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.

Prediction of Higher Heating Values in Bio-Oil from Solvothermal Biomass Conversion and Bio-Oil Upgrading Given Discontinuous Experimental Conditions.

Both the conversion of lignocellulosic biomass to bio-oil (BO) and the upgrading of BO have been the targets of many studies. Due to the large diversity and discontinuity seen in terms of reaction conditions, catalysts, solvents, and feedstock properties that have been used, a comparison across different publications is difficult. In this study, machine learning modeling is used for the prediction of final higher heating value (HHV) and ΔHHV for the conversion of lignocellulosic feedstocks to BO, and BO upgrading. The models achieved coefficient of determination (R2) scores ranging from 0.77 to 0.86, and the SHapley Additive exPlanations (SHAP) values were used to obtain model explainability, revealing that only a few experimental parameters are largely responsible for the outcome of the experiments. In particular, process temperature and reaction time were overwhelmingly responsible for the majority of the predictions, for both final HHV and ΔHHV. Elemental composition of the starting feedstock or BO dictated the upper possible HHV value obtained after the experiment, which is in line with what is known from previous methodologies for calculating HHV for fuels. Solvent used, initial moisture concentration in BO, and catalyst active phase showed low predicting power, within the context of the data set used. The results of this study highlight experimental conditions and variables that could be candidates for the creation of minimum reporting guidelines for future studies in such a way that machine learning can be fully harnessed.

Machine Learning Model Insights into Base-Catalyzed Hydrothermal Lignin Depolymerization.

Lignin, an abundant component of plant matter, can be depolymerized into renewable aromatic chemicals and biofuels but remains underutilized. Homogeneously catalyzed depolymerization in water has gained attention due to its economic feasibility and performance but suffers from inconsistently reported yields of bio-oil and solid residues. In this study, machine learning methods were used to develop predictive models for bio-oil and solid residue yields by using a few reaction variables and were subsequently validated by doing experimental work and comparing the predictions to the results. The models achieved a coefficient of determination (R2) score of 0.83 and 0.76, respectively, for bio-oil yield and solid residue. Variable importance for each model was calculated by two different methodologies and was tied to existing studies to explain the model predictive behavior. Based on the outcome of the study, the creation of concrete guidelines for reporting in lignin depolymerization studies was recommended. Shapley additive explanation value analysis reveals that temperature and reaction time are generally the strongest predictors of experimental outcomes compared to the rest.

Traditional Midwifery Contribution to Safe Birth in Cultural Safety: Narrative Evaluation of an Intervention in Guerrero, Mexico.

A 2017 randomised controlled trial in Guerrero State, Mexico, showed supporting Indigenous traditional midwives on their own terms improved traditional childbirths without inferior maternal health outcomes. This narrative evaluation complements the trial to document participant experience of safer birth in cultural safety, transformative dynamics and implementation issues of the intervention. Stories came from 26 traditional midwives, 28 apprentices, 12 intercultural brokers and 20 Indigenous women who experienced the intervention. Their accounts indicate the intervention revitalised traditional midwifery and consolidated local skills through traditional midwife apprentices and intercultural brokers to support safe birth. According to the stories, communities reintroduced traditional perinatal care and reported positive health impacts for mothers, children, and other adults, which contributed to early collaboration with official health services. Challenges included remuneration and disinterest of younger apprentices and brokers. The intervention seems to have improved interaction between traditional and Western services, setting the stage for further intercultural dialogue.

Safe birth in cultural safety in southern Mexico: a pragmatic non-inferiority cluster-randomised controlled trial.

