A temporal analysis of the consequences of the drought regime on the water footprint of agriculture in the Guadalupe Valley, Mexico.

Changes in water availability have a substantial impact on the sustainability and maintenance of agriculture, with water footprint (WF) being a robust methodology to assess these transformations. The Guadalupe Valley is one of the places with the highest agricultural production in Mexico. Despite its semi-arid climatic conditions, it provides high-quality crops that are well-positioned in the world. The historical trend of rainfall and temperatures between 1987 and 2017 was analyzed to identify climatic patterns in the territory. Through the calculations of the water footprint of Grapevine and Olive crops, the sensitivity of the crops to recurrent water deficit and their adaptation in their yields to drought episodes was identified. The reduction in precipitation and occurrence of extreme temperatures have contributed significantly towards augmenting crop evapotranspiration and, consequently, intensifying crop irrigation demands. As a result, there has been an apparent increase in the consumption of WFagricultural since 2007. Thus, the period of highest WFagricultural consumption was 2014 (Extremely dry), as opposed to 2011 (Very wet). In particular, the lowest WFgreen consumptions were observed in extremely dry years, that is, > 20% of the WFagricultural intensifying drought events. Therefore, these periods were compensated with higher uses of WFblue and WFgray, which are inversely correlated with precipitation, where vine crops consume 73% more WFagricultural compared to olive plantations, showing greater interannual variability. These results contribute to analyzing the temporal evolution of water consumption for agriculture, providing a basis for rational water use strategies.

Chronic Undernutrition in Ovine Twin Pregnancies Abolishes Differences in Birth Weight Due to Sex: An Evaluation of the Role of Nutritional and Antioxidant Supplementation.

In twin pregnancies of discordant sex, the male fetus grows larger than the female co-twin. Our study aimed to determine the effect of the sex of co-twins on lambs' birth weight in ovine pregnancies developed under natural undernourishment. Additionally, we investigated whether the nutritional and/or antioxidant supplementation provided to ewes during pregnancy could modulate the potential effects associated with the sex of co-twins. Ninety-six birth records of twin pregnancies of sheep grazing the natural Patagonian prairies were analyzed. The animals were divided into four groups: control (no supplementation), N (concentrate supplementation, 100% NRC), A (antioxidant supplementation), and NA (concentrate + antioxidant supplementation). Supplementation occurred from day 35 of gestation onwards until lambing. There were no differences in female or male birth weight in the control undernourished group. However, in group N, females or males with sex-discordant co-twins had a higher birth weight than did those with co-twins of the same sex. Group A males with female co-twins had a higher birth weight compared to males whose co-twins were also males. In NA lambs, males had a higher birth weight compared to females, regardless of their co-twin's sex. Therefore, chronic undernutrition abolished the differences in birth weight due to fetal sex. Restoring maternal nutrition or antioxidant supplementation tends to normalize birth weight and restore the differences between females and males. This effect is enhanced with the combined supplementation of concentrated food and antioxidants.

Analysis of drug of abuse compounds using passive sampling and ultrahigh-liquid chromatography coupled to mass spectrometry.

The present study proposes the monitoring of compounds of drugs of abuse through the use of passive samplers in water systems. Initially, four positive ion compounds of interest were determined according to national surveys, and then composite sampling and passive sampling were implemented using continuous-flow passive samplers containing two types of sorbents, the Empore disk and Gerstel Twister. Two study sites were established at the beginning and at the end of the middle Bogotá River basin. After 4 days, the sorbents were removed so that they could be desorbed and analyzed using UHPLC-MS in the laboratory. For the composite samples, the results were below the first calibration curve point (FCCP) of the chromatographic method, and for passive sampling, peaks of benzoylecgonine (BE) (21427.3 pg mL-1), methamphetamine (MET) (67101.5 pg mL-1), MDMA (ecstasy) (225844.8 pg mL-1) and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) (15908.4 pg mL-1) were found. Therefore, passive sampling could be suggested as an alternative to composite sampling for the monitoring of compounds.

Human Health Risk Assessment of Arsenic and Other Metals in Herbal Products Containing St. John's Wort in the Metropolitan Area of Mexico City.

