These artisanal chocolate bars produced by single farms were near the limit of Cd set by the European Union (up to 0.8 mg kg-1). Therefore, mixing beans from different farms could reduce their Cd content. The present study underscores the complexity of Cd distribution, emphasizing the importance of integrating soil, crop, and landscape features in managing and mitigating Cd levels in cacao.

Impact of Insurance Type on Access to Pain Management Specialists for the Treatment of Lower Back Pain.

Background Low back pain is known to be one of the leading causes of disability among the young and elderly population. Low back pain can stem from multiple sources, including spinal degeneration, injury, herniated discs, sciatica, and other contributing causes. This symptom significantly influences the quality of life of affected individuals. Its implications include extensive social and economic costs. Economic considerations arise from the fact that not all healthcare facilities accept the insurance plans available to retired individuals under Medicare. This places an additional burden on patients who must bear the financial responsibility for healthcare services not covered by their insurance plan. Florida, renowned as a favored state for retirement, consists of a demographic composition wherein 21% of its residents are aged 65 or older. A significant proportion of this demographic qualifies for Traditional Medicare (TM) and/or Medicare Advantage (MA) plans. Thus, understanding the disparities in healthcare access between Medicare and Medicare Advantage plans is crucial. This study aims to evaluate different Medicare insurances available in the market and their impact on the ease of accessibility to pain management specialists for the treatment of lower back pain in Florida patients. Methods We analyzed the Florida Department of Health database to identify the four counties in Florida with the highest Medicare enrollment rates in 2022: Miami-Dade, Palm Beach, Broward, and Pinellas County. Using the U.S. News and Report directory, 25 Pain Management-trained anesthesiologists were randomly selected from each of the four counties. Each office was contacted four times via telephone by four different team members to assess appointment availability for a fictional 65-year-old grandfather seeking treatment for chronic low back pain. The study examined appointment availability and accepted insurance types, including Cigna (commercial insurance), TM, Humana Gold Plus HMO (Medicare Advantage plan), and Blue Medicare Select PPO (Medicare Advantage plan). Practices without contact information or retired physicians were excluded from the analysis. Time to appointment was measured in business days. Results Of the 100 Pain Management Physicians contacted, 44 fit the inclusion criteria of being non-retired physicians, still practicing in one of the four counties with open offices and valid contact information. Blue Medicare Select PPO was accepted by 47.73%, Humana Gold Plus HMO by 56.82%, TM by 93.18%, and Cigna by 93.18% of the encounters. Blue Medicare select PPO and Humana Gold Plus HMO were accepted at significantly lower rates when compared to Traditional Medicare and Cigna with P values of P < .00001 and P < .000176, respectively. There was no significant difference found in the time to appointment between insurances with P value < 7. Conclusion The study found that patients enrolled in Medicare Advantage plans have significantly decreased access to care when compared to those enrolled in TM or commercial insurance. Further research is needed to elucidate the reasons behind differences in access to care across different insurances, as identified in the study.

Cacao (Theobromacacao L.) climate zones and its associated agrobiodiversity in Arauca, Colombia.