BACKGROUND: Available research on the contribution of traditional midwifery to safe motherhood focuses on retraining and redefining traditional midwives, assuming cultural prominence of Western ways. Our objective was to test if supporting traditional midwives on their own terms increases cultural safety (respect of Indigenous traditions) without worsening maternal health outcomes. METHODS: Pragmatic parallel-group cluster-randomised controlled non-inferiority trial in four municipalities in Guerrero State, southern Mexico, with Nahua, Na savi, Me'phaa and Nancue ñomndaa Indigenous groups. The study included all pregnant women in 80 communities and 30 traditional midwives in 40 intervention communities. Between July 2015 and April 2017, traditional midwives and their apprentices received a monthly stipend and support from a trained intercultural broker, and local official health personnel attended a workshop for improving attitudes towards traditional midwifery. Forty communities in two control municipalities continued with usual health services. Trained Indigenous female interviewers administered a baseline and follow-up household survey, interviewing all women who reported pregnancy or childbirth in all involved municipalities since January 2016. Primary outcomes included childbirth and neonatal complications, perinatal deaths, and postnatal complications, and secondary outcomes were traditional childbirth (at home, in vertical position, with traditional midwife and family), access and experience in Western healthcare, food intake, reduction of heavy work, and cost of health care. RESULTS: Among 872 completed pregnancies, women in intervention communities had lower rates of primary outcomes (perinatal deaths or childbirth or neonatal complications) (RD -0.06 95%CI - 0.09 to - 0.02) and reported more traditional childbirths (RD 0.10 95%CI 0.02 to 0.18). Among institutional childbirths, women from intervention communities reported more traditional management of placenta (RD 0.34 95%CI 0.21 to 0.48) but also more non-traditional cold-water baths (RD 0.10 95%CI 0.02 to 0.19). Among home-based childbirths, women from intervention communities had fewer postpartum complications (RD -0.12 95%CI - 0.27 to 0.01). CONCLUSIONS: Supporting traditional midwifery increased culturally safe childbirth without worsening health outcomes. The fixed population size restricted our confidence for inference of non-inferiority for mortality outcomes. Traditional midwifery could contribute to safer birth among Indigenous communities if, instead of attempting to replace traditional practices, health authorities promoted intercultural dialogue. TRIAL REGISTRATION: Retrospectively registered ISRCTN12397283 . Trial status: concluded.

In many Indigenous communities, traditional midwives support mothers during pregnancy, childbirth, and some days afterwards. Research involving traditional midwives has focused on training them in Western techniques and redefining their role to support Western care. In Guerrero state, Mexico, Indigenous mothers continue to trust traditional midwives. Almost half of these mothers still prefer traditional childbirths, at home, in the company of their families and following traditional practices. We worked with 30 traditional midwives to see if supporting their practice allowed traditional childbirth without worsening mothers' health. Each traditional midwife received an inexpensive stipend, a scholarship for an apprentice and support from an intercultural broker. The official health personnel participated in a workshop to improve their attitudes towards traditional midwives. We compared 40 communities in two municipalities that received support for traditional midwifery with 40 communities in two municipalities that continued to receive usual services. We interviewed 872 women with childbirth between 2016 and 2017. Mothers in intervention communities suffered fewer complications during childbirth and had fewer complications or deaths of their babies. They had more traditional childbirths and fewer perineal tears or infections across home-based childbirths. Among those who went to Western care, mothers in intervention communities had more traditional management of the placenta but more non-traditional cold-water baths. Supporting traditional midwifery increased traditional childbirth without worsening health outcomes. The small size of participating populations limited our confidence about the size of this difference. Health authorities could promote better health outcomes if they worked with traditional midwives instead of replacing them.

Machine learning based analysis of reaction phenomena in catalytic lignin depolymerization.

Heterogeneously catalyzed lignin solvolysis opens the possibility of transforming low value biomass into high value, useful aromatic chemicals, however, its reaction behavior is poorly understood due to the many possible interactions between reaction parameters. In this study, a novel predictive model for bio-oil yield, char yield and reaction time is developed using Random Forest (RF) regression method using data available from the literature to study the impact of surface properties of the catalyst and the weight averaged molecular weight of the lignin (Mw) used in the reaction. The models achieved a coefficient of determination (R2) score of 0.9062, 0.9428 and 0.8327, respectively, and feature importance for each case was explained and tied to studies that provide a mechanistic explanation for the performance of the model. Surface properties and lignin Mw showed no importance to the prediction of bio-oil yield and average pore diameter contributed 3% of feature importance to reaction time.

Larrea tridentata and its Biological Activities.

BACKGROUND: Larrea tridentata is a dominant shrub in the deserts of North America and is recognized for its various traditional uses. More than 50 traditional uses have been recorded. Regarding its chemical composition, the products of the mevalonate, shikimate, and malonate pathways are predominant. L. tridentata has nordihydroguaiaretic acid (NDGA), one of its most studied secondary metabolites that exhibited remarkable different biological activities: sequestration of reactive oxygen species, inhibition of lipoxygenases (LOX) and activation of the endogenous antioxidant response mediated by nuclear factor erythroid 2-related factor 2 (NRF2). OBJECTIVE AND METHODS: This review seeks to draw attention to metabolites other than NDGA and which also contribute to the various biological activities of L. tridentata. Therefore, the present review includes those reports focused on the pharmacological properties of the organic extracts of L. tridentata and its natural products with promising values. RESULTS AND CONCLUSION: Among the most promising and widely reported metabolites from L. tridentata, are: 3'-demethoxy-6-O-demethylisoguaiacin, 3'-O-methyldihydroguaiaretic acid, meso-dihydroguaiaretic acid, and tetra-O-methylnordihydroguaiaretic acid. These have been reported to exhibit antibacterial, antiprotozoal, anthelmintic, antifungal, antiviral, anticancer, and antioxidant activities.

