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Background: Poor diet quality contributes to morbidity and mortality and affects environmental sustainability. The EAT-Lancet reference diet offers a healthy and sustainable solution. This study aimed to estimate the association between diet cost and dietary quality, measured with an EAT-Lancet Index., Methods: An EAT-Lancet index was adapted to assess adherence to this dietary pattern from 24-h recalls data from the 2012 and 2016 Mexican National Health and Nutrition Surveys (n = 14,242). Prices were obtained from the Consumer Price Index. We dichotomized cost at the median (into low- and high-cost) and compared the EAT-Lancet index scores. We also used multivariate linear regression models to explore the association between diet cost and diet quality., Results: Individuals consuming a low-cost diet had a higher EAT-Lancet score than those consuming a high-cost diet (20.3 vs. 19.4 from a possible scale of 0 to 42; p < 0.001) due to a lower intake of beef and lamb, pork, poultry, dairy, and added sugars. We found that for each one-point increase in the EAT-Lancet score, there was an average decrease of MXN$0.4 in the diet cost (p < 0.001). This association was only significant among low- and middle-SES individuals., Conclusions: Contrary to evidence from high-income countries, this study shows that in Mexico, adhering to the EAT-Lancet reference diet is associated with lower dietar costs, particularly in lower SES groups. These findings suggest the potential for broader implementation of healthier diets without increasing the financial burden., (© 2024. The Author(s).)

Purpose: Human papillomavirus (HPV) is a prevalent sexually transmitted infection responsible for many anogenital and oropharyngeal cancers. Dental care providers have the potential to influence vaccine uptake, yet little is known about how patients perceive their role in HPV education and prevention., Methods: Parents of adolescents aged 9 to 17 years (n = 375) were recruited from Valdeorras District Hospital (Galicia, Spain) to investigate parents' attitudes concerning the involvement of dental care providers in discussions related to HPV. A survey was distributed to the participants, and 343 (91.5%) were included in the analysis., Results: In general, nearly half of the parents reported feeling comfortable regarding discussing HPV with their dentist. Participants described more comfort with dentists than with dental hygienists. Parents' comfort levels were influenced by various social determinants of health, including education level, marital status, geographic origin, and child vaccination status (p > 0.05)., Conclusion: Parents reported varying comfort levels when discussing HPV and its vaccine with dental professionals, displaying a preference for dentists. Dental settings have the potential to promote vaccination, but the existence of ongoing barriers needs to be addressed., (© 2024 American Association of Public Health Dentistry.)

Background: Non-communicable diseases (NCDs) are the leading causes of mortality in Mexico. Factors contributing to NCDs-related deaths may vary across small geographic areas such as municipalities. We aimed to predict municipal-level factors associated with NCD mortality in Mexican adults from 2005 to 2021 using the small-area analysis (SSA) approach., Methods: We gathered data on population sociodemographic, access to healthcare services, and mortality records at the municipal-level from census and public institutions from 2005 to 2021. We identified municipal predictors of NCDs mortality rates (MR) using negative binomial regression models., Results: A total of 584,052 observations of Mexican adults were analyzed. The national expected NCDs MR per 100,000 inhabitants was 210.7 (95%CI: 196.1-226.7) in 2005 and increased to 322.4 (95%CI: 300.3-346.4) by 2021. Predictors of NCDs mortality (quintile 5 vs. quintile 1) included; indigeneity (IRR = 1.15, 95%CI: 1.12-1.19), poverty (IRR = 1.14, 95%CI: 1.13-1.15), affiliation with Mexican Social Security Institute (IRR = 1.11, 95%CI: 1.09-1.14), households with television (IRR = 1.14, 95%CI: 1.11-1.17), and high density of ultra-processed food, alcohol & tobacco retail stores (IRR = 1.15, 95%CI: 1.13-1.17). The greatest increases in MR were observed in municipalities from Oaxaca (>200% increments)., Conclusion: There was an overall increase in NCDs MR from 2005 to 2021, with a significant geographic variation among Mexican municipalities. The results of this study highlight the importance of identifying priority areas in the country that urgently require public policies focused on local factors associated with deaths from NCDs, such as the regulation of the ultra-processed food, alcohol & tobacco retail stores, and efforts to reduce social inequalities., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Garduño-Alanis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Since 2020 in Mexico, front-of-pack warning labels (FOPWL) have been implemented in processed products. Evidence supports warning labels allow consumers to identify unhealthy products. We aimed to evaluate the hypothetical impact of the FOPWL regulation on the Mexican population's intake of critical nutrients and energy, based on the replacement of food and beverages using 4 hypothetical scenarios which represented the phases of the regulation., Methods: Dietary data were collected using a standardized 24-h dietary recall from the 2016 Mexican National Health and Nutrition Survey (n = 4184). To evaluate the hypothetical impact of FOPWL, the nutritional content of critical nutrients in processed products was evaluated according to the Mexican Official Standard 051 (NOM-051). Then, we replaced products with several warning labels (WL) with those with a fewer number of them or with non-processed food. For the replacement, 4 hypothetical scenarios were established: scenario 1: the current consumption of the Mexican Population, scenario 2: the replacement during the first phase of the norm, scenario 3: the replacement in the second phase and scenario 4: the replacement in the last phase. We estimated the means, confidence intervals (CI 95%), and the mean percentage change of energy, saturated fat, trans-fat, added sugars, and sodium intake during the second, third, and the fourth scenarios., Results: According to the norm, in the second scenario, the majority of the products presented a label for energy (52.6%) whereas in the third (56.4%) and fourth (61.2%) scenarios were for sodium. In contrast, trans-fat was the least labeled nutrient in all the scenarios (from 2.1 to 4.1%). In the fourth scenario, we observed a reduction of the intake of energy intake to 15.4% as well as saturated fat (- 20%, CI 95% - 18.4; - 21.6), trans-fat (- 8.2%, CI 95% - 6.4; - 10.1) and sodium (- 12.7%, CI 95% - 11.3; - 14.1). The most important reduction was observed for added sugars intake (until - 54.1%, CI 95% - 51; - 57.1)., Conclusions: FOPWL could be an effective strategy to decrease energy consumption and nutrients of concern. If consumers use the FOPWL, it would be an important change in critical nutrients intake. These results support that FOPWL might help the Mexican population to choose healthier nutrition alternatives., (© 2023. The Author(s).)