Background: Cacao (Theobromacacao L) is one of the most relevant crops in terms of economy and social rural development in Colombia. Cacao is also an important crop due to its potential to replace illicit crops and it is related to less deforestation and preserves the biodiversity. There are several cacao districts in Colombia, one of these being Arauca. The Department of Arauca is the second largest cocoa producing region in Colombia; however, it is heavily affected by armed conflict. To raise the knowledge and technology available in the region, integrating data on the occurrence of cacao farms with climatic variables becomes a powerful socioeconomic mapping tool for maintaining agrobiodiversity and food security in the region. Consequently, this type of agrodiversity data and agroclimatic approaches help to better manage agrobiodiversity, as in the cacao region of Arauca. These tools are even more relevant in biodiverse regions, such as flooded savannahs and tropical forest ecosystems, which are currently undergoing drastic changes due to agricultural expansion and climate change. One of the knowledge gaps in Colombia´s cacao regions is that there are currently no agroclimatic maps made with a social and scientific approach. This study aimed to provide a database of the spatial distribution of cacao farms in Arauca, as well as agroclimatic maps that identify and locate cacao climate regions in Arauca. We also present a presence-only matrix consisting of twenty-six tree species, or agrobiodiversity, distributed across the study region and specifically associated with the cacao forestry systems in Arauca. New information: We present the first database of both climate and agrobiodiversity data related to cacao farms in Arauca, developed with a research and socioeconomic vision that generated a novel approach for the agroclimatic zoning of cocoa in the Arauca Region and Colombia. Using 1,538 cacao farms at the regional scale, we identified two national and six regional-scale climate and soil regions. The selection at the local scale allowed us to classify 180 cacao farms comprising nine agroclimatic clusters in Arauca. We found twenty-six tree species distributed across the cacao climate zones. This dataset and its related maps also represent the agrobiodiversity of cultivated cacao locally. This is the most complete climate and agrobiodiversity dataset of cacao farms distribution in one of the top cocoa-producing regions in the country. These outputs are crucial because they constitute a baseline for developing research in the biodiversity of agroforestry systems, pests and diseases, pollutant presence, genetics, post-harvest processing and cocoa quality and safety.

A novel, label-free, pre-equilibrium assay to determine the association and dissociation rate constants of therapeutic antibodies on living cells.

BACKGROUND AND PURPOSE: Monoclonal antibodies (Ab) represent the fastest growing drug class. Knowledge of the biophysical parameters (kon , koff and KD ) that dictate Ab:receptor interaction is critical during the drug discovery process. However, with the increasing complexity of Ab formats and their targets, it became apparent that existing technologies present limitations and are not always suitable to determine these parameters. Therefore, novel affinity determination methods represent an unmet assay need. EXPERIMENTAL APPROACH: We developed a pre-equilibrium kinetic exclusion assay using recent mathematical advances to determine the kon , koff and KD of monoclonal Ab:receptor interactions on living cells. The assay is amenable to all human IgG1 and rabbit Abs. KEY RESULTS: Using our novel assay, we demonstrated for several monoclonal Ab:receptor pairs that the calculated kinetic rate constants were comparable with orthogonal methods that were lower throughput or more resource consuming. We ran simulations to predict the critical conditions to improve the performance of the assays. We further showed that this method could successfully be applied to both suspension and adherent cells. Finally, we demonstrated that kon and koff , but not KD , correlate with in vitro potency for a panel of monoclonal Abs. CONCLUSIONS AND IMPLICATIONS: Our novel assay has the potential to systematically probe binding kinetics of monoclonal Abs to cells and can be incorporated in a screening cascade to identify new therapeutic candidates. Wide-spread adoption of pre-equilibrium assays using physiologically relevant systems will lead to a more holistic understanding of how Ab binding kinetics influence their potency.

The Association between Pesticide Exposure and the Development of Fronto-Temporal Dementia-Cum-Dissociative Disorders: A Review.

Pesticides are chemicals used in agricultural fields for the prevention or destruction of pests. Inappropriate use of these substances, as well as handling them without using personal protective equipment, may result in serious health problems such as neurodegenerative diseases and mental disorders. Previous studies have demonstrated the adverse effects of pesticides on brain function. However, some researchers have associated pesticide poisoning with the development of disorders such as dissociative amnesia, multiple personality disorders, and depersonalization disorder. The objective of this work was to perform a bibliographic review of the relationship between pesticide poisoning and the development of dissociative disorders. Previous studies suggest that the duration of pesticide exposure is a major determinant in the development of dissociative diseases and disorders. The information obtained in this review suggests that there is no specific relationship between dissociative disorders and pesticide poisoning. However, these results point to associating the most representative symptoms of dissociative disorder (such as amnesia and memory loss) with pesticide exposure. Based on the bibliographic search, possible mechanisms of action were suggested in an attempt to explain a possible association between exposure to pesticides and the appearance of dissociative disorders.