Antibacterial and cytotoxic activities of new sphingolipids and other constituents isolated from Cissus incisa leaves.

Cissus incisa is used in traditional Mexican medicine to treat certain ailments, infectious or cancerous diseases. Excepting for our previous research, this species had no scientific reports validating its traditional use. In this study, we evaluated the antibacterial and cytotoxic properties of the sphingolipids and others phytocompounds isolated from C. incisa leaves to increase the scientific knowledge of the Mexican flora. The antibacterial activity was evaluated against Gram-positive and Gram-negative bacteria by the Microdilution method. Meanwhile, the cytotoxic potential was determined on six human cancer cells: PC3, Hep3B, HepG2, MCF7, A549, and HeLa; using an aqueous solution cell proliferation assay kit. A cell line of immortalized human hepatocytes (IHH) was included as a control of non-cancerous cells. Selectivity index (SI) was determined only against the hepatocellular carcinoma cell lines. The phytochemical investigation of C. incisa leaves resulted in the isolation and characterization of five compounds: 2-(2'-hydroxydecanoyl amino)-1,3,4-hexadecanotriol-8-ene (1), 2,3-dihydroxypropyl tetracosanoate (2), ß-sitosterol-D-glucopyranoside (3), α-amyrin-3-O-ß-D-glucopyranoside (4), and a mixture of cerebrosides (5). Until now, this is the first report of the sphingolipids (1), (5-IV) and (5-V). Only the compound (4) and cerebrosides (5) exhibited antibacterial activity reaching a MIC value of 100 µg/mL against Pseudomonas aeruginosa resistant to carbapenems. While, the acetylated derivate of (3), compound (3Ac) showed the best cytotoxic result against PC3 (IC50 = 43 ± 4 µg/mL) and Hep3B (IC50 = 49.0 ± 4 µg/mL) cancer cell lines. Likewise, (3Ac) achieved better SI values on HepG2 and Hep3B cell lines. This research reveals the importance of study medicinal plants, to identify bioactive molecules as sources of potential drugs. The presence of these compounds allows us to justify the use of this plant in traditional Mexican medicine.

Descripción demográfica, bioquímica y sintomática según los estadios reproductivos STRAW+10 en mujeres mexicanas en la peri y posmenopausia / Demographic, biochemical and symptomatic description according to STRAW + 10 reproductive stages in Mexican women in peri and postmenopause

Resumen OBJETIVO: Categorizar el perfil demográfico, bioquímico y sintomático de la población mexicana atendida en el Instituto Nacional de Perinatología para describir su comportamiento en los estadios del envejecimiento reproductivo. MATERIALES Y MÉTODOS: Estudio transversal y descriptivo efectuado entre junio y diciembre de 2018 en pacientes de la Clínica de peri y posmenopausia del Instituto Nacional de Perinatología. Criterios de inclusión: mujeres mayores de 41 años con diagnóstico de peri y posmenopausia, clasificadas según STRAW+10 en tres categorías: Categoría 1 (-2 a -1), Categoría 2 (+1A a +1C) y Categoría 3 (+2). Para el análisis estadístico se obtuvieron medidas de tendencia central, χ2 y ANOVA para el análisis inferencial. RESULTADOS: Se estudiaron 741 pacientes peri y posmenopáusicas, con edad promedio a la menopausia de 50.08 años. El promedio de edad poblacional fue de 57.11 años, con un índice de masa corporal promedio de 27.92, con 56.2% de la población en límites de obesidad. La comorbilidad más frecuente fue la hipertensión arterial y el síntoma más reportado, los bochornos, más prevalentes durante la transición a la menopausia. CONCLUSIONES: El sistema STRAW+10 es una manera clínica y objetiva de estadificar a las pacientes en transición a la menopausia. Es importante emprender más estudios poblacionales en mujeres para describir el comportamiento del envejecimiento reproductivo en México.

