IFN-γ stimulates Paneth cell secretion through necroptosis mTORC1 dependent.

Immune mediators affect multiple biological functions of intestinal epithelial cells (IECs) and, like Paneth and Paneth-like cells, play an important role in intestinal epithelial homeostasis. IFN-γ a prototypical proinflammatory cytokine disrupts intestinal epithelial homeostasis. However, the mechanism underlying the process remains unknown. In this study, using in vivo and in vitro models we demonstrate that IFN-γ is spontaneously secreted in the small intestine. Furthermore, we observed that this cytokine stimulates mitochondrial activity, ROS production, and Paneth and Paneth-like cell secretion. Paneth and Paneth-like secretion downstream of IFN-γ, as identified here, is mTORC1 and necroptosis-dependent. Thus, our findings revealed that the pleiotropic function of IFN-γ also includes the regulation of Paneth cell function in the homeostatic gut.

The Impact of Major Earthquakes on Students' Emotional Distress and Internalizing Symptoms, Externalizing Behaviors, and Coping During the Implementation of keepin' it REAL-Mexico.

This article reports on effects of two earthquakes in Mexico on adolescents attending middle school. The earthquakes struck in close succession during the implementation of a school-based prevention program, providing an opportunity to assess emotional distress due to the earthquakes and whether the life skills taught in the program affected how students coped with the natural disaster. The objectives were to (1) evaluate the earthquakes' impact on students' distress; (2) assess if distress is associated with internalizing symptomology and externalizing behaviors; and (3) investigate if students receiving the original and adapted versions of the intervention coped better with the events. A Mexico-US research team culturally adapted keepin' it REAL to address connections between substance use among early adolescents in Mexico and exposure to violence. A random sample of public middle schools from three cities (Mexico City, Guadalajara, and Monterrey), stratified by whether they held morning or afternoon sessions, was selected. A total of 5522 7th grade students from 36 schools participated in the study. Students answered pretest and posttest questionnaires; the latter assessed earthquake-related distress and coping strategies. Earthquake-related distress was associated with all measures of undesired internalizing symptomology and externalizing behaviors. Compared to controls, students in the adapted intervention reported less aggressive and rule-breaking externalizing behavior and less violence perpetration. However, these intervention effects were not moderated by the level of earthquake-related distress, and they were not mediated by positive or negative coping. The findings have implications for prevention intervention research and policy as natural and human-made disasters occur more often.

Cytotoxicity Activity of Some meso-Dihydroguaiaretic Acid Derivatives and Mode of Action of the Most Active Compound.

The aim of this study was to screen sixteen meso-1 semi-synthetic derivatives bearing ether, esther, carbamate, phosphate or aminoether functional groups against five cancer cell lines: MCF-7 (breast), A549 (lung), HepG2 (liver), HeLa (cervix), and DU145 (prostate) at 25 µM using the MTT assay. Results from the screening showed that two derivatives had the lowest percentage of cell viability at 25 µM, the aminoether derivative meso-11 and the esther derivative meso-20 against A549 (44.15±0.78 %) and MCF-7 (41.60±0.92 %), respectively. Then, it was determined the IC50 value of each compound against their most sensitive cancer cell line. Results showed that aminoether derivative meso-11 showed potent cytotoxicity against A549 (IC50 =17.11±2.11 µM), whereas it resulted more cytotoxic against the LL-47 lung normal cell line (IC50 =9.49±1.19 µM) having a Selective Index (SI) of 0.55. On the other hand, the esther derivative meso-20 exhibited potent activity against MCF-7 (IC50 =18.20±1.98 µM), whereas it displayed moderate cytotoxicity against the MCF-10 breast normal cell line (IC50 =41.22±2.17 µM) with a SI of 2.2. Finally, studies on the mechanism of action of meso-20 indicated disruption of MCF-7 plasma membrane in vitro and the AMPK activation in silico.

Wet anaerobic digestion of organic fraction of municipal solid waste: experience with long-term pilot plant operation and industrial scale-up.

