Gestational Diabetes Mellitus Subtypes Classified by Oral Glucose Tolerance Test and Maternal and Perinatal Outcomes: Results of a Mexican Multicenter Prospective Cohort Study "Cuido Mi Embarazo".

Purpose: This study explores the impact of gestational diabetes mellitus (GDM) subtypes classified by oral glucose tolerance test (OGTT) values on maternal and perinatal outcomes. Patients and Methods: This multicenter prospective cohort study (May 2019-December 2022) included participants from the Mexican multicenter cohort study Cuido mi Embarazo (CME). Women were classified into four groups per 75-g 2-h OGTT: 1) normal glucose tolerance (normal OGTT), 2) GDM-Sensitivity (isolated abnormal fasting or abnormal fasting in combination with 1-h or 2-h abnormal results), 3) GDM-Secretion (isolated abnormal values at 1-h or 2-h or their combination), and 4) GDM-Mixed (three abnormal values). Cesarean delivery, neonates large for gestational age (LGA), and pre-term birth rates were among the outcomes compared. Between-group comparisons were analyzed using either the t-test, chi-square test, or Fisher's exact test. Results: Of 2,056 Mexican pregnant women in the CME cohort, 294 (14.3%) had GDM; 53.7%, 34.4%, and 11.9% were classified as GDM-Sensitivity, GDM-Secretion, and GDM-Mixed subtypes, respectively. Women with GDM were older (p = 0.0001) and more often multiparous (p = 0.119) vs without GDM. Cesarean delivery (63.3%; p = 0.02) and neonate LGA (10.7%; p = 0.078) were higher in the GDM-Mixed group than the overall GDM group (55.6% and 8.4%, respectively). Pre-term birth was more common in the GDM-Sensitivity group than in the overall GDM group (10.2% vs 8.5%, respectively; p=0.022). At 6 months postpartum, prediabetes was more frequent in the GDM-Sensitivity group than in the overall GDM group (31.6% vs 25.5%). Type 2 diabetes was more common in the GDM-Mixed group than in the overall GDM group (10.0% vs 3.3%). Conclusion: GDM subtypes effectively stratified maternal and perinatal risks. GDM-Mixed subtype increased the risk of cesarean delivery, LGA, and type 2 diabetes postpartum. GDM subtypes may help personalize clinical interventions and optimize maternal and perinatal outcomes.

Predicting the dispersal and invasion dynamics of ambrosia beetles through demographic reconstruction and process-explicit modeling.

Evaluating potential routes of invasion of pathogens and vectors of sanitary importance is essential for planning and decision-making at multiple scales. An effective tool are process-explicit models that allow coupling environmental, demographic and dispersal information to evaluate population growth and range dynamics as a function of the abiotic conditions in a region. In this work we simulate multiple dispersal/invasion routes in Mexico that could be taken by ambrosia beetles and a specific symbiont, Harringtonia lauricola, responsible for a severe epiphytic of Lauraceae in North America. We used Xyleborus bispinatus Eichhoff 1868 as a study subject and estimated its demography in the laboratory in a temperature gradient (17, 20, 26, 29, 35 °C), which we then used to parameterize a process-based model to estimate its metapopulation dynamics. The maximum intrinsic growth rate of X. bispinatus is 0.13 with a thermal optimum of 26.2 °C. The models suggest important regions for the establishment and dispersal the states of Veracruz, Chiapas and Oaxaca (high host and secondary vectors diversity), the Isthmus of Tehuantepec (connectivity region), and Michoacán and Jalisco (important avocado plantations). The use of hybrid process-based models is a promising tool to refine the predictions applied to the study of biological invasions and species distributions.

Isolation and identification of metallotolerant bacteria with a potential biotechnological application.