Adolescents and young people are particularly vulnerable to contracting STIs, including HSV-2; furthermore, vaginal shedding of HSV-2 during pregnancy can cause vertical transmission and neonatal herpes. To evaluate the seroprevalence of HSV-2 and vaginal HSV-2 shedding in adolescent and young pregnant women, a cross-sectional study was carried out in 496 pregnant women-adolescents and young women. Venous blood and vaginal exudate samples were taken. The seroprevalence of HSV-2 was determined by ELISA and Western blot. Vaginal HSV-2 shedding was assessed by qPCR of the HSV-2 UL30 gene. The seroprevalence of HSV-2 in the study population was 8.5% (95% CI 6-11), of which 38.1% had vaginal HSV-2 shedding (95% CI 22-53). Young women presented a higher seroprevalence of HSV-2 (12.1%) than adolescents (4.3%), OR = 3.4, 95% CI 1.59-7.23. Frequent alcohol consumption was significantly associated with HSV-2 seroprevalence, OR = 2.9, 95% CI 1.27-6.99. Vaginal HSV-2 shedding is highest in the third trimester of pregnancy, but this difference is not significant. The seroprevalence of HSV-2 in adolescents and young women is similar to that previously reported in other studies. However, the proportion of women with vaginal shedding of HSV-2 is higher during the third trimester of pregnancy, increasing the risk of vertical transmission.

Obesity is among the most complex public health challenges, particularly in Latin America, where obesity rates have increased faster than in any other region. Many countries have proposed or enacted comprehensive policies to promote adequate diet and physical activity under a structural framework. We summarize articles discussing the scope and impact of recently implemented obesity-related interventions in the light of a structural response framework. Overall, we find that: (1) market-based food interventions, including taxes on junk food, nutrition labelling, and marketing restrictions, decrease the consumption of targeted foods, (2) programs directly providing healthy foods are effective in reducing obesity, and (3) the construction of public areas for recreation increases the average frequency of physical activity. Although obesity-related interventions in the region have somewhat improved health behaviours, obesity prevalence remains on an upward trend. We discuss some opportunities to continue tackling the obesity epidemic in LATAM under a structural framework., Competing Interests: None of the authors have a conflict of interests of any type with respect to this manuscript to declare. The opinions and conclusions expressed herein are solely those of the authors and should not be construed., (© 2023 The Authors.)

Iron absorption is a complex and highly controlled process where DMT1 transports nonheme iron through the brush-border membrane of enterocytes to the cytoplasm but does not transport alkaline-earth metals such as calcium. However, it has been proposed that high concentrations of calcium in the diet could reduce iron bioavailability. In this work, we investigate the effect of intracellular and extracellular calcium on iron uptake by Caco-2 cells, as determined by calcein fluorescence quenching. We found that extracellular calcium inhibits iron uptake by Caco-2 cells in a concentration-dependent manner. Chelation of intracellular calcium with BAPTA did not affect iron uptake, which indicates that the inhibitory effect of calcium is not exerted through intracellular calcium signaling. Kinetic studies performed, provided evidence that calcium acts as a reversible noncompetitive inhibitor of the iron transport activity of DMT1. Based on these experimental results, a mathematical model was developed that considers the dynamics of noncompetitive inhibition using a four-state mechanism to describe the inhibitory effect of calcium on the DMT1 iron transport process in intestinal cells. The model accurately predicts the calcein fluorescence quenching dynamics observed experimentally after an iron challenge. Therefore, the proposed model structure is capable of representing the inhibitory effect of extracellular calcium on DMT1-mediated iron entry into the cLIP of Caco-2 cells. Considering the range of calcium concentrations that can inhibit iron uptake, the possible inhibition of dietary calcium on intestinal iron uptake is discussed.

Flavonoids are naturally occurring compounds widely distributed in the Citrus genus. These natural compounds have many health benefits, mainly for metabolic and cardiovascular diseases. In fact, some these compounds are components of drug products with approved indications for peripheral vascular insufficiency and hemorrhoids. However, information on pharmacological effects of these compounds remains disperse and there is scarce comprehensive analysis of whole data and evidence. These kinds of evidence analyses could be necessary in drug design and the development of novel and innovate drug products in diabetes and hypertension. We aimed to systematically search for evidence on the efficacy of citroflavonoids in diabetes and hypertension in in vivo models. We searched four literature databases based on a PICO strategy. After database curation, twenty-nine articles were retrieved to analyze experimental data. There was high heterogeneity in both outcomes and methodology. Naringenin and hesperetin derivates were the most studied citroflavonoids in both experimental models. More investigation is still needed to determine its potential for drug design and development.

Lung allocation in the US changed nearly 15 years ago from time accrued on the waiting list to disease severity and likelihood of posttransplant survival, represented by the lung allocation score (LAS). Notably, the risk of death within a year plays a stronger role on the score calculation than posttransplant survival. While this change was associated with the intended decrease in waitlist mortality (most recently reported at 14.6%), it was predictable that transplant teams would have to care for increasingly older and complex candidates and recipients. This urgency-based allocation also led centers to routinely consider transplanting patients with higher acuity, often hospitalized and, not infrequently, in the intensive care unit (ICU). According to the Scientific Registry for Transplant Recipients, from 2009 to 2019, the proportion of lung recipients hospitalized and those admitted to the ICU at the time of transplant increased from 18.9% to 26.8% and from 9.2% to 16.5%, respectively.., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: Drug utilization research (DUR) contributes to inform policymaking and to strengthen health systems. The availability of data sources is the first step for conducting DUR. However, documents that systematize these data sources in Latin American (LatAm) countries are not known. We compiled the potential data sources for DUR in the LatAm region., Methods: A network of DUR experts from nine LatAm countries was assembled and experts conducted: (i) a website search of the government, academic, and private health institutions; (ii) screening of eligible data sources, and (iii) liaising with national experts in pharmacoepidemiology (via an online survey). The data sources were characterized by accessibility, geographic granularity, setting, sector of the data, sources and type of the data. Descriptive analyses were performed., Results: We identified 125 data sources for DUR in nine LatAm countries. Thirty-eight (30%) of them were publicly and conveniently available; 89 (71%) were accessible with limitations, and 18 (14%) were not accessible or lacked clear rules for data access. From the 125 data sources, 76 (61%) were from the public sector only; 46 (37%) were from pharmacy records; 43 (34%) came from ambulatory settings and; 85 (68%) gave access to individual patient-level data., Conclusions: Although multiple sources for DUR are available in LatAm countries, the accessibility is a major challenge. The procedures for accessing DUR data should be transparent, feasible, affordable, and protocol-driven. This inventory could permit a comparison of drug utilization between countries identifying potential medication-related problems that need further exploration., (© 2021 John Wiley & Sons Ltd.)

This study was performed to evaluate and compare the pharmacokinetic parameters between two dosage formulations of hesperidin and naringenin: mixture and tablet. Our objective was to determine that the flavonoid tablet does not significantly modify the pharmacokinetic parameters compared with the mixture. For this study, we administered 161 mg/kg of either mixture (Mix-160) or tablet composed of hesperidin and by intragastric administration. Blood microsamples were collected from tail vein up to 24 h. Serum flavonoid extraction was performed by solid phase extraction and analyzed by LC-MS/MS of triple quadrupole (QqQ). Serum concentration vs. time plot showed that data fitted for a first-order model. The pharmacokinetic parameters were calculated by a noncompartmental model. The results showed that the absorption constant is higher than the elimination constant. The first concentration was found at five minutes, and minimal concentration at 24 h after administration, suggesting a enterohepatic recirculation phenomena and regulation of liver cytochromes' activity. We did not find meaningful differences between the pharmacokinetic parameters of both samples. We concluded that tablet form did not interfere with the bioavailability of hesperidin and naringenin, and it could be a suitable candidate for developing a drug product.

