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In this paper, the autonomous trajectory-tracking problem for an Unmanned Aerial Vehicle (UAV) based on Sliding Mode Control (SMC) algorithms is treated. The control system is implemented in real-time to stabilize a commercial AR.Drone 2.0 quadrotor using monocular vision. The under-actuated mathematical model is based on the Newton-Euler formulation. The algorithm allows the stabilization of the quadrotor in all its states under the simultaneous effect of parametric uncertainties and constant external disturbances. The vision algorithm uses a monocular camera to estimate the vehicle's position. The experimental test results and numerical simulations show the effectiveness and robustness of the proposed controller. [ABSTRACT FROM AUTHOR]

This paper provides a novel chain observer for a class of Lipschitz nonlinear systems where the nonlinear measured outputs are corrupted by multiple time‐varying long delays. The main contribution is to synthesize a chain observer for a wider class of Lipschitz nonlinear systems with multiple outputs (described by Lipschitz nonlinear functions) with long time‐varying delays. In the design of the proposed observation scheme, the provided observer is comprised of a chain of state observers, where each one has a similar structure. Each observer is tasked to estimate the state over a short time horizon, whereas the first item of the chain provides the actual state estimation. Moreover, each item of the chain observer furnishes a proportional‐integral dynamical term which allows to compensate for the time‐delay effect. The observer gains are obtained from the solution of a set of delay‐dependent Linear Matrix Inequalities (LMIs), which is based on less restrictive LMI synthesis conditions. The convergence analysis relies on a Lyapunov–Krasovskii functional, which demonstrates that the observation error decays to zero. Numerical examples are given, in order to highlight the effectiveness of the provided observer. [ABSTRACT FROM AUTHOR]

This paper presents a new approach of the continuous‐discrete observer design for a class of uncertain state‐affine non‐linear systems. A high‐gain observer redesign is developed and analysed under insightful conditions. The proposed observer estimates the state vector by using system output measurements with long sampling times. This result is achieved by considering a persistent excitation condition that can be validated online. The performance of the proposed algorithm is evaluated under time‐varying sampled measurements to estimate the friction factor of a pipeline where the case of noisy sampled output measurements is also considered. [ABSTRACT FROM AUTHOR]

Microorganism culture is highly complex due to the different metabolic pathways, which are very complex. A metabolic phenomenon called overflow is a challenge to overcome in automatic control tasks of microorganism cultures. In this study, a nonlinear algorithm by sliding modes (sliding mode nonlinear control, SMNC) is proposed for the robust regulation of a fed-batch bioreactor in the presence of parametric and system perturbations. A control design is obtained using Lyapunov functions by techniques to propose a control law such that it is robust, only the output signals (biomass and volume) are used, and the reaction rates do not have to be wholly known. Therefore, a novel and simple controller capable of solving the above problems is obtained.

Introduction. Students with autism spectrum disorder (ASD) experience clinical or subclinical levels of anxiety which problematizes the possibilities of communication and social interaction. Current educational demands require the exploration of variables linked to the mediation of teachers' responses to the anxiety of students with ASD. Objective. To propose a predictive model based on mediating variables of teachers' responses to the anxiety of students with ASD in inclusive schools. Methods. This manuscript is focused on the review of the variables: knowledge about ASD, emotional regulation strategies, experience in special/inclusive education, and teachers' attitudes towards inclusion. Results. The evidence suggests that the variables reviewed are key in the responses of teachers to the anxiety of students with ASD. Based on this finding, a model is proposed that associates high knowledge about ASD, cognitive reassessment as a strategy for emotional regulation, positive attitude, and experience in special and/ or inclusive education with responses from teachers that promote autonomy, while indicators such as low knowledge about students with ASD, expressive suppression as an emotional regulation strategy, negative attitude, and little experience in special and/ or inclusive education are related to responses that problematize anxiety symptoms in students with ASD. Conclusion. The predictive model proposed here is speculative, but theoretically, it paves the way for possible empirical studies that demonstrate its validity.