Mining has led to severe environmental pollution in countries with exhaustive mining production and inadequate industrial waste regulation. Microorganisms in contaminated sites, like mine tailings, have adapted to high concentrations of heavy metals, developing the capacity of reducing or removing them from these environments. Therefore, it is essential to thoroughly characterize bacteria present in these sites to find different ways of bioremediation. In this regard, in this study, an enrichment and isolation procedure were performed to isolate bacteria with lower nutritional requirements and high tolerance to Cu(II) and Fe(II) from two Sonoran River basin mining tails. Two Staphylococcus species and a Microbacterium ginsengisoli strain were isolated and identified from the San Felipe de Jesús mining tail. Also, three strains were isolated from the Nacozari de García mining tail: Burkholderia cenocepacia, Sphingomonas sp. and Staphylococcus warneri. Significant microbiological differences were found between the two sites. All these species exhibited tolerance up to 300 mg/L for Cu (II)-Fe (II) solutions, indicating their capacity to grow in these conditions. Moreover, a consortium of isolated bacteria was immobilized in two different biocomposites and the biocomposite with larger pore size achieved greater bacterial immobilization showcasing the potential of these bacteria in biotechnological applications.

Personal and Psychological Traits of University-Going Women That Affect Opportunities and Entrepreneurial Intentions.

The purpose of this research is to analyze how personality traits and psychological profiles influence the detection of entrepreneurial opportunities by, and the intentions of, university-going women in the northwest region of Mexico. It also examines how business opportunities are decisive when it comes to awakening entrepreneurial intention. The moderating and mediating effects of the detection of business opportunities and the psychological profile are also examined with respect to the direct relationship between personal traits and entrepreneurial intentions. For this study, information was collected from 1197 students attending the Autonomous University of Baja California and the Technological Institute of Sonora through a digital survey (Google Forms) distributed via email during the second half of 2022. The PLS-SEM statistical technique was used to test the hypotheses of the proposed theoretical model. The results revealed that personality traits have positive and significant effects on the psychological profile and on business opportunities. However, it was clearly observed that one's personal traits and psychological profile have little or no influence on entrepreneurial intentions. We also found that the psychological profile is the construct that most influences business opportunities. In addition, it was also highlighted that business opportunities contribute to awakening the entrepreneurial intentions of university-going women. On the other hand, it was revealed that business opportunities have a negative moderating effect on the relationship between the psychological profile and entrepreneurial intentions. Likewise, this study has shown that the detection of business opportunities and the psychological profile have indirect effects on the relationship between the personal traits and the entrepreneurial intentions of university-going women. This research contributes to the development and strengthening of trait theory, the theory of reasoned action, and the theory of planned behavior.

The influence of humidity and temperature on the vertical richness and abundance of blood-sucking flies (Culicidae and Ceratopogonidae) in a montane cloud forest in Mexico.

Because the vertical distribution and diversity of blood-sucking flies are poorly known, we determined the diversity, structure, and composition of culicids between vertical vegetation strata. We evaluated the influence of microclimatic variables during different times of the day over a year. We used eight CDC traps baited with CO2 at a height of 1.5 m and 12-15 m. We conducted rank-abundance curves, similarity analysis (ANOSIM and SIMPER), and multivariate clustering with incidence and abundance data. We used GAM models to analyze the influence of strata (understory vs canopy), humidity, and temperature on insect richness and abundance. During the day, the difference between strata was mainly due to higher abundance of Wyeomyia arthrostigma and Wyeomyia ca. adelpha in the understory. During the night, the differences were mainly due to higher abundance of Culex stigmatosoma, Culex salinarius, and Aedes allotecnon in the canopy, and Wyeomyia arthrostigma in the understory. Seasonality played a role in the similarity between the strata. Diversity during the day was positively related to humidity and temperature, and nocturnal diversity increased with temperature but decreased with higher humidity. The effects of environmental factors on the spatiotemporal distribution of fly species are essential for epidemiological surveillance.

Psychometric properties of ability to contribute measurements as a domain of functional ability of older persons: a COSMIN systematic review.