Abstract OBJECTIVE: Categorize the demographic, biochemical and symptomatic profile of the Mexican population served at the Instituto Nacional de Perinatología to describe their behavior in the stages of reproductive aging. MATERIALS AND METHODS: The following is an observational, descriptive, cross sectional study women from the Peri- and Postmenopause clinic at the National Institute of Perinatology in Mexico that enrolled 741 women over 41 years of age with a diagnosis of menopause according to the STRAW+10 criteria and classified in three categories: Category 1 (-2 to -1), Category 2 (+1A to +1C), and Category 3 (+2). The statistical analysis was performed by measure of central tendency, χ2 and ANOVA for the inferential analysis. RESULTS: In our population of 741 women, the average age at menopause was 50.08 years, while the population's age average was 57.11 years. Average body mass index was 27.92 kg/m2, with 56.2% of the population within obesity range. The most prevalent comorbidity was arterial hypertension and the most frequent symptom was hot flushes. Hot flushes were most prevalent during the transition to menopause. CONCLUSIONS: The STRAW+10 is an objective way to clinically classify patients in transition to menopause. There is an important need for more population-based studies in women to describe the reproductive ageing behavior in Mexico.

Resident Knowledge and Perception of Pain Management.

Chronic pain involves a complex mechanism that afflicts 50 million adults in the United States and incurs societal costs upwards of $560 billion annually. The consequences of this epidemic have resulted in an epidemic of its own, with the opioid crisis becoming a top priority in healthcare. Historically, the sub-optimal practices of overprescribing opioids and inadequate monitoring of iatrogenic addiction have contributed to this problem. If progress is to be made in this area, it is imperative that we examine how future physicians are being trained to manage pain. We examined internal medicine resident knowledge regarding pain as well as their satisfaction with medical school preparation in this regard using two surveys: The Knowledge and Attitudes Survey Regarding Pain (KASRP) and The Medical School Pain Curriculum Survey (MSPCS). Residents scored an overall 60.7% on the knowledge assessment survey, and less than 50% of respondents agreed that their medical school curriculum had prepared them sufficiently. This suggests that improvements can be made in medical school curricula regarding pain management education to better train physicians on how to manage pain, particularly in an era that demands expertise in this area.

Pathogen Risk Analysis for Wild Amphibian Populations Following the First Report of a Ranavirus Outbreak in Farmed American Bullfrogs (Lithobates catesbeianus) from Northern Mexico.

Ranaviruses are the second deadliest pathogens for amphibian populations throughout the world. Despite their wide distribution in America, these viruses have never been reported in Mexico, the country with the fifth highest amphibian diversity in the world. This paper is the first to address an outbreak of ranavirus in captive American bullfrogs (Lithobates catesbeianus) from Sinaloa, Mexico. The farm experienced high mortality in an undetermined number of juveniles and sub-adult bullfrogs. Affected animals displayed clinical signs and gross lesions such as lethargy, edema, skin ulcers, and hemorrhages consistent with ranavirus infection. The main microscopic lesions included mild renal tubular necrosis and moderate congestion in several organs. Immunohistochemical analyses revealed scant infected hepatocytes and renal tubular epithelial cells. Phylogenetic analysis of five partial ranavirus genes showed that the causative agent clustered within the Frog virus 3 clade. Risk assessment with the Pandora⁺ protocol demonstrated a high risk for the pathogen to affect amphibians from neighboring regions (overall Pandora risk score: 0.619). Given the risk of American bullfrogs escaping and spreading the disease to wild amphibians, efforts should focus on implementing effective containment strategies and surveillance programs for ranavirus at facilities undertaking intensive farming of amphibians.

Nuclear magnetic resonance spectroscopy data of isolated compounds from Acacia farnesiana (L) Willd fruits and two esterified derivatives.

In the present article we describe the spectroscopic data of 1H and 13C Nuclear Magnetic Resonance of 11 compounds including: Nine natural products from the hexanic-chloroformic and methanolic extracts of Acacia farnesiana fruit and two esterified derivatives (22E-stimasta-5,22-dien- 3ß-acetyl and methyl 3,4,5-triacetyloxybenzoate). Data linked to the research work entitled "Chemical composition of fruits of Acacia farnesiana (L) Willd and its activity against Mycobacterium tuberculosis and dysentery bacteria" (Hernández et al., 2019) [1].

Chemical composition of Acacia farnesiana (L) wild fruits and its activity against Mycobacterium tuberculosis and dysentery bacteria.