Staphylococcus aureus in the Processing Environment of Cured Meat Products.

The presence of Staphylococcus aureus in six dry-cured meat-processing facilities was investigated. S. aureus was detected in 3.8% of surfaces from five facilities. The occurrence was clearly higher during processing (4.8%) than after cleaning and disinfection (1.4%). Thirty-eight isolates were typified by PFGE and MLST. Eleven sequence types (STs) were defined by MLST. ST30 (32%) and ST12 (24%) were the most abundant. Enterotoxin genes were detected in 53% of isolates. The enterotoxin A gene (sea) was present in all ST30 isolates, seb in one ST1 isolate, and sec in two ST45 isolates. Sixteen isolates harbored the enterotoxin gene cluster (egc) with four variations in the sequence. The toxic shock syndrome toxin gene (tst) was detected in 82% of isolates. Regarding antimicrobial resistance, twelve strains were susceptible to all the antibiotics tested (31.6%). However, 15.8% were resistant to three or more antimicrobials and, therefore, multidrug-resistant. Our results showed that in general, efficient cleaning and disinfection procedures were applied. Nonetheless, the presence of S. aureus with virulence determinants and resistance to antimicrobials, particularly multidrug-resistant MRSA ST398 strains, might represent a potential health hazard for consumers.

A Real-Time Image-Based Efferocytosis Assay for the Discovery of Functionally Inhibitory Anti-MerTK Antibodies.

Efferocytosis is a phagocytic process by which apoptotic cells are cleared by professional and nonprofessional phagocytic cells. In tumors, efferocytosis of apoptotic cancer cells by tumor-associated macrophages prevents Ag presentation and suppresses the host immune response against the tumor. Therefore, reactivating the immune response by blockade of tumor-associated macrophage-mediated efferocytosis is an attractive strategy for cancer immunotherapy. Even though several methods have been developed to monitor efferocytosis, an automated and high-throughput quantitative assay should offer highly desirable advantages for drug discovery. In this study, we describe a real-time efferocytosis assay with an imaging system for live-cell analysis. Using this assay, we successfully discovered potent anti-MerTK Abs that block tumor-associated macrophage-mediated efferocytosis in mice. Furthermore, we used primary human and cynomolgus monkey macrophages to identify and characterize anti-MerTK Abs for potential clinical development. By studying the phagocytic activities of different types of macrophages, we demonstrated that our efferocytosis assay is robust for screening and characterization of drug candidates that inhibit unwanted efferocytosis. Moreover, our assay is also applicable to investigating the kinetics and molecular mechanisms of efferocytosis/phagocytosis.

CT-based pathological lung opacities volume as a predictor of critical illness and inflammatory response severity in patients with COVID-19.

Objective: The aim of the study was to assess the impact of CT-based lung pathological opacities volume on critical illness and inflammatory response severity of patients with COVID-19. Methods: A retrospective, single center, single arm study was performed over a 30-day period. In total, 138 patients (85.2%) met inclusion criteria. All patients were evaluated with non-contrast enhanced chest CT scan at hospital admission. CT-based lung segmentation was performed to calculate pathological lung opacities volume (LOV). At baseline, complete blood count (CBC) and inflammation response biomarkers were obtained. The primary endpoint of the study was the occurrence of critical illness, as defined as, the need of mechanical ventilation and/or ICU admission. Mann-Whitney U test was performed for univariate analysis. Logistic regression analysis was performed to determine independent predictors of critical illness. Spearman analysis was performed to assess the correlation between inflammatory response biomarkers serum concentrations and LOV. Results: Median LOV was 28.64% (interquartile range [IQR], 6.33-47.22%). Correlation analysis demonstrated that LOV was correlated with higher levels of D-dimer (r = 0.51, p < 0.01), procalcitonin (r = 0.47, p < 0.01) and IL6 (r = 0.48, p < 0.01). Critical illness occurred in 51 patients (37%). Univariate analysis demonstrated that inflammatory response biomarkers and LOV were associated with critical illness (p < 0.05). However, multivariate analysis demonstrated that only D-dimer and LOV were independent predictors of critical illness. Furthermore, a ROC analysis demonstrated that a LOV equal or greater than 60% had a sensitivity of 82.1% and specificity of 70.2% to determine critical illness with an odds ratio of 19.4 (95% CI, 4.2-88.9). Conclusion: Critical illness may occur in up to 37% of the patients with COVID-19. Among patients with critical illness, higher levels of inflammatory response biomarkers with larger LOVs were observed. Furthermore, multivariate analysis demonstrated that pathological lung opacities volume was an independent predictor of critical illness. In fact, patients with a pathological lung opacities volume equal or greater than 60% had 19.4-fold increased risk of critical illness.