This article addresses the problem of controlling the growth of microalgae originating in Mexican rivers, especially in the state of Sinaloa, Culiacan River. For this purpose, a robust, high-gain nonlinear observer is proposed to estimate the unknown disturbance in the cultivation of mixotrophic microalgae with the presence of organic nutrients. Once a perturbation function related to the change of ambient light is estimated, an output feedback control for the photobioreactor is proposed, in which through Lyapunov’s convergence functions, the final boundary stability conditions are obtained. Thus, a turbidity sensor was designed for Spirulina platensis, a native microalgae of Culiacan River, which is presented using the MATLAB-Arduino programming environment. This sensor is calibrated using biomass culture and is a low-cost device. Through the numerical study, the feasibility and performance of the control and the observer are evaluated. Finally, real-time experimental evaluations are made based on the literature, studying the use of robust controllers in a photobioreactor with a mixed culture, in the presence of environmental changes in lighting.

Radiotherapy is a key treatment option for a wide variety of human tumors, employed either alone or alongside with other therapeutic interventions. Radiotherapy uses high-energy particles to destroy tumor cells, blocking their ability to divide and proliferate. The effectiveness of radiotherapy is due to genetic and epigenetic factors that determine how tumor cells respond to ionizing radiation. These factors contribute to the establishment of resistance to radiotherapy, which increases the risk of poor clinical prognosis of patients. Although the mechanisms by which tumor cells induce radioresistance are unclear, evidence points out several contributing factors including the overexpression of DNA repair systems, increased levels of reactive oxygen species, alterations in the tumor microenvironment, and enrichment of cancer stem cell populations. In this context, dysregulation of microRNAs or miRNAs, critical regulators of gene expression, may influence how tumors respond to radiation. There is increasing evidence that miRNAs may act as sensitizers or enhancers of radioresistance, regulating key processes such as the DNA damage response and the cell death signaling pathway. Furthermore, expression and activity of miRNAs have shown informative value in overcoming radiotherapy and long-term radiotoxicity, revealing their potential as biomarkers. In this review, we will discuss the molecular mechanisms associated with the response to radiotherapy and highlight the central role of miRNAs in regulating the molecular mechanisms responsible for cellular radioresistance. We will also review radio-miRs, radiotherapy-related miRNAs, either as sensitizers or enhancers of radioresistance that hold promise as biomarkers or pharmacological targets to sensitize radioresistant cells., Competing Interests: Conflicts of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

This article introduces an observer-based control strategy tailored for regulating plasma glucose in type 1 diabetes mellitus patients, addressing challenges like unknown time-varying delays and meal disturbances. This control strategy is based on an extended Bergman minimal model, a nonlinear glucose-insulin model to encompass unknown inputs, such as unplanned meals, exercise disturbances, or delays. The primary contribution lies in the design of an observer-based state feedback control in the presence of unknown long delays, which seeks to support and enhance the performance of the traditional artificial pancreas by considering realistic scenarios. The observer and control gains for the observer-based control are computed through linear matrix inequalities formulated from Lyapunov conditions that guarantee closed-loop stability. This design deploys a soft and gentle dynamic response, similar to a natural pancreas, despite meal disturbances and input delays. Numerical tests demonstrate the scheme's effectiveness in glycemic level regulation and hypoglycemic episode avoidance., (© 2024 John Wiley & Sons Ltd.)