BACKGROUND: Older person's ability to contribute covers contributions divided into five subdomains: assisting friends and neighbours, mentoring peers and younger people, caring for family, engaging in the workforce and voluntary activity. OBJECTIVE: To evaluate the psychometric properties of ability to contribute measurements as a domain of functional ability of older persons using Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology for systematic reviews. METHODS: A systematic search was performed in PubMed, Embase and PsycINFO databases, for observational studies published within the last 10 years. The measurement properties of these ability measures were evaluated against the COSMIN taxonomy. Risk-of-bias assessment was performed using the COSMIN Risk of Bias checklist. RESULTS: Of the 32,665 studies identified, we selected 19, of which the main purpose was to develop or validate an instrument or have related items that measure at least one of the subdomains. None of the instruments contained items that were fully related to the five subdomains, 60% (n = 12) were related to voluntary activities and 15% (n = 3) to mentoring peers and younger people. As for psychometric properties, two studies assessed content validity. Factor analysis was used to evaluate structural validity in 10 studies. Internal consistency was evaluated in 63% of the instruments and Cronbach's alpha ranges from 0.63 to 0.92. No study reported predictive validity. A very limited overview of their scope and limitations for their application was observed. CONCLUSIONS: We found no single instrument measuring all subdomains of ability to contribute. We found several instruments containing items that could indirectly measure some of the subdomains of the ability to contribute.

Sex differences in the influence of type 2 diabetes (T2D)-related genes, parental history of T2D, and obesity on T2D development: a case-control study.

BACKGROUND: This study investigated the effect of sex and age at type 2 diabetes (T2D) diagnosis on the influence of T2D-related genes, parental history of T2D, and obesity on T2D development. METHODS: In this case-control study, 1012 T2D cases and 1008 healthy subjects were selected from the Diabetes in Mexico Study database. Participants were stratified by sex and age at T2D diagnosis (early, ≤ 45 years; late, ≥ 46 years). Sixty-nine T2D-associated single nucleotide polymorphisms were explored and the percentage contribution (R2) of T2D-related genes, parental history of T2D, and obesity (body mass index [BMI] and waist-hip ratio [WHR]) on T2D development was calculated using univariate and multivariate logistic regression models. RESULTS: T2D-related genes influenced T2D development most in males who were diagnosed early (R2 = 23.5%; females, R2 = 13.5%; males and females diagnosed late, R2 = 11.9% and R2 = 7.3%, respectively). With an early diagnosis, insulin production-related genes were more influential in males (76.0% of R2) while peripheral insulin resistance-associated genes were more influential in females (52.3% of R2). With a late diagnosis, insulin production-related genes from chromosome region 11p15.5 notably influenced males while peripheral insulin resistance and genes associated with inflammation and other processes notably influenced females. Influence of parental history was higher among those diagnosed early (males, 19.9%; females, 17.5%) versus late (males, 6.4%; females, 5,3%). Unilateral maternal T2D history was more influential than paternal T2D history. BMI influenced T2D development for all, while WHR exclusively influenced males. CONCLUSIONS: The influence of T2D-related genes, maternal T2D history, and fat distribution on T2D development was greater in males than females.

The prevalence of diabetes worldwide is slightly higher in men than in women, particularly in those aged 50 or younger (16.5% for men versus 13.5% for women). This suggests that hormonal differences could be critical in early development of Type 2 diabetes. Some known factors previously associated with T2D, such as genes, parental history of diabetes and obesity, could have a differential influence between both sexes for the development of T2D. We compared these factors between 1008 healthy individual and 1012 TD2 patients. In this comparison, we calculated the percentage of variability of the disease explained by each factor. As expected, the most noticeable differences between men and women were observed in T2D diagnoses before age 46. Genes had a greater effect in men than in women (23.5% vs. 13.5%). While genes involved in insulin production have a greater influence on men, genes involved in peripheric insulin resistance have a greater influence on women. The overall parental history of T2D influences similarly in males (19.9%) and females (17.5%), however, the unilateral genetic influence of the mother was much greater in males than in females. The influence of global and abdominal obesity played a greater role in men than in women. In T2D diagnoses after age of 45, the influence of genes and parental history of diabetes decreases markedly, and the relative influence of global obesity augments. However, while genes linked to insulin resistance and inflammation predominate in females, genes linked to insulin secretion predominate in males.