PEGylation of anti-MerTK Antibody Modulates Ocular Biodistribution.

Here, we explore whether PEGylation of antibodies can modulate their biodistribution to the eye, an organ once thought to be immune privileged but has recently been shown to be accessible to IV-administered large molecules, such as antibodies. We chose to PEGylate an anti-MerTK antibody, a target with known potential for ocular toxicity, to minimize biodistribution to retinal pigment epithelial cells (RPEs) in the eye by increasing the hydrodynamic volume of the antibody. We used site-specific conjugation to an engineered cysteine on anti-MerTK antibody to chemically attach 40-kDa branched or linear PEG polymers. Despite reduced binding to MerTK on cells, site-specifically PEGylated anti-MerTK retained similar potency in inhibiting MerTK-mediated macrophage efferocytosis of apoptotic cells. Importantly, we found that PEGylation of anti-MerTK significantly reduced MerTK receptor occupancy in RPE cells in both naïve mice and MC-38 tumor-bearing mice, with the branched PEG exhibiting a greater effect than linear PEG. Furthermore, similar to unconjugated anti-MerTK, PEGylated anti-MerTK antibody triggered type I IFN response and exhibited antitumor effect in syngeneic mouse tumor studies. Our results demonstrate the potential of PEGylation to control ocular biodistribution of antibodies.

Habitat manipulation for sustainable management of Philaenus spumarius, the main vector of Xylella fastidiosa in Europe.

BACKGROUND: The unexpected Xylella fastidiosa (Xf) outbreak in Europe has led to aggressive management of the disease in recent years. As there is no cure for infected plants, management of vector populations is mandatory to contain the spread of Xf in infected areas. We aimed to assess the suitability of plant species commonly used as cover crops for the population growth of Philaenus spumarius L. (Aphrophoridae). Thus, we conducted a series of no-choice and multiple-choice assays to assess the oviposition preference of P. spumarius adults as well as the development and mortality rate of nymphs on 10 candidate plant species under laboratory and semi-field conditions. Our results will help to design ecological infrastructures, including a pull-push strategy for effective management of Xf vectors in olive groves. RESULTS: Results showed that Anthriscus cerefolium is a suitable plant to enhance oviposition but has a lethal effect on the first nymphal instars of P. spumarius. Moreover, Diplotaxis tenuifolia is not suitable for oviposition or nymphal development. Sinapis alba does not enhance oviposition but is suitable for nymphal development with a medium-high cumulative mortality of the nymphs. Conversely, adults and nymphs had a high preference and low mortality on Taraxacum officinale, and nymphs showed a medium-high preference on Lavandula angustifolia, suggesting that these two species should be avoided as ground cover plants on Xf-susceptible crops. CONCLUSION: The results obtained in our study open new ways to manage the vectors of Xf by using specific plant species as ground cover, which in turn will reduce the spread and prevalence of Xf. © 2022 Society of Chemical Industry.

[Differences among renin-angiotensin system inhibitor drugs in prognosis of hypertense patients with COVID-19]. / Diferencias entre fármacos inhibidores del sistema renina-angiotensina en pacientes hipertensos ingresados por COVID-19.