The cytosolic enzymes N-Acetyl Transferases 1 and 2 (NATs) transfer an acetyl group from acetyl-CoA to a xenobiotic substrate. NATs are regulated at the genetic and epigenetic levels by deacetylase enzymes such as sirtuins. The enzymatic expression of NAT1, NAT2, and SIRT1 was evaluated by flow cytometry, as well as the enzymatic activity of NATs by cell culture and HPLC analysis. Six SNPs were determined through genotyping. T2D patients (n = 29) and healthy subjects (n = 25) with a median age of 57 and 50, respectively, were recruited. An increased enzyme expression and a diminished NAT2 enzymatic activity were found in cells of T2D patients compared to the control group, while NAT1 was negatively correlated with body fat percentage and BMI. In contrast, Sirtuin inhibition increased NAT2 activity, while Sirtuin agonism decreased its activity in both groups. The analysis of NAT2 SNPs showed a higher frequency of rapid acetylation haplotypes in T2D patients compared to the control group, possibly associated as a risk factor for diabetes. The enzymatic expression of CD3+NAT2+ cells was higher in the rapid acetylators group compared to the slow acetylators group. The levels and activity of NAT1 were associated with total cholesterol and triglycerides. Meanwhile, CD3+NAT2+ cells and NAT2 activity levels were associated with HbA1c and glucose levels. The results indicate that NAT2 could be involved in metabolic processes related to the development of T2D, due to its association with glucose levels, HbA1c, and the altered SIRT-NAT axis. NAT1 may be involved with dyslipidaemias in people who are overweight or obese., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier B.V.)

Background: Rheumatoid Arthritis (RA) is a chronic autoimmune disease that has a prevalence of over one percent of the world population, causing substantial pain, joint deformity, and functional disability in patients. The identification and measurement of miRNAs are relatively easy to perform. Future studies will corroborate if miRNAs can fulfill their roles as biomarkers with either predictive or diagnostic evaluation of treatment potential and provide actual clinical utility., Methods: In the last decade, various advances have been made regarding the identification of the origin and exact functions of miRNAs, allowing us to have a potential use both in the research and clinical fields., Objective: This systematic review aimed to collect, analyze, and improve the current understanding of RA-related miRNAs and their applicability in therapeutics. A bibliographic search of the miRNAs involved in RA was carried out, and through the use of databases, their target genes and small molecules that had some relationship with their expression were searched. The analysis of these data was done through structural network analysis., Results: During the network analysis, miR-30a, miR-30c, let-7a, miR-144, miR-17-5p, miR-124, miR -23b, miR-23, miR-15a, miR-16 were the most connected, which could be used as possible biomarkers or be candidates for further analysis due to their interaction with other miRNAs and genes., Conclusion: Additionally, this is the first systematic review, in which we proposed that small compounds like toxicants and drugs could have a potential role within RA because they regulate the expression of miRNAs involved in this pathology. Some of these compounds are commonly found as environmental contaminants, and others as drugs. These ideas open a new panorama of understanding RA, proposing possible causes or treatments against this pathology. Therefore, these small molecules would give us some indication of a relationship with RA, thereby helping in seeking causes, treatment, or prevention of this disease., Conclusion: This is the first time it is intended to use structural network analysis to determine possible biomarkers of AR for diagnosis and prognosis through the expression of these miRNAs and their relationship with compounds of daily life., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Bone repair aims to restore the anatomical, biomechanical, and functional integrity of the affected structure. Here we study the effects of ascorbic acid (AA) and epidermal growth factor (EGF) applied in a single dose and in combination on the repair of a noncritical bone defect model., Methods: Twenty-four rats were divided into four groups: an intact G-1 control group, and three groups that underwent a noncritical bone defect in the right tibia: G-2 treated with AA, G-3 treated with EGF, and G-4 treated with AA in combination with EGF. After 21 days of treatment, rats were sacrificed, the tibias were dissected and a destructive biomechanical analysis of three-point flexion test was performed in a universal testing machine; the values of stiffness, resistance, maximum energy, and energy at maximum load were statistically compared., Results: G-3 and G-4 recovered the biomechanical properties of strength and stiffness of an intact tibia 3 weeks after their application. Not so the energy and energy at maximum load. For G-2, only the stiffness of an intact tibia was recovered., Conclusions: EGF and AA-EGF applied to a noncritical bone defect in the rat tibia favors the recovery of bone resistance and stiffness.