ETHNOPHARMACOLOGICAL RELEVANCE: In Mexico, plants are an important element of traditional medicine, and many are considered part of Mexican cultural heritage from prehispanic and colonial times. Nevertheless, relatively few systematic scientific studies have been conducted to fully characterize the chemical composition and pharmacological activities of Mexican medicinal plants. Acacia farnesiana is used in Mexican traditional medicine to treat dysentery and tuberculosis and therefore could have bioactive compounds that may explain its traditional use. AIMS OF THE STUDY: i) To isolate and characterize the compounds from the hexanic, chloroformic and methanolic extracts; ii) to identify the volatile compounds from methylated hexanic and chloroformic extracts using GC-FID and GC-MS methods; iii) to identify the compounds from methanolic and aqueous extracts using HPLC-Q-TOF-MS; iv) to test the activity of extracts and isolated compounds against Mycobacterium tuberculosis and dysentery bacteria. MATERIAL AND METHODS: A. farnesiana fruits were collected in Acatlán de Osorio, Puebla, Mexico. Hexanic, chloroformic, methanolic and aqueous extracts were prepared and analyzed by different chromatographic techniques including column chromatography, flash chromatography, GC-FID, GC-MS and HPLC-Q-TOF-MS. Structural elucidation was carried out by NMR spectroscopic analysis. The activity of extracts, phytochemicals and semi-synthetic derivatives against Mycobacterium tuberculosis H37Rv and G122 as well as dysentery bacteria (Campylobacter jejuni, Shigella flexneri, Salmonella enteritidis, Yersinia enterocolitica and enterohemorrhagic Escherichia coli) was determined by the broth microdilution method and reported as minimal inhibitory concentration (MIC µg/mL). RESULTS: From both hexane and chloroform extracts, tetracosanoic acid (2S)-2,3-dihydroxypropyl ester (1) and (3ß,22E)-estigmasta-5,22-dien-3-yl ß-D-glucopyranoside (2) were isolated and characterized. From the methanolic extract, methyl gallate (3), gallic acid (4), (3ß,22E)-estigmasta-5,22-dien-3-yl ß-D-glucopyranoside (2), (2S) naringenin 7-O-ß-glucopyranoside (prunin, 5), pinitol (6) and sucrose (7) were isolated and characterized. Furthermore, hexanic and chloroformic extracts were analyzed by GC-FID and GC-MS and 18 methylated fatty acids were identified for each extract in addition to three sterols. The methanolic and aqueous extracts were analyzed separately by HPLC-Q-TOF-MS, and 15 compounds were identified in each extract. The compounds 1, 2, and 7, in addition to 13 fatty acids and eight phenolic compounds, were identified for the first time in A. farnesiana. The extracts showed antitubercular (MIC 100-200 µg/mL) and antidysentery activity (MIC 100-200 µg/mL). Methyl gallate and its acetylated derivative showed activity against the sensible strain M. tuberculosis H37Rv with MIC values of 50-25 µg/mL, respectively. The flavanone prunin showed activity against multidrug resistant M. tuberculosis G122 (MIC 50 µg/mL). Methyl gallate, gallic acid and prunin showed activity against C. jejuni (MIC 50 µg/mL). CONCLUSIONS: The activity of tested extracts and isolated compounds against M. tuberculosis and dysentery bacteria justifies the ethnomedical use of A. farnesiana fruits for the treatment of tuberculosis and dysentery.

Signaling Events Downstream of AHR Activation That Contribute to Toxic Responses: The Functional Role of an AHR-Dependent Long Noncoding RNA (slincR) Using the Zebrafish Model.