Antifungal and Insecticidal Activities of Selected Plant Species from Cloud Forest of Veracruz, Mexico: A Contribution to the Search of Novel Control Agents against Ambrosia Pest Complexes.

The antifungal and insecticidal activities of 34 extracts from 27 plant species were evaluated against fungal phytopathogens of the genus Fusarium and Xyleborus Scolytine ambrosia beetles involved in Fusarium dieback (FD) and laurel wilt (LW) diseases. Sixteen extracts caused mycelial growth inhibition (MGI) above 23 % at 2 mg mL-1 against F. solani, those from S. nudum and M. argyrophylla exhibited the highest MGI (57 % and 49 %, respectively). Thirteen extracts displayed significant antifungal activity against F. kuroshium, those from C. nocturnum and M. argyrophylla exhibited the highest MGI (100 % and 54.9 %, respectively). Additionally, ten plants extracts caused mortality in at least one of the beetle species tested, mainly from Solanaceae species. In the most active species, 39 phenolics were identified that may have contributed to their biological effects. This study is one of the first to report the potential of plant-derived natural products against the causative agents of FD and LW.

MIDO GDM: an innovative artificial intelligence-based prediction model for the development of gestational diabetes in Mexican women.

Given the barriers to early detection of gestational diabetes mellitus (GDM), this study aimed to develop an artificial intelligence (AI)-based prediction model for GDM in pregnant Mexican women. Data were retrieved from 1709 pregnant women who participated in the multicenter prospective cohort study 'Cuido mi embarazo'. A machine-learning-driven method was used to select the best predictive variables for GDM risk: age, family history of type 2 diabetes, previous diagnosis of hypertension, pregestational body mass index, gestational week, parity, birth weight of last child, and random capillary glucose. An artificial neural network approach was then used to build the model, which achieved a high level of accuracy (70.3%) and sensitivity (83.3%) for identifying women at high risk of developing GDM. This AI-based model will be applied throughout Mexico to improve the timing and quality of GDM interventions. Given the ease of obtaining the model variables, this model is expected to be clinically strategic, allowing prioritization of preventative treatment and promising a paradigm shift in prevention and primary healthcare during pregnancy. This AI model uses variables that are easily collected to identify pregnant women at risk of developing GDM with a high level of accuracy and precision.

Development and validation of a multivariable genotype-informed gestational diabetes prediction algorithm for clinical use in the Mexican population: insights into susceptibility mechanisms.

INTRODUCTION: Gestational diabetes mellitus (GDM) is underdiagnosed in Mexico. Early GDM risk stratification through prediction modeling is expected to improve preventative care. We developed a GDM risk assessment model that integrates both genetic and clinical variables. RESEARCH DESIGN AND METHODS: Data from pregnant Mexican women enrolled in the 'Cuido mi Embarazo' (CME) cohort were used for development (107 cases, 469 controls) and data from the 'Mónica Pretelini Sáenz' Maternal Perinatal Hospital (HMPMPS) cohort were used for external validation (32 cases, 199 controls). A 2-hour oral glucose tolerance test (OGTT) with 75 g glucose performed at 24-28 gestational weeks was used to diagnose GDM. A total of 114 single-nucleotide polymorphisms (SNPs) with reported predictive power were selected for evaluation. Blood samples collected during the OGTT were used for SNP analysis. The CME cohort was randomly divided into training (70% of the cohort) and testing datasets (30% of the cohort). The training dataset was divided into 10 groups, 9 to build the predictive model and 1 for validation. The model was further validated using the testing dataset and the HMPMPS cohort. RESULTS: Nineteen attributes (14 SNPs and 5 clinical variables) were significantly associated with the outcome; 11 SNPs and 4 clinical variables were included in the GDM prediction regression model and applied to the training dataset. The algorithm was highly predictive, with an area under the curve (AUC) of 0.7507, 79% sensitivity, and 71% specificity and adequately powered to discriminate between cases and controls. On further validation, the training dataset and HMPMPS cohort had AUCs of 0.8256 and 0.8001, respectively. CONCLUSIONS: We developed a predictive model using both genetic and clinical factors to identify Mexican women at risk of developing GDM. These findings may contribute to a greater understanding of metabolic functions that underlie elevated GDM risk and support personalized patient recommendations.