Consumption of St. John's wort plant is high worldwide due to its various medicinal properties. However, herbal products containing St. John's wort may be contaminated with toxic metals. This is often related to contamination of both water and the atmosphere, lack of proper cultivation methods, and inadequate plant storage conditions, as well as a lack of stricter sanitary supervision. A safety assessment of copper (Cu), lead (Pb), cadmium (Cd) and arsenic (As) content in 23 products containing St. John's wort (pharmaceutical herbal products, food supplements and traditional herbal remedies) sold in the metropolitan area of Mexico City was conducted. The analysis of metals was determined using a graphite-furnace atomic absorption spectrometer. All herbal products were contaminated with Cu, Pb, Cd and As. The pharmaceutical herbal items showed less contamination by metals. The daily human intake (DHI) values for Pb exceeded the permissible limits in the group of traditional herbal remedies. The DHI calculation for As exceeded the permitted intake values for all items in the group of traditional herbal remedies, five food supplements and one pharmaceutical herbal product. The hazard indicator calculation of the non-carcinogenic cumulative risk values for traditional herbal remedies was greater than 1, suggesting a risk to human health.

Extracellular Vesicles from Immune Cells: A Biomedical Perspective.

Research on the role of extracellular vesicles (sEV) in physiology has demonstrated their undoubted importance in processes such as the transportation of molecules with significance for cell metabolism, cell communication, and the regulation of mechanisms such as cell differentiation, inflammation, and immunity. Although the role of EVs in the immune response is actively investigated, there is little literature revising, in a comprehensive manner, the role of small EVs produced by immune cells. Here, we present a review of studies reporting the release of sEV by different types of leukocytes and the implications of such observations on cellular homeostasis. We also discuss the function of immune cell-derived sEV and their relationship with pathological states, highlighting their potential application in the biomedical field.

Cardiac copper content and its relationship with heart physiology: Insights based on quantitative genetic and functional analyses using BXD family mice.

Background: Copper (Cu) is essential for the functioning of various enzymes involved in important cellular and physiological processes. Although critical for normal cardiac function, excessive accumulation, or deficiency of Cu in the myocardium is detrimental to the heart. Fluctuations in cardiac Cu content have been shown to cause cardiac pathologies and imbalance in systemic Cu metabolism. However, the genetic basis underlying cardiac Cu levels and their effects on heart traits remain to be understood. Representing the largest murine genetic reference population, BXD strains have been widely used to explore genotype-phenotype associations and identify quantitative trait loci (QTL) and candidate genes. Methods: Cardiac Cu concentration and heart function in BXD strains were measured, followed by QTL mapping. The candidate genes modulating Cu homeostasis in mice hearts were identified using a multi-criteria scoring/filtering approach. Results: Significant correlations were identified between cardiac Cu concentration and left ventricular (LV) internal diameter and volumes at end-diastole and end-systole, demonstrating that the BXDs with higher cardiac Cu levels have larger LV chamber. Conversely, cardiac Cu levels negatively correlated with LV posterior wall thickness, suggesting that lower Cu concentration in the heart is associated with LV hypertrophy. Genetic mapping identified six QTLs containing a total of 217 genes, which were further narrowed down to 21 genes that showed a significant association with cardiac Cu content in mice. Among those, Prex1 and Irx3 are the strongest candidates involved in cardiac Cu modulation. Conclusion: Cardiac Cu level is significantly correlated with heart chamber size and hypertrophy phenotypes in BXD mice, while being regulated by multiple genes in several QTLs. Prex1 and Irx3 may be involved in modulating Cu metabolism and its downstream effects and warrant further experimental and functional validations.

Water footprint and virtual water flows from the Global South: Foundations for sustainable agriculture in periods of drought.

Freshwater availability has decreased alarmingly worldwide, with agriculture playing a vital role in this trend. The assessment of the agricultural water footprint (WFagricultural) and virtual water flows (VWF) is fundamental not only in local water resources management and protection, but also in our understanding of the synergies between local water consumption and global markets. Thus, the WFagricultural - broken down into its components (blue, green, and gray) - of the leading 21 crops (grouped in fruit, legumes, cereals, and vegetables), grown in four basins with the most significant agricultural activity in central Chile was determined, estimated in two consecutive years 2017-2018. In addition, due to their great importance in exports, VWFs were assessed, establishing connections according to their origins and destinations. The results show that the green and gray water footprints increased significantly in the south-central basins, while blue water consumption increased in the basins of the central zone, reflecting an evident WFagricultural transition in accord with latitude and climate conditions. Furthermore, VWF showed an annual increase of 44 %, in about 116 destinations, with Asia, Europe, and North America being the preferred destinations, with annual variations of VWFblue- gray associated with increases in exports of apples, cherries, grapes, blueberries, and walnuts, market preferences and growing areas. The present study is an initial step toward sustainable agriculture in a commodity exporting country, one that is relevant in the exploitation of virtual water yet faces severe water deficit problems, distribution, and local water policies. Therefore, contributing to encouraging the efficiency and value of water in the process of a new institutional framework.