It is unknown whether some donor specific antibodies (DSA) can be crossed at the time of lung transplant without desensitization or augmented induction immunosuppression. This study assessed whether crossing low-level pre-transplant DSA (defined as mean fluorescence intensity [MFI] 1000-6000) without augmented immunosuppression is associated with worse retransplant-free or chronic lung allograft dysfunction (CLAD)-free survival. Of the 458 included recipients, low-level pre-transplant DSA was crossed in 39 (8.6%) patients. The median follow-up time was 2.2 years. There were 15 (38.5%) patients with Class I DSA and 24 (61.5%) with Class II DSA. There was no difference in adjusted overall retransplant-free survival between recipients where pre-transplant DSA was and was not crossed (HR: .98 [95% CI = .49-1.99], P = .96). There was also no difference in CLAD-free survival (HR: .71 [95% CI = .38-1.33], P = .28). There was no difference in Grade 3 PGD at 72 h (OR: 1.13 [95% CI = .52-2.48], P = .75) or definite or probable AMR (HR: 2.22 [95% CI = .64-7.61], P = .21). Lung transplantation in the presence of low-level DSA without planned augmented immunosuppression is not associated with worse overall or CLAD-free survival among recipients with intermediate-term follow-up., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Wolbachia are endosymbiont bacteria known to infect arthropods causing different effects, such as cytoplasmic incompatibility and pathogen blocking in Aedes aegypti. Although several Wolbachia strains have been studied, there is little knowledge regarding the relationship between this bacterium and their hosts, particularly on their obligate endosymbiont nature and its pathogen blocking ability. Motivated by the potential applications on disease control, we developed a genome-scale model of two Wolbachia strains: w Mel and the strongest Dengue blocking strain known to date: w MelPop. The obtained metabolic reconstructions exhibit an energy metabolism relying mainly on amino acids and lipid transport to support cell growth that is consistent with altered lipid and cholesterol metabolism in Wolbachia -infected mosquitoes. The obtained metabolic reconstruction was then coupled with a reconstructed mosquito model to retrieve a symbiotic genome-scale model accounting for 1,636 genes and 6,408 reactions of the Aedes aegypti- Wolbachia interaction system. Simulation of an arboviral infection in the obtained novel symbiotic model represents a metabolic scenario characterized by pathogen blocking in higher titer Wolbachia strains, showing that pathogen blocking by Wolbachia infection is consistent with competition for lipid and amino acid resources between arbovirus and this endosymbiotic bacteria. IMPORTANCE Arboviral diseases such as Zika and Dengue have been on the rise mainly due to climate change, and the development of new treatments and strategies to limit their spreading is needed. The use of Wolbachia as an approach for disease control has motivated new research related to the characterization of the mechanisms that underlie its pathogen-blocking properties. In this work, we propose a new approach for studying the metabolic interactions between Aedes aegypti and Wolbachia using genome-scale models, finding that pathogen blocking is mainly influenced by competition for the resources required for Wolbachia and viral replication.

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC 50 of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD 50 value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD 50 was LD 50 > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.

This work applied environmental isotope techniques to validate the results of previous studies on recharge sources in a rural area in central Chile (34.3° S and 71.3° W) and discern the origin of nitrate contamination in wells. Stream water and groundwater samples were taken during three surveys, two during spring snowmelt and one in low-water conditions. Chemical analyses included major cations and anions, isotope analyses included 18 O-H 2 O; 2 H-H 2 0; 3 H-H 2 0; 18 O-NO 3 - and 15 N-NO 3 - . The stable isotope data show that surface water and deep groundwater present depleted isotope values associated with recharge from the Andes Mountains and that shallow groundwater has more enriched isotope values that reflect the contribution of local recharge from rainwater infiltration. Depleted isotope values observed in shallow groundwater show the effect of recirculated river water used for irrigation. These results are consistent with the conceptual groundwater model developed in previous studies. Some wells have nitrate concentrations above the allowable limit for drinking water. The stable nitrogen isotopes indicate that nitrate is associated mainly with urea and ammoniacal fertilizers, and nitrate is attenuated by denitrification. The results of this study are relevant to improving management of groundwater resources used for drinking water.

Objective: This work describes the vasorelaxant and antihypertensive effects and the mechanism of action on vascular smooth muscle cells of Nibethione, a synthetic thiazolidinedione derivative. Additionally, evidence of its cytotoxicity is assessed., Methods: Nibethione (NB) was synthesized, and its vasorelaxant effect and mechanism of action were assessed through ex vivo experiments. Molecular docking studies were used to predict the mode of interaction with L-type Ca 2+ channel, and in vivo antihypertensive activity was assayed on spontaneously hypertensive rats (SHR). The cytotoxicity potential was evaluated in porcine aortic endothelial cells (PAECs) from primary explants., Key Findings: Nibethione vasorelaxant effect was efficient on KCl (80 mm) and NE-contraction. This effect was deleteriously modified in the presence of potassium channel block drugs, while the maximal contraction induced with NE was significantly decreased by NB; the CaCl 2 -induced contraction was abolished entirely. In vivo experiments showed that NB decreased diastolic blood pressure in 20.3 % after its administration on SHR. The molecular docking showed that NB blocks L-type Ca 2+ channel, and in vitro tests showed that NB did not produce cytotoxic activity on PAECs (IC 50 >1000 µm)., Conclusions: Nibethione showed in vivo antihypertensive and ex vivo vasorelaxant effects with implication of voltage-dependent L-type Ca 2+ channel blocking, and this may contribute to the research of novel antihypertensive drugs., (© 2020 Royal Pharmaceutical Society.)

Type of metal and metal-oxide NPs added to modify Thin-Film Composites Reverse Osmosis Membranes (TFC-RO) can alter their anti-biofouling properties by changing the dissolution process. The development of a mathematical model can facilitate the selection of these NPs. This work consists of a mathematical and experimental methodology to understand copper-based NPs dissolution of three copper species incorporated into TFC-RO membranes: Cu-NPs, CuO-NPs and Cu-Oligomer complexes formed in situ during the polymerization process. Biocidal capacity of copper species into the membrane was evaluated using colony forming unit method (CFU) over E. coli . In addition, copper ion release kinetics for both NPs and modified membranes were determined. A model based on the shrinking core model (SCM) was validated and applied to determine the limiting rate step in the dissolution process and simulate the ion release kinetics. Fitted curves reached a good adjustment with the experimental data, demonstrating the SCM can be applied to predict ion release process for copper-based NPs in suspension and the modified membranes. All membranes reached similar inhibition rate >50%, however, differences in the dissolution level of copper-based NPs in membrane were noted, suggesting a dual-type effect that defined the copper toxicity into the membrane, associated to the dissolution capacity and ROS production.