This paper presents the analysis of a pilot anaerobic digestion plant that operates with organic fraction of municipal solid waste (OFMSW) from a wholesale market and can treat up to 500 kg d-1. The process was monitored for a period of 524 days during which the residue was characterized and the biogas production and methane content were recorded. The organic load rate (OLR) of volatile solids (VS) was 0.89 kg m-3 d-1 and the Hydraulic Retention Time (HRT) was 25 d during the process. The yield was 82 Nm3 tons OFMSW-1 biogas, equivalent to 586 Nm3 tons CH4 VS-1. The results obtained in the pilot plant were used to carry out a technical-economic evaluation of a plant that treats 50 tons of OFMSW from wholesale markets. A production of 3769 Nm3 d-1 of biogas and 2080 Nm3 d-1 of methane is estimated, generating 35.1 MWh d-1 when converted to electricity.

Mesenchymal Stem Cells from Familial Alzheimer's Patients Express MicroRNA Differently.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the predominant form of dementia globally. No reliable diagnostic, predictive techniques, or curative interventions are available. MicroRNAs (miRNAs) are vital to controlling gene expression, making them valuable biomarkers for diagnosis and prognosis. This study examines the transcriptome of olfactory ecto-mesenchymal stem cells (MSCs) derived from individuals with the PSEN1(A431E) mutation (Jalisco mutation). The aim is to determine whether this mutation affects the transcriptome and expression profile of miRNAs and their target genes at different stages of asymptomatic, presymptomatic, and symptomatic conditions. Expression microarrays compare the MSCs from mutation carriers with those from healthy donors. The results indicate a distinct variation in the expression of miRNAs and mRNAs among different symptomatologic groups and between individuals with the mutation. Using bioinformatics tools allows us to identify target genes for miRNAs, which in turn affect various biological processes and pathways. These include the cell cycle, senescence, transcription, and pathways involved in regulating the pluripotency of stem cells. These processes are closely linked to inter- and intracellular communication, vital for cellular functioning. These findings can enhance our comprehension and monitoring of the disease's physiological processes, identify new disorder indicators, and develop innovative treatments and diagnostic tools for preventing or treating AD.

Socioeconomic Inequalities in Alcohol and Tobacco Consumption: A National Ecological Study in Mexican Adolescents.

Alcohol and cigarettes are the psychoactive substances that adolescents use most frequently. When both addictions are combined, they carry the worst burden of disease globally. The objective of this study was to identify whether socioeconomic factors correlate with alcohol and tobacco consumption in Mexican adolescents aged 10 years or more and to establish the relationship in the consumption between the two substances. This ecological study utilized data describing alcohol and tobacco consumption among adolescents aged 10-16 years (n = 48,837 ≈ N = 11,621,100). Having ever consumed any alcohol-containing beverage constituted alcohol consumption. Smoking a cigarette within 30 days constituted cigarette consumption. For both variables, the state-level percentages reported in the survey were used. Diverse socioeconomic variables were collected from official sources. Data on the prevalence of tobacco use and alcohol consumption were entered into an Excel database estimated for each of the states of the Mexican Republic, as well as the socioeconomic variables. We performed the analysis using Stata 14. Consumption prevalence was 15.0% for alcohol and 4.2% for tobacco. Alcohol consumption was not correlated with any studied socioeconomic variable (p > 0.05). The prevalence of tobacco consumption among elementary school students correlated (p < 0.05) with the portion of the population living in private dwellings without sewage, drainage, or sanitation (r = 0.3853). The prevalence of tobacco consumption among middle-school adolescents correlated with the portion of the employed population that earned up to two minimum wages (r = 0.3960), the percentage in poverty by income 2008 (r = 0.4754) and 2010 (r = 0.4531), and the percentage in extreme poverty by income 2008 (r = 0.4612) and 2010 (r = 0.4291). Positive correlations were found between tobacco consumption and alcohol consumption among both elementary (r = 0.5762, p=0.0006) and middle-school children (r = 0.7016, p=0.0000). These results suggest that certain socioeconomic factors correlate with tobacco consumption but not alcohol consumption. A correlation between alcohol consumption and tobacco consumption was observed. The results can be used for developing interventions in adolescents.

The Proteome Profile of Olfactory Ecto-Mesenchymal Stem Cells-Derived from Patients with Familial Alzheimer's Disease Reveals New Insights for AD Study.