Single nucleotide variants in microRNA biosynthesis genes in Mexican individuals.

Background: MicroRNAs (miRNAs) are important regulators in a variety of biological processes, and their dysregulation is associated with multiple human diseases. Single nucleotide variants (SNVs) in genes involved in the processing of microRNAs may alter miRNA regulation and could present high allele heterogeneity in populations from different ethnic groups. Thus, the aim of this study was to genotype 15 SNVs in eight genes involved in the miRNA processing pathway in Mexican individuals and compare their frequencies across 21 populations from five continental groups. Methods: Genomic DNA was obtained from 399 healthy Mexican individuals. SNVs in AGO2 (rs2293939 and rs4961280), DGCR8 (rs720012), DICER (rs3742330 and rs13078), DROSHA (rs10719 and rs6877842), GEMIN3 (rs197388 and rs197414), GEMIN4 (rs7813, rs2740349, and rs4968104), TNRC6B (rs9611280), and XP05 (rs11077 and rs34324334) were genotyped using TaqMan probes. The minor allele frequency of each SNV was compared to those reported in the 1,000 Genomes database using chi-squared. Sankey plot was created in the SankeyMATIC package to visualize the frequency range of each variant in the different countries analyzed. Results: In Mexican individuals, all 15 SNVs were found in Hardy-Weinberg equilibrium, with frequencies ranging from 0.04 to 0.45. The SNVs rs4961280, rs2740349, rs34324334, and rs720012 in Mexican individuals had the highest minor allele frequencies worldwide, whereas the minor allele frequencies of rs197388, rs10719, rs197414, and rs1107 were among the lowest in Mexican individuals. The variants had high allele heterogeneity among the sub-continental populations, ranging from monomorphic, as was the case for rs9611280 and rs34324334 in African groups, to >0.50, which was the case for variants rs11077 and rs10719 in most of the populations. Importantly, the variants rs197388, rs720012, and rs197414 had FST values > 0.18, indicating a directional selective process. Finally, the SNVs rs13078 and rs10719 significantly correlated with both latitude and longitude. Conclusion: These data indicate the presence of high allelic heterogeneity in the worldwide distribution of the frequency of SNVs located in components of the miRNA processing pathway, which could modify the genetic susceptibility associated with human diseases in populations with different ancestry.

Association of loneliness and social isolation with all-cause mortality among older Mexican adults in the Mexican health and aging study: a retrospective observational study.

BACKGROUND: Plenty of evidence shows how social isolation and loneliness are associated with increased risk for numerous diseases and mortality. But findings about their interactive or combined effects on health outcomes and mortality remains inconclusive. OBJECTIVE: Analyze the longitudinal association of loneliness, social isolation and their interactions, with the all-cause mortality among older adults in Mexico. METHODS: A retrospective observational study was conducted. Mexican adults older than 50 years were included. Data from the Mexican Health and Aging Study (MHAS) in the 2015 and 2018 waves were used. The subjects were classified according to their level of loneliness and the presence of social isolation. Multivariate logistic regression analyzes were performed to determine the degree of association between loneliness and social isolation with all-cause mortality at a 3-year follow-up. RESULTS: From the total sample of 11,713 adults aged 50 years or over, 707 (6%) did not survive, 42% presented loneliness, and 53% were classified as socially isolated. After multivariate adjustment only social isolation (OR = 1.30, 95%CI:1.03-1.64) was associated with all-cause mortality, loneliness (Mild: OR = 0.83, 95%CI:0.59-1.16; Severe: OR = 1.03, 95%CI:0.71-1.64), and the interaction between loneliness and social isolation were not associated with all-cause mortality. CONCLUSION: Social isolation, but not loneliness or their interaction, was associated with all-cause mortality in Mexican adults older than 50 years. This finding may help direct possible future interventions that help improve mental health in older adults from a highly collectivistic country.