To address the high prevalence of overweight and obesity in Mexico, an eight percent ad valorem excise tax on non-essential energy-dense foods came into effect on 1 January 2014. This paper estimates price changes after the tax implementation among the top four food categories and by leading vs. non-leading firms using purchase information from over 6000 urban households in the 2012-2015 Nielsen Mexico Consumer Panel. We create product-city-month specific prices that correct for potential biases associated with household and retailer characteristics. Using these corrected prices, we conduct before and after quasi-experimental analyses and find that price increases were larger than eight percent for cookies but were less than eight percent for ready-to-eat cereals, salty snacks, and pre-packaged sweet bread. For the latter food group, event-study analyses on the gradual price change over time suggest that price changes might be the result of an increasing price trend rather than the tax implementation. Firm-level analyses mostly show that price increases by the leading firms were larger than the overall increase at the food market level, helping explain variability in post-tax declines in food purchases as reported in other research. We also find that price changes are generally underestimated when we do not correct prices for biases associated with households and retailers. These results improve our understanding of the mechanisms behind heterogeneous changes in purchases after the tax implementation. Additionally, these results can assist policymakers when designing or improving taxes on non-essential energy-dense foods at a time when these policy options are high on the agenda in many places.

Wolbachia are alpha-proteobacteria known to infect arthropods, which are of interest for disease control since they have been associated with improved resistance to viral infection. Although several genomes for different strains have been sequenced, there is little knowledge regarding the relationship between this bacterium and their hosts, particularly on their dependency for survival. Motivated by the potential applications on disease control, we developed genome-scale models of four Wolbachia strains known to infect arthropods: wAlbB (Aedes albopictus), wVitA (Nasonia vitripennis), wMel and wMelPop (Drosophila melanogaster). The obtained metabolic reconstructions exhibit a metabolism relying mainly on amino acids for energy production and biomass synthesis. A gap analysis was performed to detect metabolic candidates which could explain the endosymbiotic nature of this bacterium, finding that amino acids, requirements for ubiquinone precursors and provisioning of metabolites such as riboflavin could play a crucial role in this relationship. This work provides a systems biology perspective for studying the relationship of Wolbachia with its host and the development of new approaches for control of the spread of arboviral diseases. This approach, where metabolic gaps are key objects of study instead of just additions to complete a model, could be applied to other endosymbiotic bacteria of interest., Competing Interests: The authors have declared that no competing interests exist.

Iron is essential for the normal development of cellular processes. This metal has a high redox potential that can damage cells and its overload or deficiency is related to several diseases, therefore it is crucial for its absorption to be highly regulated. A fast-response regulatory mechanism has been reported known as mucosal block, which allows to regulate iron absorption after an initial iron challenge. In this mechanism, the internalization of the DMT1 transporters in enterocytes would be a key factor. Two phenomenological models are proposed for the iron absorption process: DMT1's binary switching mechanism model and DMT1's swinging-mechanism model, which represent the absorption mechanism for iron uptake in intestinal cells. The first model considers mutually excluding processes for endocytosis and exocytosis of DMT1. The second model considers a Ball's oscillator to represent the oscillatory behavior of DMT1's internalization. Both models are capable of capturing the kinetics of iron absorption and represent empirical observations, but the DMT1's swinging-mechanism model exhibits a better correlation with experimental data and is able to capture the regulatory phenomenon of mucosal block. The DMT1 swinging-mechanism model is the first phenomenological model reported to effectively represent the complexity of the iron absorption process, as it can predict the behavior of iron absorption fluxes after challenging cells with an initial dose of iron, and the reduction in iron uptake observed as a result of mucosal block after a second iron dose., Competing Interests: The authors have declared that no competing interests exist.

Introduction and Objective: The risk of intervention due to urogenital prolapse in a woman's life is 11.1%. Recurrences after classic surgery reach up to 38%. With the aim of improving these results, transvaginal mesh kits are used. The purpose of the study is to describe the results of efficacy and long-term safety of vaginal prolapse surgery with polypropylene mesh, assess subjective symptoms before and after surgery and the level of satisfaction., Patients and Methods: A descriptive, retrospective study of 58 women with symptomatic genital prolapses operated with polypropylene mesh between September / 2011-November / 2016. Mean age: 66.53 years, 98.27% menopausal women, 77.59% overweight/obesity, 29.31% with previous gynaecological surgery and 55.17% with combined prolapse. 46 Elevate anterior and 12 posterior were inserted. The mean follow-up period was 34.02 months. The PFDI questionnaire was used pre and post-surgery, as well as the satisfaction questionnaire., Results: Healing rate of 91.38%. Recurrences were associated with a higher BMI and with background of recurrence of previous surgery. Mean length of stay: 2.5 days. 70.69% did not need analgesia at discharge. Clavien-Dindo complications: 1 type I (urinary retention), 5 type II (urinary tract infection) and 1 type IIIa (erosion). De novo stress urinary incontinence occurred in 3.44%, while de novo dyspareunia 14.28%. 89.36% patients improved subjective symptoms, and 95.92% were satisfied., Conclusion: This surgery achieves high healing rates, with few complications, improvement of subjective symptoms and high level of satisfaction of the patients., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Flavonoids are naturally occurring compounds that show health benefits on the liver. However, there is little investigation about identification and evaluation of new flavonoid-containing drugs for cholestatic liver disease, one of the most common liver illnesses. We aimed to a systematic search regarding efficacy of flavonoids for treatment of cholestatic liver disease, and then evaluate naringenin (NG) as representative flavonoid in an obstructive cholestasis model. We searched for information of experimental and clinical studies in four major databases without time and language limits. Intervention was defined as any flavonoid derivate compared with other flavonoid, placebo, or without comparator. In addition, we evaluated NG on a bile duct-ligated model in order to contribute evidence of its actions. Eleven experimental reports that support the efficacy of flavonoids in cholestatic liver disease were identified. However, there was no homogeneity in efficacy endpoints evaluated and methodology. On the other hand, NG showed beneficial effects by improving specific metabolic (cholesterol and lipoproteins) and liver damage (bilirubin and alkaline phosphatase) biomarkers. The review lacks homogeneous evidence about efficacy of flavonoids in experimental settings, and is susceptible to risk for bias. NG only showed improvements in specific disease biomarkers. More investigation is still needed to determine its potential for drug development.