Introduction: Concerns have been raised about Renin-angiotensin system inhibitors (RASi) in patients with COVID-19. Although recent trials have proved its security, evidence regarding intrinsic differences between RASi is lacking, especially in patients with arterial hypertension. Our objective was to analyse the prognosis of hypertense patients who received angiotensin converting enzyme inhibitors (ACEi) or angiotensin-2 receptor blockers (ARBs) and were hospitalized due to COVID-19. Materials and methods: 392 consecutive patients with hypertension and COVID-19 were analyse. Incidence of the combined event (death or mechanical ventilation need) was the primary endpoint. Secondary, incidence of each event and time to event were analysed. Results: 155 received ACEi and 237 ARBs. During the hospitalization, the combined event was observed in the 31,6 % of patients. No differences were observed between those previously treated with ACEi and ARBs (33.5 vs. 30.9%; p = 0.51). In the survival analysis, no differences were observed regarding time to combined event (p = 0.91). In-hospital mortality was similar in both groups (32.3 vs. 29.1%; p = 0.51), as well as the need of mechanical ventilation (3.2 vs. 5.9%; p = 0.23). Conclusions: The type of RASi was not associated with in-hospital major events in patients with arterial hypertension hospitalized due to COVID-19.

Introducción: Han surgido dudas sobre la seguridad de los fármacos inhibidores del sistema renina-angiotensina (SRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19). Aunque estudios recientes han demostrado la seguridad de este grupo de fármacos, la evidencia sobre la comparativa de los diferentes fármacos inhibidores del SRA es escasa, sobre todo en pacientes hipertensos. Nuestro objetivo fue analizar el pronóstico de los pacientes hipertensos tratados con inhibidores de la enzima convertidora de angiotensina (IECA) o antagonistas del receptor de angiotensina II (ARA II) que presentaron COVID-19. Materiales y métodos: Se analizaron 582 pacientes hipertensos con COVID-19. Se registró la incidencia del evento combinado de muerte o necesidad de ventilación mecánica invasiva (VMI) durante la hospitalización. De forma secundaria, se analizó la incidencia de eventos de manera independiente y se realizó un análisis de supervivencia para analizar el tiempo hasta los eventos. Resultados: 155 pacientes recibían tratamiento previo con IECA y 237 con ARA II. Durante la hospitalización por COVID-19, se observó una incidencia del evento combinado del 31.6%. No se detectaron diferencias entre los pacientes que recibían tratamiento con IECA y los tratados con ARA II (33.5 vs. 30.9%; p = 0.51). En el análisis de supervivencia, no se hallaron diferencias en el tiempo hasta el evento combinado (p = 0.91). La mortalidad intrahospitalaria fue similar en ambos grupos (32.3 vs. 29.1%; p = 0.51), así como la necesidad de VMI (3.2 vs. 5.9%; p = 0.23). Conclusiones: El tipo de inhibidor del SRA no se asoció a diferencias pronósticas significativas entre los pacientes hipertensos ingresados con COVID-19.

'From soil to chocolate bar': identifying critical steps in the journey of cadmium in a Colombian cacao plantation.

Regulation of maximum levels of cadmium in chocolate is an issue for cacao exportation from many parts of Latin America, including Colombia. These limits are related to the final product, but buyers often request maximum levels of Cd in the beans. However, to date, there is neither a clear understanding of the relationship between the specified levels of Cd in chocolate and cocoa derivatives and levels in harvested beans or soil nor of the effect of post-harvest processes on the levels of Cd in the final product. To address this, the fate of Cd concentration from soil to chocolate bar was followed in a single farm in Santander district, Colombia. The concentration of Cd in soils was measured using ICP-OES and correlated with soil pH, soil organic matter (SOM), and the use of P-based fertilisers. Cd concentrations were also measured in unfermented seeds, fermented and dried beans, shell, nibs, and chocolate. SOM (2.93-3.78%), soil pH (4.7-4.9), soil P concentration (120-132 mg kg-1) affect Cd availability. However, it is still unclear whether Cd concentration of P-based fertilisers (3-30 mg kg-1) is important or not. While post-harvest treatments did not affect the Cd concentration of beans (4.17 ± 0.8 mg kg-1 on average), the removal of the shell (6.57 mg kg-1) from the nibs (3.28 mg kg-1), as well as the percentage of cocoa mass used contributes to a reduction in Cd concentration in the chocolate bar (1.60 mg kg-1). This study provides clear indications on where research into mitigation measures should be focussed, as well as indicating the importance of carrying out analyses for Cd in the nib or cacao mass, rather than the whole bean, reducing Cd concentration by up to 40%.