Mecanismos plasmídicos de resistencia a quinolonas, betalactámicos y colistina en Salmonella enterica. Paraguay 2020-2021

Las bacterias son capaces de desarrollar mecanismos de resistencia a los antimicrobianos, aquellos adquiridos y transmisibles son los más significativos debido al potencial de diseminación. La aparición de Salmonella enterica con resistencia a C3aG, quinolonas y a colistina representa una amenaza progresiva. El objetivo fue determinar la resistencia a los antimicrobianos y la presencia de los mecanismos de resistencia plasmídicos a quinolonas, ß-lactámicos y colistina en aislados de Salmonella provenientes de la vigilancia integrada de enteropatógenos. Fueron estudiadas 501 cepas de Salmonella spp. colectadas entre los años 2020 y 2021, por la red de enteropatógenos del Laboratorio Central de Salud Pública. Se investigó la resistencia a las C3aG, quinolonas y colistina, en aislamientos de humanos, alimentos, animales de consumo y ambiente. Las cepas estudiadas exhibieron resistencia a tetraciclina (32,5%), ácido nalidíxico (29%), ampicilina (13,2%), nitrofurantoína (11,6%), C3aG (7,2%), cotrimoxazol (5,8%), ciprofloxacina (2,2%). El 18% (90/501) presentaron resistencia trasferible por plásmidos, fueron detectados 111 genes (71 cepas con un gen, 17 cepas dos genes y 2 cepas tres genes diferentes). Qnr B: 41,1% (37/90), mcr-1: 38,9% (35/90), CMY: 23,3% (21/90), CTX-M: 16,7% (15/90) y Qnr S: 3,3% (3/90). Heidelberg fue el serovar predominante en muestras de pollo y el mayor portador de genes de resistencia de tipo CMY y mcr-1. La detección de genes en alimentos y animales de consumo, que pueden transmitirse fácilmente al ser humano es motivo de alerta y resalta la importancia de continuar fortaleciendo la vigilancia multisectorial y multidisciplinaria.

Bacteria can develop antimicrobial resistance mechanisms, those acquired and transmissible being the most significant due to the potential for dissemination. The emergence of Salmonella enterica with resistance to third-generation cephalosporins, quinolones, and colistin represents a progressive threat. The objective was to determine antimicrobial resistance and the presence of plasmid resistance mechanisms to quinolones, ß-lactams, and colistin in Salmonella isolates from integrated surveillance of enteropathogens. Five hundred and one strains of Salmonella spp. collected between 2020 and 2021 were studied by the enteropathogen network of the Laboratorio Central de Salud Publica (Central Public Health Laboratory). Research was conducted on the resistance to third-generation cephalosporins, quinolones, and colistin, isolated from humans, foodstuffs, animals for consumption, and the environment. The strains studied exhibited resistance to tetracycline (32.5%), nalidixic acid (29%), ampicillin (13.2%), nitrofurantoin (11.6%), third-generation cephalosporins (7.2%), cotrimoxazole (5.8%), and ciprofloxacin (2.2%). Eighteen percent (90/501) presented plasmid-transferable resistance, 111 genes were detected (71 strains with one gene, 17 strains with two genes, and 2 strains with three different genes). Qnr B: 41.1% (37/90), mcr-1: 38.9% (35/90), CMY: 23.3% (21/90), CTX-M: 16.7% (15/90), and Qnr S: 3.3% (3/90). Heidelberg was the predominant serovar in chicken samples and the largest carrier of CMY and mcr-1 resistance genes. The detection of genes in foodstuffs and animals for consumption, which can be easily transmitted to humans, is a cause for alarm and highlights the importance of continuing to strengthen multisectoral and multidisciplinary surveillance.

Historical Aspects of Herbal Use and Comparison of Current Regulations of Herbal Products between Mexico, Canada and the United States of America.