BACKGROUND: A structurally diverse group of chemicals, including dioxins [e.g., 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)] and polycyclic aromatic hydrocarbons (PAHs), can xenobiotically activate the aryl hydrocarbon receptor (AHR) and contribute to adverse health effects in humans and wildlife. In the zebrafish model, repression of sox9b has a causal role in several AHR-mediated toxic responses, including craniofacial cartilage malformations; however, the mechanism of sox9b repression remains unknown. We previously identified a long noncoding RNA, sox9b long intergenic noncoding RNA (slincR), which is increased (in an AHR-dependent manner) by multiple AHR ligands and is required for the AHR-activated repression of sox9b. OBJECTIVE: Using the zebrafish model, we aimed to enhance our understanding of the signaling events downstream of AHR activation that contribute to toxic responses by identifying: a) whether slincR is enriched on the sox9b locus, b) slincR's functional contributions to TCDD-induced toxicity, c) PAHs that increase slincR expression, and d) mammalian orthologs of slincR. METHODS: We used capture hybridization analysis of RNA targets (CHART), qRT-PCR, RNA sequencing, morphometric analysis of cartilage structures, and hemorrhaging screens. RESULTS: The slincR transcript was enriched at the 5' untranslated region (UTR) of the sox9b locus. Transcriptome profiling and human ortholog analyses identified processes related to skeletal and cartilage development unique to TCDD-exposed controls, and angiogenesis and vasculature development unique to TCDD-exposed zebrafish that were injected with a splice-blocking morpholino targeting slincR. In comparison to TCDD exposed control morphants, slincR morphants exposed to TCDD resulted in abnormal cartilage structures and a smaller percentage of animals displaying the hemorrhaging phenotype. In addition, slincR expression was significantly increased in six out of the sixteen PAHs we screened. CONCLUSION: Our study establishes that in zebrafish, slincR is recruited to the sox9b 5' UTR to repress transcription, can regulate cartilage development, has a causal role in the TCDD-induced hemorrhaging phenotype, and is up-regulated by multiple environmentally relevant PAHs. These findings have important implications for understanding the ligand-specific mechanisms of AHR-mediated toxicity. https://doi.org/10.1289/EHP3281.

Associations with perineal trauma during childbirth at home and in health facilities in indigenous municipalities in southern Mexico: a cross-sectional cluster survey.

BACKGROUND: Episiotomy and perineal tears remain common in vaginal deliveries. This study estimated the frequency of and factors associated with perineal tears, episiotomies, and postnatal infections among women in two predominantly indigenous municipalities in southern Mexico, where traditional midwives play an important role in women's health. METHODS: A cross-sectional study contacted women who gave birth in the previous three years. An administered questionnaire asked about place of delivery, birthing position, birth attendant, episiotomy, perineal tears, and wound infection after delivery. Cluster adjusted bivariate and then multivariate analysis examined factors potentially associated with self-reported perineal trauma (episiotomy and/or perineal tear). Key informant interviews sought insights into some of the findings. RESULTS: Among women with a vaginal delivery, 71% (876/1238) of indigenous women and 18% (36/197) of non-indigenous women delivered at home. Some 17% (247/1416) of women overall, and 33% (171/525) of those delivering in a health facility, reported an episiotomy during delivery. Among 171 women reporting an episiotomy in a health facility, 30% (52) also reported a perineal tear. Overall, 13% (190/1412) of women reported they had a perineal tear during delivery, 17% (86/515) of those delivering in a health facility and 12% (104/897) of those delivering at home. A quarter of the women had self-reported perineal trauma during their last delivery, 38% (196/511) of those delivering in a health facility and 18% (160/893) of those delivering at home. In bivariate analysis, indigenous ethnicity, home delivery, upright posture in labour, and delivery by a traditional midwife were associated with a lower risk of perineal trauma, while primiparas had a higher risk. In the final multivariate model, delivery by a traditional midwife was protective (ORa 0.41, 95%CIca 0.32-0.54) and primiparity was a risk factor (ORa 2.01, 95%CIca 1.5-2.68) for perineal trauma. Women suggested that fear of bad treatment and being cut made them unwilling to deliver in health facilities. CONCLUSIONS: The rate of perineal trauma among women giving birth in indigenous communities could be reduced by efforts to decrease the use of episiotomies in health facilities, and by opening a dialogue with traditional midwives to increase their interaction with formal health services.

Vasodilator Activity of Compounds Isolated from Plants Used in Mexican Traditional Medicine.