Genetic profile for the detection of susceptibility to poisoning by exposure to pesticides.

INTRODUCTION: In humans, there are sets of genes that encode enzymes that decrease or increase the risks derived from exposure to pesticides. These include DNA repair genes (XRCC1, OGG1 and XRCC4); pesticide metabolizers (GSTP1 and PON1), and genes that act against oxidative stress (SOD2 and NQO1). OBJECTIVE: The aim of this literature review is to provide information about the genes involved in the defence systems against exposure to pesticides, as well as their polymorphisms, functions, and general characteristics of the encoded enzymes. MATERIAL AND METHODS: Information was obtained from scientific articles published between 2015-2020 in the PubMed database (https://pubmed.ncbi.nlm.nih.gov). RESULTS: Genes related to the defence processes against pesticides present single-nucleotide polymorphisms (SNPs) with allelic variants that affect the expressions or structures of the encoded enzymes, negatively altering their activities. If we knew the genetic profile that includes polymorphisms of DNA-repairing genes, metabolizing genes, and genes against oxidative stress in subjects exposed to pesticides, we would also know about their susceptibility to poisoning caused by these chemicals. CONCLUSIONS: The genes could be used to propose a genetic profile in farmers exposed to various pesticides, including 10 gene polymorphisms involved in susceptibility to various pathologies related to DNA repair, xenobiotic metabolism, and oxidative stress. It could also be useful as a preventive measure to identify susceptibility to pesticide poisoning.

Computed Tomography-based Lung Residual Volume and Mortality of Patients With Coronavirus Disease-19 (COVID-19).

RATIONALE AND OBJECTIVES: To assess the effect of computed tomography (CT)-based residual lung volume (RLV) on mortality of patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: A single-center, retrospective study of a prospectively maintained database was performed. In total, 138 patients with COVID-19 were enrolled. Baseline chest CT scan was performed in all patients. CT-based automated and semi-automated lung segmentation was performed using the Alma Medical workstation to calculate normal lung volume, lung opacities volume, total lung volume, and RLV. The primary end point of the study was mortality. Univariate and multivariate analyses were performed to determine independent predictors of mortality. RESULTS: Overall, 84 men (61%) and 54 women (39%) with a mean age of 47.3 years (±14.3 y) were included in the study. Overall mortality rate was 21% (29 patients) at a median time of 7 days (interquartile range, 4 to 11 d). Univariate analysis demonstrated that age, hypertension, and diabetes were associated with death (P<0.01). Similarly, patients who died had lower normal lung volume and RLV than patients who survived (P<0.01). Multivariate analysis demonstrated that low RLV was the only independent predictor of death (odds ratio, 1.042; 95% confidence interval, 10.2-10.65). Furthermore, receiver operating characteristic curve analysis demonstrated that a RLV ≤64% significantly increased the risk of death (odds ratio, 4.8; 95% confidence interval, 1.9-11.7). CONCLUSION: Overall mortality of patients with COVID-19 may reach 21%. Univariate and multivariate analyses demonstrated that reduced RLV was the principal independent predictor of death. Furthermore, RLV ≤64% is associated with a 4-fold increase on the risk of death.

A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment.