Leishmaniasis is a neglected tropical disease that currently affects 12 million people, and over 1 billion people are at risk of infection. Current chemotherapeutic approaches used to treat this disease are unsatisfactory, and the limitations of these drugs highlight the necessity to develop treatments with improved efficacy and safety. To inform the rational design and development of more efficient therapies, the present study reports a chemoinformatic approach using the ChEMBL database to retrieve benzimidazole as a target scaffold. Our analysis revealed that a limited number of studies had investigated the antileishmanial effects of benzimidazoles. Among this limited number, L. major was the species most commonly used to evaluate the antileishmanial effects of these compounds, whereas L. amazonensis and L. braziliensis were used least often in the reported studies. The antileishmanial activities of benzimidazole derivatives were notably variable, a fact that may depend on the substitution pattern of the scaffold. In addition, we investigated the effects of a benzimidazole derivative on promastigotes and amastigotes of L. infantum and L. amazonensis using a novel fluorometric method. Significant antileishmanial effects were observed on both species, with L. amazonensis being the most sensitive. To the best of our knowledge, this chemoinformatic analysis represents the first attempt to determine the relevance of benzimidazole scaffolds for antileishmanial drug discovery using the ChEMBL database. The present findings will provide relevant information for future structure-activity relationship studies and for the investigation of benzimidazole-derived drugs as potential treatments for leishmaniasis.

Where people shop for food is often linked to the healthiness of food purchases. In Mexico, no research has examined the connection between where people shop, what they buy, and their socioeconomic status (SES). Mexico's sugary beverage and junk food taxes have made households decrease purchases of taxed products. However, whether households have changed where they shop is unknown. To address this gap, we use a repeated cross-sectional analysis of household packaged food and beverage purchases from the Nielsen Mexico Consumer Panel Survey from 2012 to 2015 ( n > 5500 households). We examine changes in the volume of the purchase of taxed and untaxed products from different store-types (i.e., convenience stores, supermarkets, traditional retailers, wholesalers, home water-delivery, and others) by SES using multivariate linear regression models. Results show that high-SES households purchased more foods and beverages at all store-types except for low-SES who purchased the most foods and taxed beverages at traditional retailers. Purchases of taxed foods and beverages from traditional retailers significantly decreased for low-SES and middle-SES households and from supermarkets for middle-SES and high-SES households. Purchases of untaxed beverages from wholesalers significantly increased for middle-SES households and from convenience stores for high-SES households. Our findings suggest that consumers choose different stores to purchase beverages than to purchase foods and that taxes may have differentially affected each store-type.

Background: Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx., Methods: The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival. Multivariate Cox regression models were used to assess the effect of recipient and donor characteristics on survival., Results: Of the patients who underwent ReTx, median survival was 2 years. Predictors of worse survival include recipient age between 50 and 60 years (relative risk, 4.3; p = 0.02) or older than 60 years (relative risk, 10.2; p < 0.001), and time to ReTx of less than 2 years (relative risk, 3.8; p = 0.01). ReTx for bronchiolitis obliterans syndrome had longer median survival than for restrictive chronic lung allograft dysfunction (2.7 years vs 0.9 years; p = 0.055). Overall survival of ReTx patients after initiation of the lung allocation score was not significantly different (p = 0.21)., Conclusions: Lung ReTx outcomes are significantly worse than for primary transplantation but may be appropriate in well-selected patients with certain diagnoses. Lung ReTx in patients older than 50 years or within 2 years of primary lung transplantation was associated with decreased survival. Further work is warranted to identify patients who benefit most from ReTx., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Case Presentaion: A 42-year-old woman with mixed connective tissue disease-associated interstitial lung disease underwent bilateral lung transplantation. She had an uneventful surgery and was extubated 3 h later. Induction immunosuppression therapy included methylprednisolone 500 mg intraoperatively, basiliximab (anti-IL-2 monoclonal antibody) on days 0 and 4 after transplantation, and methylprednisolone 125 mg intravenously bid for 2 days following surgery. Maintenance immunosuppression therapy consisted of prednisone 20 mg daily, mycophenolate mofetil 750 mg bid, and enteral tacrolimus 0.5 mg bid. Both the donor and the recipient were seropositive for cytomegalovirus. Infectious disease prophylaxis consisted of valganciclovir, trimethoprim-sulfamethoxazole, and voriconazole., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Iron is a trace metal, key for the development of living organisms. Its absorption process is complex and highly regulated at the transcriptional, translational and systemic levels. Recently, the internalization of the DMT1 transporter has been proposed as an additional regulatory mechanism at the intestinal level, associated to the mucosal block phenomenon. The short-term effect of iron exposure in apical uptake and initial absorption rates was studied in Caco-2 cells at different apical iron concentrations, using both an experimental approach and a mathematical modeling framework. This is the first report of short-term studies for this system. A non-linear behavior in the apical uptake dynamics was observed, which does not follow the classic saturation dynamics of traditional biochemical models. We propose a method for developing mathematical models for complex systems, based on a genetic programming algorithm. The algorithm is aimed at obtaining models with a high predictive capacity, and considers an additional parameter fitting stage and an additional Jackknife stage for estimating the generalization error. We developed a model for the iron uptake system with a higher predictive capacity than classic biochemical models. This was observed both with the apical uptake dataset used for generating the model and with an independent initial rates dataset used to test the predictive capacity of the model. The model obtained is a function of time and the initial apical iron concentration, with a linear component that captures the global tendency of the system, and a non-linear component that can be associated to the movement of DMT1 transporters. The model presented in this paper allows the detailed analysis, interpretation of experimental data, and identification of key relevant components for this complex biological process. This general method holds great potential for application to the elucidation of biological mechanisms and their key components in other complex systems., Competing Interests: The authors have declared that no competing interests exist.

A 48-year-old African-American male subject presented with progressive fatigue, jaundice, and new-onset leukopenia 12 weeks after undergoing bilateral lung transplantation for advanced pulmonary sarcoidosis. His transplant surgery and immediate posttransplantation course were uneventful. Induction immunosuppression included methylprednisolone 500 mg intraoperatively and basiliximab (anti-IL-2 monoclonal antibody) on days 0 and 4 after transplantation. His maintenance immunosuppression posttransplantation was prednisone 20 mg daily, tacrolimus with target tacrolimus levels 10 to 15 ng/mL, and mycophenolate mofetil 750 mg twice daily. Both the donor and recipient were seropositive for cytomegalovirus and Epstein-Barr virus. Infectious disease prophylaxis consisted of valganciclovir, trimethoprim/sulfamethoxazole, and voriconazole. Results of the surveillance bronchoscopy conducted after the lung transplant were negative for acute cellular rejection or infection at 4 and 12 weeks' posttransplantation. Findings on spirometry had continuously improved since transplantation., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

In 2014 an excise tax to non-alcoholic sweetened beverages (SSB) was implemented in Mexico. The objective of this paper is to study whether and to what degree these taxes passed-through onto SSB prices in urban areas overall and by region, type of beverage and package size. Prices were obtained from the National Institute of Statistics and Geography from 2011 to 2014. We applied a pre-post quasi-experimental approach using fixed effects models. In sensitivity analysis we applied other model specifications to test the robustness of the findings and we also present weighted estimations based on household purchases. The dependent variables are real prices of a specific beverage category; the main independent variables are dummies for each month of 2014, and the models adjust for time trends and seasonality. Results suggest that the SSB tax passed along to consumers for all SSBs and we found overshifting for the carbonated SSBs. A greater effect is seen among the small package sizes, and we see heterogeneous effects by region. Estimating the effect of the tax on prices is important to understand the potential effect on consumption.