Arterial hypertension is one of the main risk factors in the development of cardiovascular diseases. Therefore, it is important to look for new drugs to treat hypertension. In this study, we carried out the screening of 19 compounds (triterpenes, diterpenes, sesquiterpenes, lignans, and flavonoids) isolated from 10 plants used in Mexican traditional medicine to determine whether they elicited vascular smooth muscle relaxation and, therefore, could represent novel anti-hypertension drug candidates. The vasorelaxant activity of these compounds was evaluated on the isolated rat aorta assay and the results obtained from this evaluation showed that three compounds induced a significant vasodilatory effect: meso-dihydroguaiaretic acid [half maximal effective concentration (EC50), 49.9 ± 11.2 µM; maximum effect (Emax), 99.8 ± 2.7%]; corosolic acid (EC50, 108.9 ± 6.7 µM; Emax, 96.4 ± 4.2%); and 5,8,4'-trihydroxy-3,7-dimethoxyflavone (EC50, 122.3 ± 7.6 µM; Emax, 99.5 ± 5.4%). Subsequently, involvement of the NO/cyclic guanosine monophosphate (cGMP) and H2S/ATP-sensitive potassium channel (KATP) pathways on the vasodilator activity of these compounds was assessed. The results derived from this analysis showed that the activation of both pathways contributes to the vasorelaxant effect of corosolic acid. On the other hand, the vasodilator effect of meso-dihydroguaiaretic acid and 5,8,4'-trihydroxy-3,7-dimethoxyflavone, partly involves stimulation of the NO/cGMP pathway. However, these compounds also showed an important endothelium-independent vasorelaxant effect, whose mechanism of action remains to be clarified. This study indicates that meso-dihydroguaiaretic acid, corosolic acid, and 5,8,4'-trihydroxy-3,7-dimethoxyflavone could be used as lead compounds for the synthesis of new derivatives with a higher potency to be developed as drugs for the prevention and treatment of cardiovascular diseases.

Periodo intergenésico: Revisión de la literature / Intergenesis period: Literature review

RESUMEN ANTECEDENTES: El período intergenésico es importante para la planificación de embarazos subsecuentes a partos, cesáreas y abortos. Actualmente existe falta de consenso en cuanto a las definiciones e importancia clínica de la duración del periodo intergenésico; por lo que se realiza esta revisión de la literatura para definir conceptos. MÉTODO: Se realizó una búsqueda bibliográfica en Pubmed y Medline, con periodo de búsqueda del 19992017, con el propósito de identificar publicaciones de relevancia relacionadas a periodo intergenésico. RESULTADOS: Entre los artículos seleccionados, se incluyeron de tipo revisión, originales y guías de práctica clínica. Se considera periodo intergenésico aquel que se encuentra entre la fecha del último evento obstétrico y el inicio del siguiente embarazo. Se sugiere como tiempo recomendado de espera para iniciar un siguiente embarazo mínimo 18 meses (Periodo intergenésico corto, PIC) y no más de 60 meses (Periodo intergenésico largo, PIL), para reducir el riesgo de eventos adversos maternos, perinatales y neonatales. Se debe enfatizar que aunque la dehiscencia de histerorrafia es una grave complicación del PIC menor a 6 meses posterior a una cesárea, no es su única complicación. De igual manera es importante tomar en cuenta el PIL durante la evaluación obstétrica, debido a su asociación con preeclampsia. CONCLUSIONES: Es relevante conocer la terminología adecuada en período intergenésico para evitar complicaciones asociadas a PIC como a PIL. Existe necesidad de estudios clínicos sobre período intergenésico que permitan conocer más consecuencias a corto y largo plazo en nuestra población y tomar medidas para mejorar el desenlace materno-fetal.

ABSTRACT BACKGROUND: Interpregnancy interval is a topic of importance when planning new pregnancies after previous vaginal delivery, cesarean section or abortion. There is currently a lack of consensus in terms of definitions and the clinical importance of interpregnancy interval length, which is the reason to perform a literature review to clarify concepts. METHODS: Published papers from 1999 to 2017 from PubMed/MEDLINE were searched with the purpose of identifying those related to interpregnancy interval. Review articles, original papers, and clinical guidelines in relation to short and long interpregnancy interval were considered. RESULTS: Interpregnancy interval is defined as the period between the last obstetric event and the beginning of the next pregnancy (last menstrual period). Recommended time to initiate the next pregnancy must be at least 18 months (short interpregnancy interval, SII) and no more than 60 months (long interpregnancy interval, LII) to reduce the risk of adverse maternal, perinatal and neonatal outcomes. It is important to emphasize that even though uterine scar dehiscence is a serious complication of SII less than 6 months after a cesarean section, it is not the only complication. It is important to consider LII during obstetric evaluation, due to its association with preeclampsia. CONCLUSION: It is clinically relevant to know the correct definitions of SII and LII to avoid their complications. There is also a need for clinical trials about interpregnancy interval within our population in order to better understand the consequences of SII and LII, thus taking the necessary measures to improve maternal and fetal outcomes.

In Vitro Inhibitory Activity of Acca sellowiana Fruit Extract on End Products of Advanced Glycation.