Despite the development of effective therapies, a substantial proportion of asthmatics continue to have uncontrolled symptoms, airflow limitation, and exacerbations. Transient receptor potential cation channel member A1 (TRPA1) agonists are elevated in human asthmatic airways, and in rodents, TRPA1 is involved in the induction of airway inflammation and hyperreactivity. Here, the discovery and early clinical development of GDC-0334, a highly potent, selective, and orally bioavailable TRPA1 antagonist, is described. GDC-0334 inhibited TRPA1 function on airway smooth muscle and sensory neurons, decreasing edema, dermal blood flow (DBF), cough, and allergic airway inflammation in several preclinical species. In a healthy volunteer Phase 1 study, treatment with GDC-0334 reduced TRPA1 agonist-induced DBF, pain, and itch, demonstrating GDC-0334 target engagement in humans. These data provide therapeutic rationale for evaluating TRPA1 inhibition as a clinical therapy for asthma.

Análisis de la relación entre los inhibidores del sistema renina-angiotensina y la evolución de pacientes hospitalizados por infección respiratoria COVID-19 / Comparative analysis between the use of renin-angiotensin system antagonists and clinical outcomes of hospitalized patients with COVID-19 respiratory infection

INTRODUCCIÓN: La presencia de hipertensión arterial se asocia con peor pronóstico en pacientes con COVID-19, y se ha sugerido que el uso de inhibidores del eje renina-angiotensina puede influir en el pronóstico de los pacientes. MÉTODOS: Registro observacional de 921 pacientes consecutivos ingresados por infección respiratoria COVID-19 entre el 1 de marzo y el 30 abril de 2020 en el Hospital General Universitario de Ciudad Real. Se registraron datos clínicos y analíticos, intervenciones terapéuticas y desarrollo de eventos durante el ingreso hospitalario. RESULTADOS: La mediana de edad fue de 78 años y el 59,2% tenían hipertensión arterial. Aunque el perfil clínico fue más desfavorable en el grupo de pacientes con prescripción previa de IECA o ARA2 respecto al resto, los primeros presentaron menor riesgo de desarrollo del evento primario combinado (mortalidad total o necesidad de soporte ventilatorio invasivo). Asimismo, el empleo previo al ingreso o durante el mismo de estos fármacos mostró un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva. En el análisis de supervivencia no se observó mayor riesgo de presentar más precozmente ninguno de los eventos registrados. CONCLUSIONES: La prescripción previa al ingreso por infección respiratoria COVID-19 de inhibidores del eje renina-angiotensina se asoció a un menor riesgo de desarrollo del evento primario combinado y a un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva

INTRODUCTION: Hypertension has been associated with worse outcomes in patients with COVID-19 infection, so concerns have been raised about the possibility that inhibitors of the renin-angiotensin system (RAS) could influence the prognosis of these patients. METHODS: This is an observational study of 921 consecutive patients admitted with COVID-19 respiratory infection to Hospital General Universitario Ciudad Real from March 1 to April 30, 2020. Following data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions during the hospitalization and clinical outcomes. RESULTS: The mean age was 78 years, and 59.2% of patients had a history of hypertension. Patients with previous treatment with RAS inhibitor (42.4%) showed lower risk of the primary composite endpoint (mortality or need for invasive mechanical ventilation). Treatment with RAS inhibitor (both outpatient treatment and during hospitalization) had neither effect on mortality nor need for invasive ventilation. There were no differences in time-to-event analysis between groups. CONCLUSIONS: RAS inhibitor treatment prior to admission in patients with COVID-19 respiratory infection was associated with lower risk of the primary composite endpoint and did not show neither impact on mortality nor need for invasive mechanical ventilation, even if these drugs were prescribed during hospitalization

Comparative analysis between the use of renin-angiotensin system antagonists and clinical outcomes of hospitalized patients with COVID-19 respiratory infection.