Alzheimer's disease (AD), the most common neurodegenerative disease and the first cause of dementia worldwide, has no effective treatment, and its pathological mechanisms are not yet fully understood. We conducted this study to explore the proteomic differences associated with Familial Alzheimer's Disease (FAD) in olfactory ecto-mesenchymal stem cells (MSCs) derived from PSEN1 (A431E) mutation carriers compared with healthy donors paired by age and gender through two label-free liquid chromatography-mass spectrometry approaches. The first analysis compared carrier 1 (patient with symptoms, P1) and its control (healthy donor, C1), and the second compared carrier 2 (patient with pre-symptoms, P2) with its respective control cells (C2) to evaluate whether the protein alterations presented in the symptomatic carrier were also present in the pre-symptom stages. Finally, we analyzed the differentially expressed proteins (DEPs) for biological and functional enrichment. These proteins showed impaired expression in a stage-dependent manner and are involved in energy metabolism, vesicle transport, actin cytoskeleton, cell proliferation, and proteostasis pathways, in line with previous AD reports. Our study is the first to conduct a proteomic analysis of MSCs from the Jalisco FAD patients in two stages of the disease (symptomatic and presymptomatic), showing these cells as a new and excellent in vitro model for future AD studies.

Vachellia farnesiana Pods or a Polyphenolic Extract Derived from Them Exert Immunomodulatory, Metabolic, Renoprotective, and Prebiotic Effects in Mice Fed a High-Fat Diet.

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.

Knowledge, attitudes, perceptions, and COVID-19 hesitancy in a large public university in Mexico city during the early vaccination rollout.

BACKGROUND: Vaccination against COVID-19 is a primary tool for controlling the pandemic. However, the spread of vaccine hesitancy constitutes a significant threat to reverse progress in preventing the disease. Studies conducted in Mexico have revealed that vaccination intention in Mexico among the general population ranges from 62 to 82%. OBJECTIVE: To know the prevalence of COVID-19 vaccine hesitancy and associated factors among academics, students, and administrative personnel of a public university in Mexico City. METHODS: We administered an online survey investigating sociodemographic aspects, knowledge, attitudes, practices, and acceptance/hesitancy regarding the COVID-19 vaccine. Using generalized linear Poisson models, we analyzed factors associated with vaccine hesitancy, defined as not intending to be vaccinated within the following six months or refusing vaccination. RESULTS: During May and June 2021, we studied 840 people, prevalence of vaccine hesitancy was 6%. Hesitancy was significantly associated with fear of adverse effects, distrust of physician's recommendations, lack of knowledge regarding handwashing, age younger than 40 years, refusal to use face masks, and not having received influenza vaccination during the two previous seasons. CONCLUSIONS: Vaccine hesitancy in this population is low. Furthermore, our results allowed us the identification of characteristics that can improve vaccine promotion.

The Feasibility, Acceptability, and Utility of Mantente REAL: the Culturally Adapted Version of keepin' it REAL for Mexico.

A binational team of investigators culturally adapted, implemented, and tested the efficacy in Mexico of keepin' it REAL, a US-designed prevention intervention for youth. This article reports on the social validity of the adapted intervention by assessing its feasibility, acceptability, and utility, as perceived by participating middle school students, teachers/implementers, and school administrators. Middle schools (N = 36) were randomly assigned to (1) the culturally adapted version for Mexico (Mantente REAL), (2) the original intervention from the USA (keepin' it REAL) translated into Spanish, or (3) a control condition (treatment as usual). Adult and child feedback about the adapted and original versions of the intervention indicate that both are feasible to implement in the Mexican context. Implementation fidelity was equally high for both versions of the manualized intervention. Students, however, were more satisfied with the culturally adapted version than with the non-adapted version. They reported gaining more knowledge, finding it more acceptable, applicable, and authentic, and they reported discussing the program with their family and friends more often. The findings support the feasibility of engaging classroom teachers to implement manualized prevention programs in Mexico. These findings also advance prevention science by documenting the importance of cultural adaptation as a means to increase students' identification with and acceptability of efficacious school-based interventions. The article discusses the practice, policy, and future prevention research implications of the findings for Mexico and their potential generalizability to other middle- and lower-income countries.

Molecular docking, SAR analysis and biophysical approaches in the study of the antibacterial activity of ceramides isolated from Cissus incisa.