Increased life expectancy and high costs of medicines and medical care have led to the use of herbal products. However, these items may contain toxic compounds that have an impact on public health. We will focus on the regulatory aspects and differences of these products marketed in the North American region (USA-Mexico-Canada) from government websites and selected literature. Mexico has an ancestral tradition of using plants for the treatment, improvement, and maintenance of human health as compared with Canada and the USA Currently, the use of herbal products in this region has a regulatory framework. The legal framework in these three countries is related to their history, idiosyncrasies, socio-economic and cultural aspects. Therefore, there are different public policies for herbal products consumed in the region. Mexico has a more specific classification of these products. In Canada, all herbal products are classified as natural health products and the safety and efficacy must be scientifically proven. In the USA, the development of botanical drugs is very recent. In particular, both herbal products classified as food supplements in Mexico and dietary supplements in the USA may have risks in both safety and efficacy.

Preliminary assessment of antivenom availability and management in the public health system of Costa Rica: An analysis based on a survey to pharmacists in public health facilities.

Availability and accessibility of safe and effective antivenoms are key elements for the successful treatment of snakebite envenoming (SBE). This study provides a preliminary analysis on the way antivenoms are managed by the public health system in Costa Rica and on the role played by pharmacists in the overall management of antivenoms. This was an observational, cross-sectional study based on an online survey sent to pharmacists working at Caja Costarricense de Seguro Social (Costa Rican Social Security System; CCSS) in different locations in Costa Rica. Characteristics and location of health facilities, as well as antivenom availability and management details, were analyzed. Responses from a total of 96 pharmacists, corresponding to 55 different healthcare facilities, were included in this study. Most respondents worked at pharmacies located in urban communities (69.0%) and in the secondary level of care, which includes clinics, and regional and peripheral hospitals (55.2%). Overall, participants reported antivenom availability at all levels of care and in centers having various operating schedules, although they were not available in some facilities in regions where SBE is uncommon or do not attend SBE cases because of the proximity of more complex health centers. On average, the stocks of anticoral and polyvalent antivenoms per health facility were compatible with the dose of antivenom required for treating a SBE case. More than half of participants reported knowing the availability of protocols for the management of SBE and the correct use of antivenom at their healthcare facilities. Of the total respondents, 49% agreed on possessing all the resources needed for the correct management of these medicines at their facilities, and 65.6% indicated that they know the procedures for antivenom storage and management. Our findings provide a first description of the availability of antivenoms in the public health system of Costa Rica, including the primary care level. Results also underscore the perceived role of participating pharmacists in the management of these life-saving drugs and the need to improve their knowledge on this topic.

Occurrence of leaf rust disease in Oxalis triangularis caused by Puccinia oxalidis in Valdivia, Chile.

False shamrock (Oxalis triangularis), native to South America, is an ornamental and popular plant bulb, commercialized for their attractive shape and color (purple triangular leaves) (Taha et al., 2013). In Chile, a rust was detected in O. triangularis plants growing from April to June in several gardens (n=10) in the city of Valdivia, estimating a disease incidence between 80 and 100%. The symptoms appeared as diffuse chlorotic spots from the upperside of leaves, where infected tissues eventually become completely necrotic, and yellow rust pustules were observed on the underside of leaves. Severe symptoms on infected leaves were consistently observed, showing necrosis on entire leaves. Symptomatic plants (n=50) were collected, and three representative isolates from different localities (OX1, OX2, and OX3) were used for morphological and genetic identification. Uredinia (n=20) were hypophyllous, erumpent, yellow, and irregularly distributed, with sizes from 340 to 850 µm in diameter. Urediniospores (n=150) were yellow, subglobose to globose, equinulate, with measures of 14.2 - 17.7 x 14.7 - 17.2 µm. Teliospores were absent. Based on morphological characters, this rust was identified as a Puccinia sp. These morphological characteristics coincided with those indicated by Safránková (2014), Abbasi et al. (2018), and Khouader et al. (2018). To classify this rust genetically, sequences analyses were performed using the ITS region of the rDNA (ITS4/ITS5) (White et al., 1990). The DNA was extracted using a commercial kit. The results indicated 99% similarity with two reference sequences of P. oxalidis (MH325473 and MH325474) available at GenBank (NCBI http://www.ncbi.nlm.nih.gov/BLAST/). The sequences obtained were deposited in GenBank (ON259085 to ON259087). Based on the maximum parsimony phylogenetic tree, the sequences of Chilean isolates were clustered with those of P. oxalidis references. Pathogenicity tests were conducted using three isolates (OX1 to OX3). Surface disinfection of leaves of O. triangularis (n=36 plants), were performed by spraying 1% NaOCl solution for 1 min. Subsequently, 2 mL of urediniospores suspensions of each isolate (OX1 to OX3) at a concentration of 106 urediniospores/mL, were sprayed with an atomizer on the underside of the leaves of all plants. Urediniospores were obtained following the methodology proposed by Ferrada et al. (2020). Control leaves were disinfested and inoculated with sterile distilled water. Plants of O. triangularis of 90-day-old were incubated in a humid chamber (24°C, 80% HR), with a photoperiod of 12 light /12 dark. At 11 days post-inoculation, all leaves inoculated developed chlorosis spots and pulverulent pustules (averaged 10.9 to 25.4 pustules per leaf), and then at 26 days post-inoculation, affected leaves showed necrotic tissues. The identity of these isolates was confirmed morphologically. The symptoms in the control leaves were negative. To our knowledge, this is the first report of multiple occurrences of the leaf rust disease on gardens of false shamrock caused by P. oxalidis in Valdivia, south of Chile. Previously, P. oxalidis has been reported to cause leaf rust disease in O. triangularis in the Czech Republic (Safránková, 2014) and O. debilis in Korea (Lee et al., 2018). The leaf rust disease could represent a threat to the ornamental gardens of O. triangularis in Valdivia. Currently, epidemiological studies of leaf rust disease are necessary to develop management strategies in gardens of O. triangularis.