INTRODUCTION: Hypertension has been associated with worse outcomes in patients with COVID-19 infection, so concerns have been raised about the possibility that inhibitors of the renin-angiotensin system (RAS) could influence the prognosis of these patients. METHODS: This is an observational study of 921 consecutive patients admitted with COVID-19 respiratory infection to Hospital General Universitario Ciudad Real from March 1 to April 30, 2020. Following data were collected including patient demographic information, medical history, clinical characteristics, laboratory data, therapeutic interventions during the hospitalization and clinical outcomes. RESULTS: The mean age was 78 years, and 59.2% of patients had a history of hypertension. Patients with previous treatment with RAS inhibitor (42.4%) showed lower risk of the primary composite endpoint (mortality or need for invasive mechanical ventilation). Treatment with RAS inhibitor (both outpatient treatment and during hospitalization) had neither effect on mortality nor need for invasive ventilation. There were no differences in time-to-event analysis between groups. CONCLUSIONS: RAS inhibitor treatment prior to admission in patients with COVID-19 respiratory infection was associated with lower risk of the primary composite endpoint and did not show neither impact on mortality nor need for invasive mechanical ventilation, even if these drugs were prescribed during hospitalization.

INTRODUCCIÓN: La presencia de hipertensión arterial se asocia con peor pronóstico en pacientes con COVID-19, y se ha sugerido que el uso de inhibidores del eje renina-angiotensina puede influir en el pronóstico de los pacientes. MÉTODOS: Registro observacional de 921 pacientes consecutivos ingresados por infección respiratoria COVID-19 entre el 1 de marzo y el 30 abril de 2020 en el Hospital General Universitario de Ciudad Real. Se registraron datos clínicos y analíticos, intervenciones terapéuticas y desarrollo de eventos durante el ingreso hospitalario. RESULTADOS: La mediana de edad fue de 78 años y el 59,2% tenían hipertensión arterial. Aunque el perfil clínico fue más desfavorable en el grupo de pacientes con prescripción previa de IECA o ARA2 respecto al resto, los primeros presentaron menor riesgo de desarrollo del evento primario combinado (mortalidad total o necesidad de soporte ventilatorio invasivo). Asimismo, el empleo previo al ingreso o durante el mismo de estos fármacos mostró un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva. En el análisis de supervivencia no se observó mayor riesgo de presentar más precozmente ninguno de los eventos registrados. CONCLUSIONES: La prescripción previa al ingreso por infección respiratoria COVID-19 de inhibidores del eje renina-angiotensina se asoció a un menor riesgo de desarrollo del evento primario combinado y a un efecto neutro sobre la mortalidad total y sobre la necesidad de ventilación mecánica invasiva.

Impact of Treatment with Renin-Angiotensin System Inhibitors on Clinical Outcomes in Hypertensive Patients Hospitalized with COVID-19.

INTRODUCTION: Concerns have been raised about the possible harmfulness of angiotensin-converter enzyme inhibitors (ACEi) and aldosterone receptor blockers (ARB) in patients with COVID-19. However, few data from a European population have been published, especially from hypertensive patients. AIM: To study the association between ACEi or ARB treatments and major adverse outcomes during hospitalisation in COVID-19 patients. METHODS: We studied 545 consecutive hypertensive patients admitted to our institution due to COVID-19 with respiratory involvement. We analysed the incidence of combined event (death or mechanical ventilatory support) during hospitalisation, as well as the time to independent events. RESULTS: 188 (34.5%) patients presented the combined endpoint. 182 (33.4%) patients died, and 21 (3.9%) needed mechanical ventilatory support. Patients with previous treatment with ACEi or ARB presented similar incidence of the combined endpoint during hospitalisation (31.6% vs. 41.8%; p = 0.08), with a lower all-cause mortality rate (30.4% vs. 41.2%; p = 0.03) compared with those without prior treatment. Use of ACEi or ARB was not independently associated with lower incidence of the combined endpoint [Adjusted OR 0.675 (95% CI 0.298-1.528; p = 0.146)], but it was associated with lower mortality [Adjusted OR 0.550 (95% CI 0.304-0.930; p = 0.047)]. CONCLUSIONS: The use of ACEi or ARB was associated with less incidence of all-cause death during hospitalisation among hypertensive patients admitted with COVID-19 respiratory infection.