The developing of antibacterial resistance is becoming in crisis. In this sense, natural products play a fundamental role in the discovery of antibacterial agents with diverse mechanisms of action. Phytochemical investigation of Cissus incisa leaves led to isolation and characterization of the ceramides mixture (1): (8E)-2-(tritriacont-9-enoyl amino)-1,3,4-octadecanetriol-8-ene (1-I); (8E)-2-(2',3'-dihydroxyoctacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-II); (8E)-2-(2'-hydroxyheptacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-III); and (8E)-2-(-2'-hydroxynonacosanoyl amino)-1,3,4-octadecanetriol-8-ene (1-IV). Until now, this is the first report of the ceramides (1-I), (1-II), and (1-IV). The structures were elucidated using NMR and mass spectrometry analyses. Antibacterial activity of ceramides (1) and acetylated derivates (2) was evaluated against nine multidrug-resistant bacteria by Microdilution method. (1) showed the best results against Gram-negatives, mainly against carbapenems-resistant Acinetobacter baumannii with MIC = 50 µg/mL. Structure-activity analysis and molecular docking revealed interactions between plant ceramides with membrane proteins, and enzymes associated with biological membranes of Gram-negative bacteria, through hydrogen bonding of functional groups. Vesicular contents release assay showed the capacity of (1) to disturb membrane permeability detected by an increase of fluorescence probe over time. The membrane disruption is not caused for ceramides lytic action on cell membranes, according in vitro hemolyticactivity results. Combining SAR analysis, bioinformatics and biophysical techniques, and also experimental tests, it was possible to explain the antibacterial action of these natural ceramides.

Keepin' It REAL-Mantente REAL in Mexico: a Cluster Randomized Controlled Trial of a Culturally Adapted Substance Use Prevention Curriculum for Early Adolescents.

This study assesses the efficacy of a version of the keepin' it REAL (kiREAL) substance use prevention curriculum for middle school students that was culturally adapted for Mexico, renamed Mantente REAL (MREAL), and tested in a cluster randomized controlled trial in Mexico's three largest cities. Student participants were in 7th grade in public middle schools (N = 5523, 49% female, mean age = 11.9). A representative sample of 12 schools from each city, stratified by whether they held morning or afternoon sessions, was randomized to three conditions: culturally adapted MREAL, original kiREAL translated into Spanish, or a treatment-as-usual control group. Regular classroom teachers were trained to deliver the adapted MREAL or the kiREAL manualized curricula. Students with active parental consent completed pretest and post-test questionnaires, 7-8 months apart, at the beginning and end of the 2017-2018 academic year. We assessed the MREAL intervention, relative to kiREAL and controls, with general linear models adjusted for baseline, attrition (24%), non-normal distributions, stratification by city, and school-level clustering. Among students already using the substance more often at pretest, MREAL students had relatively more desirable outcomes, compared to kiREAL and/or to controls, in recent use of alcohol, cigarettes, "hard drugs," heavy episodic drinking, and intoxication. MREAL students reported relatively less violence victimization and perpetration of bullying and relatively more use of three of the intervention's REAL drug resistance strategies (Explain, Avoid, Leave). The adapted version of kiREAL for Mexico showed numerous desired outcomes in areas deliberately targeted in the cultural adaptation. Full protocol can be accessed through Clinical Trials.gov. ID: NCT03233386, "'Keepin' It REAL in Mexico: An adaptation and multisite RCT".

Dyslipidemia and severe periodontitis among patients with type 2 diabetes.

Not available.

Bioassay-Guided Identification of the Antiproliferative Compounds of Cissus trifoliata and the Transcriptomic Effect of Resveratrol in Prostate Cancer Pc3 Cells.

The bioassay-guided fractionation of a CHCl3-MeOH extract from the stems of Cissus trifoliata identified an active fraction against PC3 prostate cancer cells. The treatment for 24 h showed an 80% reduction in cell viability (p ≤ 0.05) by a WST-1 assay at a concentration of 100 µg/mL. The HPLC-QTOF-MS analysis of the fraction showed the presence of coumaric and isoferulic acids, apigenin, kaempferol, chrysoeriol, naringenin, ursolic and betulinic acids, hexadecadienoic and octadecadienoic fatty acids, and the stilbene resveratrol. The exposure of PC3 cells to resveratrol (IC25 = 23 µg/mL) for 24 h induced significant changes in 847 genes (Z-score ≥ ±2). The functional classification tool of the DAVID v6.8 platform indicates that the underlying molecular mechanisms against the proliferation of PC3 cells were associated (p ≤ 0.05) with the process of differentiation and metabolism. These findings provide experimental evidence suggesting the potential of C. trifoliata as a promising natural source of anticancer compounds.