The number of research related to traumatic experiences in people with autism spectrum disorder (ASD) has grown exponentially, yet there are no bibliometric studies in this field. This article aimed to analyze the literature related to trauma and ASD published in Web of Science (WoS). Papers on trauma and ASD were retrieved from the WoS. Analysis and visualization of selected documents were performed using MS Excel (v16.0), VOS viewer (version 1.6.15), and R package (Biblioshiny, version 2.0). A total of 147 articles were included in this study. The results showed that production has been increasing over the last few years. Among the countries identified, the USA published the largest number of articles. Arvid Nikolai Kildahl, Sissel Berge Helverschou, and Liliana Dell'Osso were the authors with the most number of publications on this topic, and Autism was the most productive journal. The main research topics associated with ASD were post-traumatic stress and traumatic experiences in childhood. This bibliometric study contributes to understanding research trends on trauma and ASD by evaluating relevant publications in the last decades. The results of this bibliometric analysis can serve as a basis and orientation for new studies.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in socialization. The amount of scientific research results on motherhood related to ASD has grown exponentially; however, there are no bibliometric studies in this field. Objective: This article aimed to analyze scientific research on motherhood related to the autism spectrum published in WoS. Articles on motherhood related to ASD were retrieved from the Web of Science (WoS). The advanced search interface used was "Title of the article, Abstract, Keywords". The analysis and visualization of the selected documents and their data were performed using a wide range of tools and software such as MS Excel (v16.0), VOS viewer (version 1.6.15), and R packages (Biblioshiny, version 2.0). A total of 1660 articles were included in this study. Most of the publications were original articles. The United States published the most significant number of articles among the countries identified. P.R. Hastings, M.M. Seltzer, and J. Van de Water were the main authors. The Journal of Autism and Developmental Disorders was the most productive and impactful journal. The main research topics were related to mental health and social support in the role of motherhood. This desk study provides researchers with a comprehensive understanding of ASD-related maternity research trends by evaluating relevant publications in recent decades. The results of this bibliometric analysis can serve as a basis and orientation for new studies.

Since their discovery, arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2, respectively) have been associated with the metabolism of xenobiotics. NAT2 is the main factor in the therapeutic success of tuberculosis treatment due to its role in the biotransformation of isoniazid. However, researchers have started to investigate the possible participation of NAT1 and NAT2 (NATs) in carcinogenesis, although the mechanisms have not been elucidated fully. NATs enzymatic activity is essential in some types of cancer, such as breast cancer and acute lymphoblastic leukemia. Whether NAT1 and/or NAT2 participate in insulin resistance level in diabetes mellitus or in the immune system remains to be explored. Therefore, it is clear that its role in cell physiology has more implications than just metabolizing compounds., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic, affecting more than 219 countries and causing the death of more than 5 million people worldwide. The genetic background represents a factor that predisposes the way the host responds to SARS-CoV-2 infection. In this sense, genetic variants of ACE and ACE2 could explain the observed interindividual variability to COVID-19 outcomes. In order to improve the understanding of how genetic variants of ACE and ACE2 are involved in the severity of COVID-19, we included a total of 481 individuals who showed clinical manifestations of COVID-19 and were diagnosed by reverse transcription PCR (RT-PCR). Genomic DNA was extracted from peripheral blood and saliva samples. ACE insertion/deletion polymorphism was evaluated by the high-resolution melting method; ACE single-nucleotide polymorphism (SNP) (rs4344) and ACE2 SNPs (rs2285666 and rs2074192) were genotyped using TaqMan probes. We assessed the association of ACE and ACE2 polymorphisms with disease severity using logistic regression analysis adjusted by age, sex, hypertension, type 2 diabetes, and obesity. The severity of the illness in our study population was divided as 31% mild, 26% severe, and 43% critical illness; additionally, 18% of individuals died, of whom 54% were male. Our results showed in the codominant model a contribution of ACE2 gene rs2285666 T/T genotype to critical outcome [odds ratio (OR) = 1.83; 95%CI = 1.01-3.29; p = 0.04] and to require oxygen supplementation (OR = 1.76; 95%CI = 1.01-3.04; p = 0.04), in addition to a strong association of the T allele of this variant to develop critical illness in male individuals (OR = 1.81; 95%CI = 1.10-2.98; p = 0.02). We suggest that the T allele of rs2285666 represents a risk factor for severe and critical outcomes of COVID-19, especially for men, regardless of age, hypertension, obesity, and type 2 diabetes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Martínez-Gómez, Herrera-López, Martinez-Armenta, Ortega-Peña, Camacho-Rea, Suarez-Ahedo, Vázquez-Cárdenas, Vargas-Alarcón, Rojas-Velasco, Fragoso, Vidal-Vázquez, Ramírez-Hinojosa, Rodríguez-Sánchez, Barrón-Díaz, Moreno, Martínez-Ruiz, Zayago-Angeles, Mata-Miranda, Vázquez-Zapién, Martínez-Cuazitl, Barajas-Galicia, Bustamante-Silva, Zazueta-Arroyo, Rodríguez-Pérez, Hernández-González, Coronado-Zarco, Lucas-Tenorio, Franco-Cendejas, López-Jácome, Vázquez-Juárez, Magaña, Cruz-Ramos, Granados, Hernández-Doño, Delgado-Saldivar, Ramos-Tavera, Coronado-Zarco, Guajardo-Salinas, Muñoz-Valle, Pineda, Martínez-Nava and López-Reyes.)