A large and growing body of scientific evidence demonstrates that sugar drinks are harmful to health. Intake of sugar-sweetened beverages (SSB) is a risk factor for obesity and type 2 diabetes. Mexico has one of the largest per capita consumption of soft drinks worldwide and high rates of obesity and diabetes. Fiscal approaches such as taxation have been recommended as a public health policy to reduce SSB consumption. We estimated an almost ideal demand system with linear approximation for beverages and high-energy food by simultaneous equations and derived the own and cross price elasticities for soft drinks and for all SSB (soft drinks, fruit juices, fruit drinks, flavored water and energy drinks). Models were stratified by income quintile and marginality index at the municipality level. Price elasticity for soft drinks was -1.06 and -1.16 for SSB, i.e., a 10% price increase was associated with a decrease in quantity consumed of soft drinks by 10.6% and 11.6% for SSB. A price increase in soft drinks is associated with larger quantity consumed of water, milk, snacks and sugar and a decrease in the consumption of other SSB, candies and traditional snacks. The same was found for SSB except that an increase in price of SSB was associated with a decrease in snacks. Higher elasticities were found among households living in rural areas (for soft drinks), in more marginalized areas and with lower income. Implementation of a tax to soft drinks or to SSB could decrease consumption particularly among the poor. Substitutions and complementarities with other food and beverages should be evaluated to assess the potential impact on total calories consumed., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Recent evidence shows that iron induces the endocytosis of the iron transporter dimetal transporter 1 (DMT1) during intestinal absorption. We, and others, have proposed that iron-induced DMT1 internalization underlies the mucosal block phenomena, a regulatory response that downregulates intestinal iron uptake after a large oral dose of iron. In this work, we investigated the participation of reactive oxygen species (ROS) in the establishment of this response. By means of selective surface protein biotinylation of polarized Caco-2 cells, we determined the kinetics of DMT1 internalization from the apical membrane after an iron challenge. The initial decrease in DMT1 levels in the apical membrane induced by iron was followed at later times by increased levels of DMT1. Addition of Fe(2+), but not of Cd(2+), Zn(2+), Cu(2+), or Cu(1+), induced the production of intracellular ROS, as detected by 2',7'-dichlorofluorescein (DCF) fluorescence. Preincubation with the antioxidant N-acetyl-l-cysteine (NAC) resulted in increased DMT1 at the apical membrane before and after addition of iron. Similarly, preincubation with the hydroxyl radical scavenger dimethyl sulfoxide (DMSO) resulted in the enhanced presence of DMT1 at the apical membrane. The decrease of DMT1 levels at the apical membrane induced by iron was associated with decreased iron uptake rates. A kinetic mathematical model based on operational rate constants of DMT1 endocytosis and exocytosis is proposed. The model qualitatively captures the experimental observations and accurately describes the effect of iron, NAC, and DMSO on the apical distribution of DMT1. Taken together, our data suggest that iron uptake induces the production of ROS, which modify DMT1 endocytic cycling, thus changing the iron transport activity at the apical membrane., (Copyright © 2015 the American Physiological Society.)

The increasing difference between the number of patients in waiting lists for liver transplantation and the number of available donors has generated a great interest in the use of non-ideal organs, like grafts obtained from cardiac death donors (DCD). However, the extreme sensibility to ischemia of these livers results in a low utilization rate and a high percentage of post-transplant complications and re-transplantation. Normothermic perfusion machines (NMP) emerged as an alternative that tries to maintain the viability of the organ and even to improve its function. This review focuses on current results of DCD liver transplantation and on the role that NMP may have in this field., (Copyright © 2015 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.)

Two of the possible catalytic mechanisms for neurotransmitter oxidative deamination by monoamine oxidase B (MAO B), namely, polar nucleophilic and hydride transfer, were addressed in order to comprehend the nature of their rate-determining step. The Quantum Chemical Cluster Approach was used to obtain transition states of MAO B complexed with phenylethylamine (PEA), benzylamine (BA), and p-nitrobenzylamine (NBA). The choice of these amines relies on their importance to address MAO B catalytic mechanisms so as to help us to answer questions such as why BA is a better substrate than NBA or how para-substitution affects substrate's reactivity. Transition states were later validated by comparison with the experimental free energy barriers. From a theoretical point of view, and according to the our reported transition states, their calculated barriers and structural and orbital differences obtained by us among these compounds, we propose that good substrates such as BA and PEA might follow the hydride transfer pathway while poor substrates such as NBA prefer the polar nucleophilic mechanism, which might suggest that MAO B can act by both mechanisms. The low free energy barriers for BA and PEA reflect the preference that MAO B has for hydride transfer over the polar nucleophilic mechanism when catalyzing the oxidative deamination of neurotransmitters.

A 41-year-old Hispanic woman with a 20 pack-year smoking history presented with worsening shortness of breath on exertion that gradually started 2 years ago, then significantly deteriorated over the last 4 months. She was diagnosed with COPD 2 months prior to her presentation and started on treatment with fluticasone propionate and albuterol. Her medical history was relevant for undifferentiated connective tissue disorder diagnosed 5 years prior due to a positive antinuclear antibody test, arthralgia, recurrent urticarial skin rash, peripheral neuropathy, abdominal pain, and diffuse body swelling. She was started on treatment with prednisone and azathioprine at the time and had substantial improvement in the occurrence of her urticaria. She also had a history of recurrent laryngeal edema of unclear etiology. She had no history of IV drug abuse, no exposure to animals, was not sexually active, and had no recent travel outside of Florida. There was no significant family history of lung diseases.

A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogenated inhibitors. Our results show that chloro, bromo and iodo derivatives have progressively narrower distributions of calculated geometries, which reflects the order of affinity I > Br > Cl, in agreement with the IC50 values. Graphs for the Cl, Br and I analogs show stable interactions between the halogen atom and the Gly61 carbonyl oxygen of the enzyme. The halogen-oxygen distance is close to or less than the sum of the van der Waals radii; the C-X···O angle is about 170°; and the X···O=C angle approaches 120°, as expected for halogen bond formation. In the case of the iodo-substituted analogs, these effects are enhanced by introduction of a fluorine atom on the inhibitors' halogen-bonding phenyl ring, indicating that the electron withdrawing group enlarges the σ-hole, resulting in improved halogen bonding properties.