Novel clinical and immunological features associated with persistent post-acute sequelae of COVID-19 after six months of follow-up: a pilot study.

BACKGROUND: Currently, there is scant information regarding the features associated to the persistence of post-COVID-19 syndrome, which is the main aim of the present study. METHODS: A cohort study of 102 COVID-19 patients was conducted. The post-COVID-19 symptoms were assessed by a standardised questionnaire. Lymphocyte immunophenotyping was performed by flow cytometry and chemokines/cytokines, neutrophil extracellular traps, the tripartite motif 63, anti-cellular, and anti-SARS-CoV-2 IgG antibodies were addressed in serum. The primary outcome was the persistence of post-COVID-19 syndrome after six months follow-up. RESULTS: Thirteen patients (12.7%) developed the primary outcome and had a more frequent history of post-COVID-19 syndrome 3 months after infection onset (p = .044), increased levels of IL-1α (p = .011) and IP-10 (p = .037) and increased CD57 expression in CD8+ T cells (p = .003). There was a trend towards higher levels of IFN-γ (p = .051), IL-1ß (p = .062) and IL-6 (p = .087). The history of post COVID-19 in the previous 3 months, obesity, baseline serum MIP-1α and IP-10, and CD57 expression in CD8+ T cells were independently associated with the persistence of post-COVID-19 syndrome. CONCLUSION: Our data suggest an important relationship between a pro-inflammatory state mediated through metabolic pathways related to obesity and increased cellular senescence as a key element in the persistence of post-COVID-19 syndrome at six months of follow-up.

Microorganisms Associated with the Ambrosial Beetle Xyleborus affinis with Plant Growth-Promotion Activity in Arabidopsis Seedlings and Antifungal Activity Against Phytopathogenic Fungus Fusarium sp. INECOL_BM-06.

Plants interact with a great diversity of microorganisms or insects throughout their life cycle in the environment. Plant and insect interactions are common; besides, a great variety of microorganisms associated with insects can induce pathogenic damage in the host, as mutualist phytopathogenic fungus. However, there are other microorganisms present in the insect-fungal association, whose biological/ecological activities and functions during plant interaction are unknown. In the present work evaluated, the role of microorganisms associated with Xyleborus affinis, an important beetle species within the Xyleborini tribe, is characterized by attacking many plant species, some of which are of agricultural and forestry importance. We isolated six strains of microorganisms associated with X. affinis shown as plant growth-promoting activity and altered the root system architecture independent of auxin-signaling pathway in Arabidopsis seedlings and antifungal activity against the phytopathogenic fungus Fusarium sp. INECOL_BM-06. In addition, evaluating the tripartite interaction plant-microorganism-fungus, interestingly, we found that microorganisms can induce protection against the phytopathogenic fungus Fusarium sp. INECOL_BM-06 involving the jasmonic acid-signaling pathway and independent of salicylic acid-signaling pathway. Our results showed the important role of this microorganisms during the plant- and insect-microorganism interactions, and the biological potential use of these microorganisms as novel agents of biological control in the crops of agricultural and forestry is important.

Diagnostic Accuracy of Capillary Blood Glucometer Testing for Gestational Diabetes.