Summary Statement: A 2A receptor required previous D 2 receptor activation to modulate Ca 2+ currents. Istradefylline decreases pramipexole modulation on Ca 2+ currents. Istradefylline reduces A 2A  + neurons activity in striatial microcircuit, but pramipexole failed to further reduce neuronal activity.

Introduction: The NLR family pyrin domain containing 3 (NLRP3) signaling pathway has an important role in inflammation mediated by monosodium urate crystals in gout, and the characterization of single nucleotide polymorphisms (SNPs) have helped to recognize disease susceptibility., Objective: The aim of this review is to provide an overview of the potential role of the inflammasome gene SNPs as a susceptibility factor for gout, discussing the current evidence available., Methods: This review analyzes the relevant literature in the field of inflammasome SNPs and gout published in the last 10 years. The systematic research was performed in 16 articles, including both the SNPs associated and those not associated with gout, with the goal to have a complete overview., Results: Sixty-nine SNPs from 10 different genes have been reported in the literature. Of these, 13 SNPs present association with gout susceptibility in different populations, while 56 have been established as not being associated with the disease., Conclusions: This review is a summary of the potential role of inflammasome gene SNPs and their association with gout risk, all of them related with NLRP3 inflammasome signaling, suggesting these polymorphisms are susceptibility candidates and genetic markers for gout. From the 69 SNPs analyzed in the literature, 13 of them have been associated with gout as follows: NLRP3 (rs3806268 and rs10754558), CARD8 (rs2043211), TLR4 (rs2149356), CD14 (rs2569190), IL-1β (rs1143623), P2RX7 (rs2230911, rs1653624, rs7958316 and rs17525809) and PPARGC1B (rs45520937, rs10491360 and rs7712296) in different populations., (© 2021 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