Trauma to the mouth involves not only the teeth but also the dental pulp, the periodontal ligament, bone, gingiva and other associated structures. There are many different types of injuries with varying severity in each case and often more than one injury to a tooth at the same time. Hence, there are many different potential responses of the pulp, peri-radicular and soft tissues following trauma. The responses of the different tissues are inter-related and dependent on each other, which results in many potential consequences of trauma to the teeth. It is imperative that dentists have a thorough understanding of the possible tissue responses so appropriate treatment can be provided to minimise the consequences of trauma. The five main strategies to reduce these consequences are to: 1) perform a thorough examination and accurate diagnosis to identify all injuries and to assess the likely healing responses; 2) reposition and stabilise the teeth and bones to provide optimum conditions for healing; 3) carefully manage soft tissues to help healing; 4) commence root canal treatment immediately in specific situations to prevent external inflammatory resorption; and 5) follow-up and review all traumatised teeth to identify and manage any adverse consequences as soon as they occur in order to minimise their effects on the patient.

Two cellulases from Scytalidium thermophilum were purified and characterized, exhibiting tolerance to glucose and cellobiose. Characterization of purified cellulases I and II by mass spectrometry revealed primary structure similarities with an exoglucanase and an endoglucanase, respectively. Molecular masses were 51.2 and 45.6 kDa for cellulases I and II, respectively, as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis. Cellulases I and II exhibited isoelectric points of 6.2 and 6.9 and saccharide contents of 11 and 93 %, respectively. Optima of temperature and pH were 60-65 °C and 4.0 for purified cellulase I and 65 °C and 6.5 for purified cellulase II. Both cellulases maintained total CMCase activity after 60 min at 60 °C. Cysteine, Mn(2+), dithiotreitol and ß-mercaptoethanol-stimulated cellulases I and II. The tolerance to cellulose hydrolysis products and the high thermal stabilities of Scytalidium cellulases suggest good potential for industrial applications.

Background: Hospital-acquired infections (HAI) are an important public health problem worldwide. Little information is available from African countries, but published data show that the burden of HAI is greater in Africa than in developed countries. In 2002, the World Health Organization (WHO) published guidelines for preventing HAI., Aim: To evaluate the impact of a hospital infection control programme on the prevalence of HAI among patients in a large Ugandan hospital., Methods: A one-day cross-sectional prevalence survey and a ward procedure survey were performed in Lacor Hospital in March 2010 using standardized questionnaires. All patients admitted to hospital not less than two days before the survey were eligible to participate in the prevalence survey. Modified WHO criteria for HAI were used. The ward procedure survey examined the procedures to prevent HAI. Several hospital infection control measures were subsequently implemented, in accordance with WHO infection control guidelines, starting in October 2010. The prevalence survey and ward procedure survey were repeated in October 2011., Findings: The prevalence of HAI was 34% in 2010 and 17% in 2011. The prevalence of infected patients reduced from 28% to 14%. The prevalence of HAI was lower in all age groups and for all types of HAI except urinary tract infections following the implementation of infection control activities., Conclusion: This study showed that HAI is an important problem in this large African hospital, and that the prevalence of HAI can be reduced effectively following the adoption of basic infection control procedures., (Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Although substrate conversion mediated by human monoaminooxidase (hMAO) has been associated with the deprotonated state of their amine moiety, data regarding the influence of protonation on substrate binding at the active site are scarce. Thus, in order to assess protonation influence, steered molecular dynamics (SMD) runs were carried out. These simulations revealed that the protonated form of the substrate serotonin (5-HT) exhibited stronger interactions at the protein surface compared to the neutral form. The latter displayed stronger interactions in the active site cavity. These observations support the possible role of the deprotonated form in substrate conversion. Multigrid docking studies carried out to rationalize the role of 5-HT protonation in other sites besides the active site indicated two energetically favored docking sites for the protonated form of 5-HT on the enzyme surface. These sites seem to be interconnected with the substrate/inhibitor cavity, as revealed by the tunnels observed by means of CAVER program. pK(a) calculations in the surface loci pointed to Glu³²⁷, Asp³²⁸, His⁴⁸⁸, and Asp¹³² as candidates for a possible in situ deprotonation step. Docking analysis of a group of inhibitors (structurally related to substrates) showed further interactions with the same two docking access sites. Interestingly, the protonated/deprotonated amine moiety of almost all compounds attained different docking poses in the active site, none of them oriented to the flavin moiety, thus producing a more variable and less productive orientations to act as substrates. Our results highlight the role of deprotonation in facilitating substrate conversion and also might reflect the necessity of inhibitor molecules to adopt specific orientations to achieve enzyme inhibition.

Background: Iron is essential for the maintenance of basic cellular processes. In the regulation of its cellular levels, ferritin acts as the main intracellular iron storage protein. In this work we present a mathematical model for the dynamics of iron storage in ferritin during the process of intestinal iron absorption. A set of differential equations were established considering kinetic expressions for the main reactions and mass balances for ferritin, iron and a discrete population of ferritin species defined by their respective iron content., Results: Simulation results showing the evolution of ferritin iron content following a pulse of iron were compared with experimental data for ferritin iron distribution obtained with purified ferritin incubated in vitro with different iron levels. Distinctive features observed experimentally were successfully captured by the model, namely the distribution pattern of iron into ferritin protein nanocages with different iron content and the role of ferritin as a controller of the cytosolic labile iron pool (cLIP). Ferritin stabilizes the cLIP for a wide range of total intracellular iron concentrations, but the model predicts an exponential increment of the cLIP at an iron content > 2,500 Fe/ferritin protein cage, when the storage capacity of ferritin is exceeded., Conclusions: The results presented support the role of ferritin as an iron buffer in a cellular system. Moreover, the model predicts desirable characteristics for a buffer protein such as effective removal of excess iron, which keeps intracellular cLIP levels approximately constant even when large perturbations are introduced, and a freely available source of iron under iron starvation. In addition, the simulated dynamics of the iron removal process are extremely fast, with ferritin acting as a first defense against dangerous iron fluctuations and providing the time required by the cell to activate slower transcriptional regulation mechanisms and adapt to iron stress conditions. In summary, the model captures the complexity of the iron-ferritin equilibrium, and can be used for further theoretical exploration of the role of ferritin in the regulation of intracellular labile iron levels and, in particular, as a relevant regulator of transepithelial iron transport during the process of intestinal iron absorption.