Short run "rebound effect" of COVID on the transport carbon footprint.

The COVID-19 pandemic completely transformed the mobility of cities. The restrictions on movement led to "empty cities" throughout the world, with some environmental effects in terms of clean air and the reduction of CO2 emissions. This research considers how COVID-19 mobility restrictions have affected the carbon footprint of four medium-sized Chilean cities (Coronel, Temuco, Valdivia, and Osorno) that have environmental problems and are highly dependent on motorized systems. The study uses data from 2400 household surveys at three distinct times: pre-pandemic - T0 (winter 2019), the time of implementation of restrictive mobility policies to contain the pandemic - T1 (winter 2020), and six months later when those restrictions were gradually lifted - T2 (summer 2021). The analysis suggests that CO2 emissions actually went up, declining in the winter 2020, but then increasing with the greater use of cars in the summer 2021 due to the temporary effects of commuting to work, ultimately reaching levels higher than the pre-pandemic values, known as the "rebound effect."

A global horizon scan for urban evolutionary ecology.

Research on the evolutionary ecology of urban areas reveals how human-induced evolutionary changes affect biodiversity and essential ecosystem services. In a rapidly urbanizing world imposing many selective pressures, a time-sensitive goal is to identify the emergent issues and research priorities that affect the ecology and evolution of species within cities. Here, we report the results of a horizon scan of research questions in urban evolutionary ecology submitted by 100 interdisciplinary scholars. We identified 30 top questions organized into six themes that highlight priorities for future research. These research questions will require methodological advances and interdisciplinary collaborations, with continued revision as the field of urban evolutionary ecology expands with the rapid growth of cities.

Vigilancia de la resistencia a los antimicrobianos en cepas de Neisseria gonorrhoeae aisladas en Paraguay. Año 2021

Neisseria gonorrhoeae (N. gonorrhoeae) es el agente causal de la gonorrea, infección de transmisión sexual (ITS) que corresponde a la segunda causa más frecuente de ITS a nivel mundial, provocando una alta morbilidad y costo en atención de salud. En las últimas décadas han aumentado los reportes a nivel mundial de cepas resistentes a penicilina, sulfonamidas, tetraciclina, macrólidos y fluoroquinolonas, y más recientemente a azitromicina y cefalosporinas de espectro extendido como ceftriaxona y cefixima. El objetivo principal de este estudio fue determinar la sensibilidad a los antimicrobianos en cepas de N. gonorrhoeae que fueron enviadas al Laboratorio Central de Salud Pública (LCSP), por los centros colaboradores de la Red de Vigilancia Laboratorial de la Resistencia a los Antimicrobianos (RAM). Para ello, se realizó un estudio prospectivo de corte transversal de enero a diciembre de 2021. Se caracterizaron 128 cepas como N. gonorrhoeae a las cuales se le realizaron pruebas de susceptibilidad obteniéndose 48% de resistencia y 52% de sensibilidad intermedia a penicilina. El 70% presentó resistencia a ciprofloxacina y el 19% a tetraciclina. Se obtuvo 100% de sensibilidad a ceftriaxona y cefixima. El fenotipo de resistencia de mayor prevalencia fue QRNG, asociado con resistencia a ciprofloxacina, seguido del fenotipo PPNG-QRNG, asociado con resistencia a penicilina y ciprofloxacina. Ante estos hallazgos y frente a la emergencia mundial de la resistencia a los antimicrobianos, especialmente de cefalosporinas de espectro extendido, se recomienda que los laboratorios de bacteriología fortalezcan la vigilancia para apoyar la detección de casos y proporcionar el tratamiento adecuado.