The rostromedial tegmental nucleus (RMTg) is a bilateral structure localized in the brainstem and comprise of mainly GABAergic neurons. One of the main functions of the RMTg is to regulate the activity of dopamine neurons of the mesoaccumbens pathway. Therefore, the RMTg has been proposed as a modulator of the reward system and adaptive behaviors associated to reward learning. The RMTg receives an important glutamatergic input from the lateral habenula. Also, it receives cholinergic inputs from the laterodorsal and pedunculopontine tegmental nuclei. Previously, it was reported that nicotine increases glutamate release, evoked by electric stimulation, in the RMTg nucleus. However, the mechanisms by which nicotine induces this effect were not explored. In the present work, we performed electrophysiological experiments in brainstem slices to study the effect of nicotine on spontaneous excitatory postsynaptic currents recorded from immunocytochemically identified RMTg neurons. Also, we used calcium imaging techniques to explore the effects of nicotine on multiple RMTg neurons simultaneously. We found that nicotine promotes the persistent release of glutamate through the activation of α7 nicotinic acetylcholine receptors present on glutamatergic afferents and by a mechanism involving calcium release from intracellular stores. Through these mechanisms, nicotine increases the excitability and synchronizes the activity of RMTg neurons. Our results suggest that the RMTg nucleus mediates the noxious effects of the nicotine, and it could be a potential therapeutic target against tobacco addiction., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Castillo-Rolón, Ramírez-Sánchez, Arenas-López, Garduño, Hernández-González, Mihailescu and Hernández-López.)

The aim of this study was to establish and validate an alternative high-performance liquid chromatography method for simultaneous quantification of pyrazinamide, isoniazid, acetyl-isoniazid and rifampicin in plasma of patients under treatment for tuberculosis. The performed method was lineal (r 2  > 0.99) in the range of 2.00-50.00 μg/mL for pyrazinamide, 0.50-20.00 μg/mL for both acetyl-isoniazid and isoniazid, and 1.20-25.00 μg/mL for rifampicin. Precision and trueness were demonstrated with coefficient of variation < 15% and deviations < 15%, respectively, for quality controls samples. The lower limits of quantification were 2.00, 0.50, 0.50, and 1.20 μg/mL for pyrazinamide, isoniazid, acetyl-isoniazid and rifampicin, respectively. The method was applied for the analysis of plasma from patients with tuberculosis. This method allowed ensuring reliable quantification of the target compounds and their pharmacokinetics parameters. In general, the mean values of maximum concentration of each antituberculosis drug were located within their respective reference therapeutic ranges. However, patients with sub-therapeutic plasma concentrations of isoniazid and rifampicin were detected. This is the first analytical technique that simultaneously quantifies isoniazid, acetyl-isoniazid, rifampicin, and pyrazinamide concentrations from plasma samples by high-performance liquid chromatography with ultraviolet/visible. The proposed method could be applied for therapeutic drug monitoring and pharmacokinetics studies of the four compounds throughout the treatment of tuberculosis patients., (© 2020 Wiley-VCH GmbH.)

Previous studies showed that mecamylamine a noncompetitive and nonspecific blocker of nicotinic acetylcholine receptors (nAChRs), stimulates the activity of the dorsal raphe nucleus (DRN) serotonergic neurons and DRN serotonin (5-HT) release. In the present study, the mechanisms involved in these mecamylamine-induced effects were examined using electrophysiology and calcium-imaging studies, both performed in Wistar rat midbrain slices. Mecamylamine (0.5-9 μM), bath administered, increased the firing frequency of identified 5-HT DRN neurons by a maximum of 5% at 3 μM. This effect was accompanied by a 112 % increase in the frequency of spontaneous excitatory postsynaptic currents of 5-HT DRN neurons. It was blocked by the AMPA/kainate receptor blocker CNQX (10 μM) and by the specific α4β2 nAChRs blocker dihydro-β-erythroidine (100 nM) but was not affected by tetrodotoxin (TTX, 500 nM). Simultaneously, mecamylamine produced a 58 % decrease in the frequency of GABAergic spontaneous inhibitory postsynaptic currents, an effect that was not influenced by TTX. Calcium-imaging studies support the results obtained with the electrophysiological studies by showing that mecamylamine (3 μM) increases the activity of a cell population located in the midline of the DRN, which was sensitive to the inhibitory effects of 8-OH-DPAT, an agonist at 5-HT 1A receptors. It is assumed that mecamylamine, in low concentrations, acts as an agonist of α4β2 nAChRs present on the glutamatergic DRN terminals, thus increasing intra-raphe glutamate release. This stimulatory effect is reinforced by the decrease in DRN GABA release, which is dependent on the mecamylamine-induced blockade of α7 nAChRs located on DRN GABAergic terminals. We hypothesize that at least a part of mecamylamine antidepressant effects described in animal models of depression are mediated by an increase in DRN 5-HT release., (Copyright © 2020. Published by Elsevier Inc.)