Cytotoxic Fractions from Hechtia glomerata Extracts and p-Coumaric Acid as MAPK Inhibitors.

Preliminary bioassay-guided fractionation was performed to identify cytotoxic compounds from Hechtia glomerata, a plant that is used in Mexican ethnomedicine. Organic and aqueous extracts were prepared from H. glomerata's leaves and evaluated against two cancer cell lines. The CHCl3/MeOH (1:1) active extract was fractionated, and the resulting fractions were assayed against prostate adenocarcinoma PC3 and breast adenocarcinoma MCF7 cell lines. Active fraction 4 was further analyzed by high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry analysis to identify its active constituents. Among the compounds that were responsible for the cytotoxic effects of this fraction were flavonoids, phenolic acids, and aromatic compounds, of which p-coumaric acid (p-CA) and its derivatives were abundant. To understand the mechanisms that underlie p-CA cytotoxicity, a microarray assay was performed on PC3 cells that were treated or not with this compound. The results showed that mitogen-activated protein kinases (MAPKs) that regulate many cancer-related pathways were targeted by p-CA, which could be related to the reported effects of reactive oxygen species (ROS). A molecular docking study of p-CA showed that this phenolic acid targeted these protein active sites (MAPK8 and Serine/Threonine protein kinase 3) at the same binding site as their inhibitors. Thus, we hypothesize that p-CA produces ROS, directly affects the MAPK signaling pathway, and consequently causes apoptosis, among other effects. Additionally, p-CA could be used as a platform for the design of new MAPK inhibitors and re-sensitizing agents for resistant cancers.

Synthesis and in vitro evaluation of antimycobacterial and cytotoxic activity of new α,ß-unsaturated amide, oxazoline and oxazole derivatives from l-serine.

The synthesis of 19 compounds derived from l-serine and analogs of p-substituted cinnamic acid is reported. Oxazolines 9 and oxazoles 10 have high antitubercular activity with Minimum Inhibitory Concentration (MIC) of 0.7812-25.0 µg/mL (3.21-100.3 µM), against two strains of Mycobacterium tuberculosis sensitive to first-line drugs Isoniazid (INH), Rifampicin (RIF), Ethambutol (EMB), Pyrazinamide (PZE) (H37Rv) and a clinical isolate resistant to INH, RIF and EMB (G122). The cytotoxic evaluation shows that oxazoles have low activity, finding viability>96% against the VERO cell line. The results show these compounds could be considered as future alternatives for antitubercular treatment.

Social determinants for overweight and obesity in a highly marginalized population from Comitán, Chiapas, Mexico.

OBJECTIVE: We assessed the prevalence of overweight and obesity and its association with some social determinants in a highly marginalized population in Mexico. MATERIALS AND METHODS: Cross-sectional study conducted in Comitán, Chiapas, from 2010 to 2012, comprising 1 858 subjects aged ≥20 years. We evaluated proximal, intermediate, and structuralsocial determinants. RESULTS: The prevalence of overweight and obesity was 37.9 and 16.5%, respectively. The probability of overweight and obesity was higher in participants with ≥primary school, self-reported non-indigenous origin, and medium level of marginalization compared with those with

OBJETIVO: Estimar la prevalencia de sobrepeso y obesidad y su asociación con determinantes sociales en población con alto grado de marginación. MATERIAL Y MÉTODOS: Estudio transversal realizado en Comitán, Chiapas, de 2010 a 2012, que incluyó 1 858 sujetos ≥20 años de edad. Se evaluaron determinantes sociales proximales, intermedios y estructurales. RESULTADOS: La prevalencia de sobrepeso y obesidad fue de 37.9 y 16.5%, respectivamente. La probabilidad de sobrepeso y obesidad fue mayor en sujetos con escolaridad ≥primaria, en sujetos que se autodefinieron como no indígenas y en sujetos con un grado de marginación medio comparado con individuos con escolaridad

Metabolic Profile and Evaluation of Biological Activities of Extracts from the Stems of Cissus trifoliata.