Neisseria gonorrhoeae (N. gonorrhoeae) is the causal agent of gonorrhea, a sexually transmitted infection (STI) that is the second most common cause of STIs worldwide, causing high morbidity and cost in health care. In recent decades, reports of strains resistant to penicillin, fluoroquinolones, sulfonamides, tetracycline, macrolides, and more recently to azithromycin and extended-spectrum cephalosporins such as ceftriaxone and cefixime have increased worldwide. The main objective of this study was to determine the sensitivity to antimicrobials in N. gonorrhoeae strains that were sent to the Central Laboratory of Public Health (LCSP), by the collaborating centers of the Antimicrobial Resistance Laboratory Surveillance Network (RAM). For this, a prospective cross-sectional study was carried out from January to December, 2021. One hundred eighty strains were characterized as N. gonorrhoeae, which were subjected to sensitivity tests, obtaining 48% resistance and 52% intermediate sensitivity to penicillin while 70% presented resistance to ciprofloxacin and 19% to tetracycline. Also, 100% sensitivity to ceftriaxone and cefixime was obtained. The most prevalent resistance phenotype was QRNG, associated with resistance to ciprofloxacin, followed by the PPNG-QRNG phenotype, associated with resistance to penicillin and ciprofloxacin. Given these findings and the global emergence of antimicrobial resistance, especially extended-spectrum cephalosporins, it is recommended that bacteriology laboratories fortify surveillance to support case detection and provide appropriate treatment.

Association Between the LZTFL1 rs11385942 Polymorphism and COVID-19 Severity in Colombian Population.

Genetic and non-genetic factors are responsible for the high interindividual variability in the response to SARS-CoV-2. Although numerous genetic polymorphisms have been identified as risk factors for severe COVID-19, these remain understudied in Latin-American populations. This study evaluated the association of non-genetic factors and three polymorphisms: ACE rs4646994, ACE2 rs2285666, and LZTFL1 rs11385942, with COVID severity and long-term symptoms by using a case-control design. The control group was composed of asymptomatic/mild cases (n = 61) recruited from a private laboratory, while the case group was composed of severe/critical patients (n = 63) hospitalized in the Hospital Universitario Mayor-Méderi, both institutions located in Bogotá, Colombia. Clinical follow up and exhaustive revision of medical records allowed us to assess non-genetic factors. Genotypification of the polymorphism of interest was performed by amplicon size analysis and Sanger sequencing. In agreement with previous reports, we found a statistically significant association between age, male sex, and comorbidities, such as hypertension and type 2 diabetes mellitus (T2DM), and worst outcomes. We identified the polymorphism LZTFL1 rs11385942 as an important risk factor for hospitalization (p < 0.01; OR = 5.73; 95% CI = 1.2-26.5, under the allelic test). Furthermore, long-term symptoms were common among the studied population and associated with disease severity. No association between the polymorphisms examined and long-term symptoms was found. Comparison of allelic frequencies with other populations revealed significant differences for the three polymorphisms investigated. Finally, we used the statistically significant genetic and non-genetic variables to develop a predictive logistic regression model, which was implemented in a Shiny web application. Model discrimination was assessed using the area under the receiver operating characteristic curve (AUC = 0.86; 95% confidence interval 0.79-0.93). These results suggest that LZTFL1 rs11385942 may be a potential biomarker for COVID-19 severity in addition to conventional non-genetic risk factors. A better understanding of the impact of these genetic risk factors may be useful to prioritize high-risk individuals and decrease the morbimortality caused by SARS-CoV2 and future pandemics.

Crosstalk between Body Microbiota and the Regulation of Immunity.

The microbiome corresponds to the genetic component of microorganisms (archaea, bacteria, phages, viruses, fungi, and protozoa) that coexist with an individual. During the last two decades, research on this topic has become massive demonstrating that in both homeostasis and disease, the microbiome plays an important role, and in some cases, a decisive one. To date, microbiota have been identified at different body locations, such as the eyes, lung, gastrointestinal and genitourinary tracts, and skin, and technological advances have permitted the taxonomic characterization of resident species and their metabolites, in addition to the cellular and molecular components of the host that maintain a crosstalk with local microorganisms. Here, we summarize recent studies regarding microbiota residing in different zones of the body and their relationship with the immune system. We emphasize the immune components underlying pathological conditions and how they interact with local (and distant) microbiota.