Calicivirus infection causes intrinsic apoptosis, leading to viral propagation in the host. During murine norovirus infection, a reduction in the anti-apoptotic protein survivin has been documented. Here we report that in feline calicivirus infection, a downregulation of the anti-apoptotic proteins survivin and XIAP occur, which correlates with the translocation of the pro-apoptotic protein Smac/DIABLO from the mitochondria to the cytoplasm and the activation of caspase-3. Inhibition of survivin degradation by lactacystin treatment caused a delay in apoptosis progression, reducing virus release, without affecting virus production. However, the overexpression of survivin caused a negative effect in viral progeny production. Overexpression of the leader of the capsid protein (LC), but not of the protease-polymerase NS6/7, results in the downregulation of survivin and XIAP, caspase activation and mitochondrial damage. These results indicate that LC is responsible for the induction of apoptosis in transfected cells and most probably in FCV infection., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Acute lymphoblastic leukemia (ALL) is one of the main causes of death in children and is associated with both genetic susceptibility and environmental factors. Genes encoding the arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) isoenzymes are highly polymorphic among populations. Single-nucleotide polymorphism analysis was performed by real-time polymerase chain reaction from the genomic DNA of 225 healthy subjects and 57 children with ALL diagnoses. Significant associations were found between the development of ALL and the presence of the haplotypes NAT1*3 (Odds ratio [OR], 2.1), NAT1*4 (OR, 1.92), NAT2*6B (OR, 3.30), NAT2*6J (OR, 3.25) and NAT2*7A (OR, 2.45) and the NAT1 rapid (OR, 6.69) and NAT2 slow phenotypes (OR, 2.95). Our results indicate that haplotypes that provide rapid NAT1 and slow NAT2 acetylating phenotypes may influence the development of ALL in children.

Background: We have reported the presence of varicella-zoster virus (VZV) DNA and viral particles in the cerebrospinal fluid (CSF) of multiple sclerosis (MS) patients during exacerbation. It is not known whether these viruses are infective., Aim: To determine whether the VZV found in CSF of MS patients in exacerbation phase are infective., Methods: VZV found in CSF of MS patients was quantified by qPCR. Vero E6 cell cultures were incubated with CSF of five MS cases positive for VZV DNA, containing herpes-like viral particles. Propagated virus harvested from these cultures were used to infect new VeroE6 cells. Localization of an immediate-early and a late structural VZV proteins was monitored by confocal microscopy after 72 h. CSF from five non-inflammatory neurological (NIN) patients were used as controls., Results: A cytopathic effect was found in cultured cells inoculated with CSF from MS patients. Both, structural VZV glycoprotein (gB) and immediate-early VZV protein (IE62) were detected in Vero E6 cultures inoculated with samples from all five MS cases. CSF from control patients produced no effect on Vero E6 cells., Conclusion: When present in the CSF at relapses of MS, VZV is infective under in vitro conditions., (Copyright © 2018 IMSS. Published by Elsevier Inc. All rights reserved.)