Purpose: Few pregnant women in low-resource settings are screened for gestational diabetes mellitus (GDM) using the gold standard oral glucose tolerance test (OGTT). This study compared capillary blood glucose testing with 2-h plasma glucose measurements obtained using the 75-g OGTT to screen for GDM at primary healthcare clinics in Mexico. Patients and Methods: Pregnant women who participated in a previous prospective multicenter longitudinal cohort study and who had not been previously diagnosed with diabetes were included. Participants were evaluated using the plasmatic 2-h 75-g OGTT with simultaneous capillary blood glucose measurements using a glucometer. The study endpoint was the comparability of the glucometer results to the gold standard OGTT when collected simultaneously. Sensitivity, specificity, and area under the curve of the glucose measurements obtained for capillary blood compared with venous plasma (gold standard) were calculated to determine diagnostic accuracy. Results: The study included 947 pregnant women who had simultaneous glucose measurements available (blood capillary [glucometer] and venous blood OGTT). Overall, capillary blood glucose testing was very sensitive (89.47%); the specificity was 66.58% and the area under the curve (95% confidence interval) was 0.78 (0.74-0.81). The sensitivity, specificity and area under the curve of each capillary measurement were: 89.47%, 66.58% and 0.78 (0.74-0.82) for the fasting measurement, 91.53%, 93.24% and 0.92 (0.88-0.96) for the one-hour measurement, and 89.80%, 93.32%, 0.91 (0.87-0.95) for the second-hour measurement, respectively. No adverse events were reported. Conclusion: Capillary OGTT is a valid alternative to the gold standard OGTT for screening of GDM in low-resource situations or in situations where there are other limitations to performing the OGTT as part of primary healthcare services.

MIDO COVID: A digital public health strategy designed to tackle chronic disease and the COVID-19 pandemic in Mexico.

Screening, prevention, and management of non-communicable diseases (NCDs, including obesity, hypertension, and type 2 diabetes) is the core function of Integrated Measurement for Early Detection (MIDO), a digital strategy developed by the Carlos Slim Foundation in Mexico. An extension of this strategy, MIDO COVID, was developed to address the need for an integrated plan in primary health care during the COVID-19 pandemic. MIDO COVID facilitates planning, surveillance, testing, and clinical management of SARS-CoV-2 infections and the major NCDs and their pre-disease states, to streamline the continuum of care. MIDO COVID screening was applied in 1063 Carso Group workplaces in 190 municipalities of the 32 Mexican states. Staff were trained to screen healthy workers for NCDs using a questionnaire, anthropomorphic measurements, and blood work; healthy individuals returning to work also received a SARS-CoV-2 antibody test. Between June 26 and December 31, 2020, 58,277 asymptomatic individuals underwent screening. The prevalence of obesity, hypertension, and type 2 diabetes was 32.1%, 25.7%, and 9.7% respectively. Only 2.2%, 8.8%, and 4.5% of individuals, respectively, were previously aware of their condition. Pre-obesity was identified in 38.6%, pre-hypertension in 17.4%, and prediabetes in 7.5% of the population. Risk of SARS-CoV-2 infection was highest for individuals with multiple NCDs. Many Mexicans are unaware of their health status and potentially increased risk of COVID-19 and serious complications. As a universal strategy implemented regardless of social factors, MIDO COVID promotes equity in access to health care prevention and early stage detection of NCDs; the information gained may help inform decisionmakers regarding prioritising vulnerable populations for immunisation.

Discovery and optimization of orally bioavailable and potent plasma Kallikrein inhibitors bearing a quaternary carbon.

Hereditary angioedema (HAE) is a rare and potentially life-threatening disease that affects an estimated 1 in 50,000 individuals worldwide. Berotralstat (BCX7353) is the only small molecule approved by the US Food and Drug Administration (FDA) for the prophylactic treatment of HAE attacks in patients 12 years and older. During the discovery of BCX7353, we also identified a novel series of small molecules containing a quaternary carbon as potent and orally bioavailable Plasma Kallikrein (PKal) inhibitors. Lead compound was identified as a potent inhibitor following a detailed lead optimization process that balanced the lipophilic efficiency (LipE) and pharmacokinetic (PK) profile.