Neuropilin-1 is present on Foxp3+ T regulatory cell-derived small extracellular vesicles and mediates immunity against skin transplantation.

Among the mechanisms of suppression that T regulatory (Treg) cells exert to control the immune responses, the secretion of small extracellular vesicles (sEV) has been recently proposed as a novel contact-independent immunomodulatory mechanism. Previous studies have demonstrated that Treg cells produce sEV, including exosomes, able to modulate the effector function of CD4+ T cells, and antigen presenting cells (APCs) such as dendritic cells (DCs) through the transfer of microRNA, cytokines, the production of adenosine, among others. Previously, we have demonstrated that Neuropilin-1 (Nrp1) is required for Tregs-mediated immunosuppression mainly by impacting on the phenotype and function of effector CD4+ T cells. Here, we show that Foxp3+ Treg cells secrete sEV, which bear Nrp1 in their membrane. These sEV modulate effector CD4+ T cell phenotype and proliferation in vitro in a Nrp1-dependent manner. Proteomic analysis indicated that sEV obtained from wild type (wt) and Nrp1KO Treg cells differed in proteins related to immune tolerance, finding less representation of CD73 and Granzyme B in sEV obtained from Nrp1KO Treg cells. Likewise, we show that Nrp1 is required in Treg cell-derived sEV for inducing skin transplantation tolerance, since a reduction in graft survival and an increase on M1/M2 ratio were found in animals treated with Nrp1KO Treg cell-derived sEV. Altogether, this study describes for the first time that Treg cells secrete sEV containing Nrp1 and that this protein, among others, is necessary to promote transplantation tolerance in vivo via sEV local administration.

Enhanced T-Cell Priming and Improved Anti-Tumor Immunity through Lymphatic Delivery of Checkpoint Blockade Immunotherapy.

An infusion of checkpoint blockade immunotherapy (CBI) has revolutionized cancer treatments for some patients, but the majority of patients experience disappointing responses. Because adaptive immune responses are mounted by the concentrated assembly of antigens, immune cells, and mediators in the secluded and protective environment of draining lymph nodes (dLNs), we hypothesize that lymphatic delivery of CBI (αCTLA-4 and αPD-1) to tumor dLNs (tdLNs) improves anti-tumor responses over intravenous (i.v.) administration, and that vaccination against tumor associated antigen (TAA) further enhances these responses. Mono- and combination CBI were administered i.v. or through image-guided intradermal (i.d.) injection to reach tdLNs in vaccinated and unvaccinated animals bearing either primary or orthotopically metastasizing B16F10 melanoma. Vaccination and boost against TAA, Melan-A, was accomplished with virus-like particles (VLP) directed to tdLNs followed by VLP boost after CBI administration. Lymphatic delivery of CBIs reduced primary tumor size and metastatic tumor burden, alleviated the pro-tumorigenic immune environment, and improved survival over systemic administration of CBIs. Animals receiving CBIs lymphatically exhibited significantly enhanced survival over those receiving therapies administered partially or completely through systemic routes. By combining vaccination and CBI for effective T-cell priming in the protected environment of dLNs, anti-tumor responses may be improved.

Serogrupos y resistencia antimicrobiana de Neisseria meningitidis causantes de enfermedad invasiva en Paraguay

RESUMEN La enfermedad meningocócica representa un problema de salud pública y una de las principales causas de morbilidad y mortalidad en todo el mundo. Los serogrupos que causan la mayor carga de enfermedad a nivel global son A, B, C, W e Y. El objetivo del estudio fue describir los serogrupos y la resistencia antimicrobiana de Neisseria meningitidis aisladas de enfermedad invasiva en Paraguay durante el periodo 2010-2020. Se estudiaron todas las muestras de líquido cefalorraquídeo y sangre con aislamientos o detección de ADN por PCR de N. meningitidis de pacientes de diversas edades, que fueron remitidas al Laboratorio Central de Salud Pública durante el periodo 2010-2020, dentro del marco de la vigilancia epidemiológica de meningitis (n=163) en Paraguay. La mayor frecuencia de hallazgos de N. meningitidis se observó en el grupo de edad de < 1 año. El 25,7% de los casos correspondió al serogrupo B, el 52,1% al serogrupo C, 18,4% al serogrupo W y 3,7% al serogrupo Y. En el 2018, se evidenció la mayor cantidad de casos por serogrupo C (n=27). La menor frecuencia de sensibilidad disminuida a penicilina G fue en el 2010 (12,5%) y la mayor en el 2014 (100,0%). Se registró un aumento de casos por serogrupo C a partir del 2017, posicionándose como serogrupo prevalente hasta el 2020, y además, un aumento de la sensibilidad disminuida a la penicilina. La vigilancia es de importancia en el control de la enfermedad meningocócica para detección de brotes, estimación de la carga de enfermedad, análisis de resistencia antimicrobiana, distribución de serogrupos y evaluaciones de estrategias de control.