INTRODUCTION: Hyperglycemia plays an important role in the pathogenesis of diabetic complications, as it increases protein glycation, as well as the progressive accumulation of advanced glycation end products (AGEs), which are complex structures that produce fluorescence. The glycation reaction raises the levels of protein carbonyl, N ε-(carboxymethyl)lysine (CML), and fructosamine and decreases the level of thiol groups. METHODS: In the present study, the antiglycation activity was determined by fluorescence intensity using the bovine serum albumin (BSA)/glucose, CML method, and the level of fructosamine. The oxidation of proteins was determined by the carbonyl protein content and thiol groups. RESULTS: The results show that the hexane extract of Acca sellowiana (FOH) at different concentrations (0.30-5 mg/ml) significantly inhibited the formation of AGEs in the BSA/glucose model during the 4 weeks of the study. FOH reduced the levels of fructosamine and CML. Our results showed a significant effect of FOH in the prevention of oxidative damage of proteins, as well as an effect on the oxidation of thiol groups and carbonyl proteins. CONCLUSION: The present study indicates that FOH is effective in inhibiting the glycation of proteins in vitro, so it can prevent or ameliorate the chronic conditions of diabetes associated with the formation of AGEs.

meso-Dihydroguaiaretic acid derivatives with antibacterial and antimycobacterial activity.

Thirty-three meso-dihydroguaiaretic acid (meso-DGA) derivatives bearing esters, ethers, and amino-ethers were synthesized. All derivatives were tested against twelve drug-resistant clinical isolates of Gram-positive and Gram-negative bacteria, including sensitive (H37Rv) and multidrug-resistant Mycobacterium tuberculosis strains. Among the tested compounds, four esters (7, 11, 13, and 17), one ether (23), and three amino-ethers (30, 31, and 33) exhibited moderate activity against methicillin-resistant Staphylococcus aureus, whereas 30 and 31 showed better results than levofloxacin against vancomycin-resistant Enterococcus faecium. Additionally, nineteen meso-DGA derivatives displayed moderate to potent activity against M. tuberculosis H37Rv with minimum inhibitory concentration (MIC) values ranging from 3.125 to 50µg/mL. Seven meso-DGA derivatives bearing amino-ethers (26-31 and 33) exhibited the lowest MICs against M. tuberculosis H37Rv and G122 strains, with 31 being as potent as ethambutol (MICs of 3.125 and 6.25µg/mL). The presence of positively charged group precursors possessing steric and hydrophobic features (e.g. N-ethylpiperidine moieties in meso-31) resulted essential to significantly increase the antimycobacterial properties of parent meso-DGA as supported by the R-group pharmacophoric and field-based QSAR analyses. To investigate the safety profile of the antimycobacterial compounds, cytotoxicity on Vero cells was determined. The amino-ether 31 exhibited a selectivity index value of 23, which indicate it was more toxic to M. tuberculosis than to mammalian cells. Therefore, 31 can be considered as a promising antitubercular agent for further studies.

Transgenerational inheritance of neurobehavioral and physiological deficits from developmental exposure to benzo[a]pyrene in zebrafish.

Benzo[a]pyrene (B[a]P) is a well-known genotoxic polycylic aromatic compound whose toxicity is dependent on signaling via the aryl hydrocarbon receptor (AHR). It is unclear to what extent detrimental effects of B[a]P exposures might impact future generations and whether transgenerational effects might be AHR-dependent. This study examined the effects of developmental B[a]P exposure on 3 generations of zebrafish. Zebrafish embryos were exposed from 6 to 120h post fertilization (hpf) to 5 and 10µM B[a]P and raised in chemical-free water until adulthood (F0). Two generations were raised from F0 fish to evaluate transgenerational inheritance. Morphological, physiological and neurobehavioral parameters were measured at two life stages. Juveniles of the F0 and F2 exhibited hyper locomotor activity, decreased heartbeat and mitochondrial function. B[a]P exposure during development resulted in decreased global DNA methylation levels and generally reduced expression of DNA methyltransferases in wild type zebrafish, with the latter effect largely reversed in an AHR2-null background. Adults from the F0 B[a]P exposed lineage displayed social anxiety-like behavior. Adults in the F2 transgeneration manifested gender-specific increased body mass index (BMI), increased oxygen consumption and hyper-avoidance behavior. Exposure to benzo[a]pyrene during development resulted in transgenerational inheritance of neurobehavioral and physiological deficiencies. Indirect evidence suggested the potential for an AHR2-dependent epigenetic route.