Scaffold hopping via ring opening enables identification of acyclic compounds as new complement Factor D inhibitors.

The three complement pathways comprising the early phase of the complement system (the classical, lectin, and alternative pathways) act together with the innate and adaptive immune systems to protect against foreign entities and maintain tissue homeostasis. While these systems are normally under tight regulatory control, several diseases have been reported to correlate with uncontrolled activation and amplification of the alternative pathway, including paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, C3 glomerulopathy, and age-related macular degeneration. Complement FactorD (CFD), a serine protease, is the rate-limiting enzyme for the activity of alternative pathway. CFD activates the alternative pathway by cleaving Complement Factor B complexed to C3b (C3bB) to generate alternative pathway C3 convertase (C3bBb). In our search for novel CFD inhibitors with therapeutic potential, we employed a hot-spot analysis of an ensemble of apo and holo CFD structures. This analysis identified potential pharmacophore features that aided in the design of a series of compounds based on an l-proline core. While these compounds inhibited CFD in an esterolytic assay (for example, a proline-based compound, IC50 = 161 nM), the pharmacokinetic (PK) properties were poor. A strategy of scaffold hopping via ring opening led to a novel series of acyclic compounds, with subsequent structure-based ligand design and lead optimization producing several novel CFD inhibitors. One of these inhibitors, 1-(2-((2-(3-chloro-2-fluorobenzylamino)-2-oxoethyl)(cyclopropyl)amino)-2-oxoethyl)-5-(3-methyl-3-(1-methylpiperidin-4-yl)ureido)-1H-indazole-3-carboxamide, showed good potency with IC50s of 37 nM in the esterolytic assay and 30 nM in a hemolytic assay and PK assessments following oral administration to rats revealed a Cmax of 113 ng/mL and an AUC0-24h of 257 hr.ng/mL.

Clinical and immunological features associated to the development of a sustained immune humoral response in COVID-19 patients: Results from a cohort study.

Background: Until now, most of the research addressing long-term humoral responses in coronavirus disease 2019 (COVID-19) had only evaluated the serum titers of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgGs, without the assessment of the baseline antiviral clinical and immune profile, which is the aim of this study and may be the key factor leading to a broad and sustained antibody response. Methods: We included 103 patients with COVID-19. When the patients sought medical attention (baseline), a blood sample was drawn to perform immunophenotype of lymphocytes by flow cytometry. The patients were assessed 15 days after baseline and then every month until the third month, followed by a last visit 6 months after recruitment. We evaluated the anti-SARS-COV-2 IgG at all time points, and the serum levels of cytokines, chemokines, anti-cellular (AC) antibodies and neutrophil extracellular traps were also assessed during the follow-up. The primary outcome of the study was the presence of a sustained immune humoral response, defined as an anti-SARS-CoV-2 IgG titer >4.99 arbitrary units/mL in at least two consecutive measures. We used generalized lineal models to assess the features associated with this outcome and to assess the effect of the changes in the cytokines and chemokines throughout time on the development of a sustained humoral immune response. Results: At baseline the features associated to a sustained immune humoral response were the diagnosis of critical disease, absolute number of lymphocytes, serum IP-10, IL-4, IL-2, regulatory T cells, CD8+ T cells, and positive AC antibodies. Critical illness and the positivity of AC antibodies were associated with a sustained humoral immune response after 3 months, whilst critical illness and serum IL-13 were the explanatory variables after 6 months. Conclusion: A sustained immune humoral response is strongly related to critical COVID-19, which is characterized by the presence of AC antibodies, quantitative abnormalities in the T cell compartment, and the serum cytokines and chemokines during acute infection and throughout time.

In response to the comment on the article "Variability in case fatality rate risk due to Covid-19 according to health services provider in Mexico City hospitals"

Not available.