ABSTRACT Meningococcal disease represents a public health problem and one of the main causes of morbidity and mortality worldwide. The serogroups that cause the highest burden of disease globally are A, B, C, W, and Y. The aim of the study was to describe serogroups and antimicrobial resistance of Neisseria meningitidis isolated from invasive disease in Paraguay during the 2010-2020 period. Samples of cerebrospinal fluid and blood with isolates or detection of DNA by PCR of N. meningitidis from patients of different ages referred to the Central Public Health Laboratory during the period 2010-2020 within the framework of the epidemiological surveillance of meningitis (n = 163) in Paraguay were studied. The highest frequency of N. meningitidis findings was observed in the <1 year age group, 25.7% of the cases corresponded to serogroup B, 52.1% to serogroup C, 18.4% to serogroup W and 3.7% to serogroup Y. In 2018, the highest number of cases by serogroup C (n = 27) was found. The lowest frequency of decreased sensitivity to penicillin G was in 2010 (12.5%) and the highest in 2014 (100.0%). There was an increase in cases due to serogroup C in 2017, positioning itself as the prevalent serogroup until 2020, in addition, there was an increase in decreased sensitivity to penicillin. Surveillance is important in the control of meningococcal disease for outbreak detection, estimation of the burden of disease, analysis of antimicrobial resistance, serogroup distribution, and evaluations of control strategies.

A micro-CT analysis of radicular dentine thickness in mandibular first premolars presenting C-shaped root canals: Identification of potential danger zones.

AIM: To describe the radicular dentine thickness in mandibular first premolars presenting C-shaped root canals, to identify the canal walls with less thickness as potential danger zones. In addition, to describe the internal and external anatomical characteristics of these teeth and associate them with the dentine thickness. METHODOLOGY: A total of 70 mandibular first premolars presenting C-shaped root canals were examined. Their internal morphology was analysed using Vertucci's and Fan's criteria, and their external morphology was analysed using the ASUDAS score. Besides, the dentine thickness around the root canals was two/three-dimensionally determined at five root planes and quantified in the distal and the mesial aspects. RESULTS: According to Fan's, ASUDAS, and Vertucci's classifications, the most common canal configurations were category C3, grade 3, and type V, respectively. In Vertucci's type III anatomy, the mesial root wall of the lingual canal showed significantly less dentine thickness than the distal wall in the middle plane (p = .031). Similarly, in Vertucci's type V anatomy, significantly less dentine thickness was observed in the mesial root wall of the buccal and lingual canals in the middle plane (p < .001) and the buccal canal in the middle-apical plane (p = .014) than the distal root wall of these canals. In teeth with ASUDAS grade 3 and 4 scores, significantly less dentine thickness was observed in the mesial in comparison with the distal root wall of these canals. These differences were demonstrated in the middle and middle-apical planes (p < .001) of grade 3 teeth and the middle-apical plane (p < .001) of grade 4 teeth. In these root planes, the Ver1-AS3 and VerV-AS3 combinations presented a 4-times greater risk of presenting walls with a critical dentine thickness of 0.6 mm (odds ratio [OR] = 4, p = .025) than the combinations Ver1-AS2, VerV-AS2, VerV-AS4, and VerIII-AS3. CONCLUSIONS: The root canal system configuration of mandibular first premolars with C-shaped canals showed a wide range of anatomical variations. The lowest dentine thickness was located in the mesial wall of the canals in the middle and apical root thirds of Vertucci's type III and V anatomies and in teeth with deep radicular grooves scored as ASUDAS grades 3 and 4. In the middle and middle-apical planes, the presence of the combinations Ver1-AS3 and VerV-AS3 showed a high risk of presenting a critical dentine thickness of 0.6 mm. Therefore, these root canal walls with less dentine thickness represent potential instrumentation danger zones in mandibular first premolars with C-shaped canals.