Introduction: Cardiovascular disease is the main cause of mortality worldwide. In women, its incidence increases at the sixth decade of life, coinciding with postmenopause. Whether this effect is due to menopause-related hormonal changes is not known., Objective: To evaluate the differences in cardiovascular risk in pre- and postmenopausal women by means of the Globorisk risk scale, the triglyceride/high-density lipoproteins cholesterol (Tg/HDL-C) ratio and metabolic syndrome (MS) criteria., Method: Cross-sectional study that included 408 women from 40 to 60 years of age; anthropometric measurements and biochemical determinations were performed. The participants were classified as premenopausal and postmenopausal. Cardiovascular risk was assessed using the MS criteria, the Globorisk risk calculator and the Tg/HDL-C ratio., Results: Postmenopausal women showed a significant increase in waist circumference, total cholesterol and triglycerides in comparison with premenopausal women. Significant associations were found between hormonal state and Globorisk measured cardiovascular risk (OR = 2.50; 95 % CI = 1.67-3.74) and the Tg/HDL-C ratio (OR = 1.66; 95 % CI = 1.09-2.52)., Conclusion: Cardiovascular risk factors have a higher prevalence in postmenopause. The Globorisk scale and Tg/HDL-C ratio identify cardiovascular risk in postmenopausal women., (Copyright: © 2018 SecretarÍa de Salud.)

Tuberculous meningitis (TBM) is the most severe form of tuberculosis. It is caused by Mycobacterium tuberculosis (M. tuberculosis; MT) and it is very difficult to diagnose. The symptoms are similar to other infectious neurological diseases, such as neurocysticercosis, neuroborreliosis, or herpes viral infection. The aim of this study was to identify tuberculosis (TB) in cases of meningitis with clinical and laboratory evidence suggestive of TBM, and to confirm our findings with molecular tests for TB infection. We recruited patients with neurological symptoms who were examined at the neurology services of Hospitals of Instituto Mexicano del Seguro Social (IMSS) in Mexico City. A total of 144 consecutive patients with suggestive infectious meningitis were initially included; 94 cases of meningitis with clinical and laboratory evidence suggestive of TBM were included, but only 50 of these cases fulfilled the criteria for probable TBM. As the controls, we included 50 cases of meningitis with clinical and laboratory evidence suggestive of non-TBM. Cerebrospinal fluid (CSF) was collected from all 100 patients (cases and controls) and tested for TB by multiplex and nested PCR analyses. Nested PCR detected 0.1 fg of M. tuberculosis DNA. TB infection was confirmed with molecular tests in 49 patients from the 50 cases suggestive of TBM and in 1 of the 50 non-TBM cases. The analysis exhibited a sensitivity of 98.0%, a specificity of 92.0%, a positive predictive value of 88.0% and a negative predictive value of 98.0%. The use CSF for the analyses proved to be effective for the rapid diagnosis of TBM using a developed system of multiplex and nested PCR analyses in patients presenting neurological symptoms.

The external globus pallidus (GPe) is central for basal ganglia processing. It expresses muscarinic cholinergic receptors and receives cholinergic afferents from the pedunculopontine nuclei (PPN) and other regions. The role of these receptors and afferents is unknown. Muscarinic M1-type receptors are expressed by synapses from striatal projection neurons (SPNs). Because axons from SPNs project to the GPe, one hypothesis is that striatopallidal GABAergic terminals may be modulated by M1 receptors. Alternatively, some M1 receptors may be postsynaptic in some pallidal neurons. Evidence of muscarinic modulation in any of these elements would suggest that cholinergic afferents from the PPN, or other sources, could modulate the function of the GPe. In this study, we show this evidence using striatopallidal slice preparations: after field stimulation in the striatum, the cholinergic muscarinic receptor agonist muscarine significantly reduced the amplitude of inhibitory postsynaptic currents (IPSCs) from synapses that exhibited short-term synaptic facilitation. This inhibition was associated with significant increases in paired-pulse facilitation, and quantal content was proportional to IPSC amplitude. These actions were blocked by atropine, pirenzepine, and mamba toxin-7, suggesting that receptors involved were M1. In addition, we found that some pallidal neurons have functional postsynaptic M1 receptors. Moreover, some evoked IPSCs exhibited short-term depression and a different kind of modulation: they were indirectly modulated by muscarine via the activation of presynaptic cannabinoid CB1 receptors. Thus pallidal synapses presenting distinct forms of short-term plasticity were modulated differently., (Copyright © 2015 the American Physiological Society.)