Cissus trifoliata (L.) L belongs to the Vitaceae family and is an important medicinal plant used in Mexico for the management of infectious diseases and tumors. The present study aimed to evaluate the metabolic profile of the stems of C. trifoliata and to correlate the results with their antibacterial and cytotoxic activities. The hexane extract was analyzed using gas chromatography coupled with mass spectrometry (GC-MS) and the CHCl3-MeOH and aqueous extracts by ultraperformance liquid chromatography quadrupole time of fly mass spectrometry (UPLC-QTOF-MS). The antibacterial activity was determined by broth microdilution and the cytotoxicity was evaluated using MTS cell proliferation assay. Forty-six metabolites were putatively identified from the three extracts. Overall, terpenes, flavonoids and stilbenes characterize the metabolic profile. No antibacterial activity was found in any extract against the fifteen bacteria strains tested (MIC >500 µg/mL). However, high cytotoxic activity (IC50 ≤ 30 µg/mL) was found in the hexane and aqueous extracts against hepatocarcinoma and breast cancer cells (Hep3B, HepG2 and MCF7). This is the first report of the bioactive compounds of C. trifoliata stems and their antibacterial and cytotoxic properties. The metabolic profile rich in anticancer compounds correlate with the cytotoxic activity of the extracts from the stems of C. trifoliata. This study shows the antitumor effects of this plant used in the traditional medicine and justifies further research of its anticancer activity.

DISPERSION OF A NEW CORONAVIRUS SARS-COV-2 BY AIRLINES IN 2020: TEMPORAL ESTIMATES OF THE OUTBREAK IN MEXICO.

BACKGROUND: On January 23, 2020, China imposed a quarantine on the city of Wuhan to contain the SARS-CoV-2 outbreak. Regardless of this measure, the new infection has spread to several countries around the world. OBJECTIVE: We developed a method to study the dissemination of this infection by airline routes and provide estimations of the time of arrival of the outbreak to different cities. METHODS: Using the Kermack and McKendrick model complemented with diffusion on a graph composed of nodes and edges, we made an analysis of COVID-19 dispersion to other cities by air travel. RESULTS: The estimation was accurate in that it was possible to predict in the middle of February 2020 the arrival of the first outbreak in Mexico, which eventually occurred between March 20 and 30. This estimation was robust with respect to small changes in epidemiological parameters at the other nodes. CONCLUSIONS: The estimation of the time of arrival of the outbreak from its epicenter, allows for a time period to implement and strengthen preventive measures aimed at the general population as well as to strengthen hospital infrastructure and training of human resources. In the present study, this estimation was accurate, as observed from the real data of the beginning of the outbreak in Mexico City up to April 6, 2020.

Modeling Antibacterial Activity with Machine Learning and Fusion of Chemical Structure Information with Microorganism Metabolic Networks.

Predicting the activity of new chemical compounds over pathogenic microorganisms with different metabolic reaction networks (MRN s) is an important goal due to the different susceptibility to antibiotics. The ChEMBL database contains >160 000 outcomes of preclinical assays of antimicrobial activity for 55 931 compounds with >365 parameters of activity (MIC, IC50, etc.) and >90 bacteria strains of >25 bacterial species. In addition, the Leong and Barabàsi data set includes >40 MRNs of microorganisms. However, there are no models able to predict antibacterial activity for multiple assays considering both drug and MRN structures at the same time. In this work, we combined perturbation theory, machine learning, and information fusion techniques to develop the first PTMLIF model. The best linear model found presented values of specificity = 90.31/90.40 and sensitivity = 88.14/88.07 in training/validation series. We carried out a comparison to nonlinear artificial neural network (ANN) techniques and previous models from the literature. Next, we illustrated the practical use of the model with an experimental case of study. We reported for the first time the isolation and characterization of terpenes from the plant Cissus incisa. The antibacterial activity of the terpenes was experimentally determined. The more active compounds were phytol and α-amyrin, with MIC = 100 µg/mL for Vancomycin-resistant Enterococcus faecium and Acinetobacter baumannii resistant to carbapenems. These compounds are already known from other sources. However, they have been isolated and evaluated for the first time here against several strains of multidrug-resistant bacteria including World Health Organization (WHO) priority pathogens. Last, we used the model to predict the activity of these compounds versus other microorganisms with different MRNs in order to find other potential targets.