Aim of the Study: Cochlospermum vitifolium is a medicinal plant used for the treatment of diabetes, hepatobilary and cardiovascular illnesses. The aim of current study was to determine the in vivo antihypertensive and in vitro functional vasorelaxant mechanism of methanol extract of Cochlospermum vitifolium (MECv) and naringenin (NG)., Materials and Methods: Test material was assayed on rat isolated aorta rings test with- and without-endothelium to determine their vasorelaxant mechanism. Also, the in vivo antihypertensive effect was evaluated on spontaneously hypertensive rat (SHR) model. In addition, presence of NG into the extract was confirmed by reverse phase high performance liquid chromatography (RP-HPLC) analysis., Results: MECv (120 mg/kg) and NG (50 and 160 mg/kg) showed acute antihypertensive effects on SHR when systolic and diastolic pressure were decreased at 1 h and 24 h after administration, respectively. Vasorelaxant effect of MECv and NG was shifted to the right when endothelium-intact aortic rings were pre-incubated with L-NAME (10 microM) and ODQ (1 microM). Also, NG relaxant curves were displaced to the right in the presence of tetraethylammonium (TEA, 1 mM) and 2-aminopyridine (2-AP, 100 microM) on endothelium-denuded aortic rings., Conclusion: Experiments described above showed that MECv play an important role in hypertension regulation through NO synthesis and may be PGI(2) production and potassium channel activation on excessive endothelial dysfunction conditions. Unfortunately, presence of NG into the extract is not significant on bioactivity of the extract; however, this compound could be tested and evaluated as structural scaffold for future drug design for development of antihypertensive agents., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Mentha pulegium is common known as "poleo" and used for the treatment of diarrhea, headache and cough in Mexican traditional medicine. Organic extracts from aerial parts were evaluated to determine their spasmolytic action on rat isolated ileum test. Hexanic (HEMp), dichloromethanic (DEMp) and methanolic (MEMp) extracts induced a concentration-dependent (0.97 to 1000 microg/mL) antispasmodic effect on spontaneous contractions. DEMp was the most active extract; therefore, spasmolytic mechanism was investigated. This extract (200 microg/mL) induced a significant depression on cumulative concentration-response curve for carbachol and serotonin (P<0.05). Besides, extract decreased and shifted to the right KCl- and CaCl2-induced contraction curves. Moreover, pre-incubation with chlorpromazine (0.001 mM) shifted to the left the relaxant curve. Pre-treatment with L-NAME (1 mM), papaverine (0.01 mM), teophylline (0.01 mM), TEA (1 mM) and glybenclamide (0.1 mM) did not produced any changed of the relaxant curves of DEMp. Findings indicate that dichloromethanic extract of M. pulegium induced its spasmolytic effect through Ca2+-influx blockade, which may explain its traditional use against diarrhea.

Introduction: The word "constipation" is used by people to refer multiple symptoms such as infrequent stools, hard stools, excessive straining and feeling of incomplete evacuation. This variability is a confounding factor and may induce discrepancies between doctors and patients., Aim: to evaluate among the general population of 6 different cities of Mexico, what is meant by constipation., Material and Methods: A cross-sectional study was performed in the cities of Veracruz, Tampico, Tuxtepec, Colima, Puebla and San Luis Potosi (representing 4 geographical areas of Mexico). All subjects answer a questionnaire that assesses self-perception of constipation with the question: Do you consider yourself constipated? Frequency and stool form (Bristol), symptoms and associated factors to constipation were also evaluated. Rome III criteria for functional constipation (FC) and irritable bowel syndrome with constipation (IBS-C) were applied., Results: One thousand and forty one subjects were evaluated (mean age 35 +/- 15 years), 657 (63%) women. In our study, 87% (n = 907) had a bowel movement at least every 48 hours and most of them (67%) have stools type 3-4. Thirty four percent (n = 356) of subjects considered to have constipation, of whom 73 (21%) met criteria for FC, 65 (18%) for IBS-C and 218 subjects (61%) did not meet diagnostic criteria. The symptom that best defines constipation was straining (47%). Correlation and concordance between self-perception and the Rome criteria was 0.14 (p = 0.61)., Conclusions: In our population, 61% of subjects who perceived symptoms of constipation are not really constipated according to the criteria of Rome.

Endodontic and periodontal diseases can provide many diagnostic and management challenges to clinicians, particularly when they occur concurrently. As with all diseases, a thorough history combined with comprehensive clinical and radiographic examinations are all required so an accurate diagnosis can be made. This is essential since the diagnosis will determine the type and sequence of treatment required. This paper reviews the relevant literature and proposes a new classification for concurrent endodontic and periodontal diseases. This classification is a simple one that will help clinicians to formulate management plans for when these diseases occur concurrently. The key aspects are to determine whether both types of diseases are present, rather than just having manifestations of one disease in the alternate tissue. Once it is established that both diseases are present and that they are as a result of infections of each tissue, then the clinician must determine whether the two diseases communicate via the periodontal pocket so that appropriate management can be provided using the guidelines outlined. In general, if the root canal system is infected, endodontic treatment should be commenced prior to any periodontal therapy in order to remove the intracanal infection before any cementum is removed. This avoids several complications and provides a more favourable environment for periodontal repair. The endodontic treatment can be completed before periodontal treatment is provided when there is no communication between the disease processes. However, when there is communication between the two disease processes, then the root canals should be medicated until the periodontal treatment has been completed and the overall prognosis of the tooth has been reassessed as being favourable. The use of non-toxic intracanal therapeutic medicaments is essential to destroy bacteria and to help encourage tissue repair.

Background: To allow the survival of the population in the absence of nitrogen, some cyanobacteria strains have developed the capability of differentiating into nitrogen fixing cells, forming a characteristic pattern. In this paper, the process by which cyanobacteria differentiates from vegetative cells into heterocysts in the absence of nitrogen and the elements of the gene network involved that allow the formation of such a pattern are investigated., Methods: A simple gene network model, which represents the complexity of the differentiation process, and the role of all variables involved in this cellular process is proposed. Specific characteristics and details of the system's behavior such as transcript profiles for ntcA, hetR and patS between consecutive heterocysts were studied., Results: The proposed model is able to capture one of the most distinctive features of this system: a characteristic distance of 10 cells between two heterocysts, with a small standard deviation according to experimental variability. The system's response to knock-out and over-expression of patS and hetR was simulated in order to validate the proposed model against experimental observations. In all cases, simulations show good agreement with reported experimental results., Conclusion: A simple evolution mathematical model based on the gene network involved in heterocyst differentiation was proposed. The behavior of the biological system naturally emerges from the network and the model is able to capture the spacing pattern observed in heterocyst differentiation, as well as the effect of external perturbations such as nitrogen deprivation, gene knock-out and over-expression without specific parameter fitting.

Hydrophobic interaction chromatography (HIC) is a key technique for protein separation and purification. Different methodologies to estimate the hydrophobicity of a protein are reviewed, which have been related to the chromatographic behavior of proteins in HIC. These methodologies consider either knowledge of the three-dimensional structure or the amino acid composition of proteins. Despite some restrictions; they have proven to be useful in predicting protein retention time in HIC.