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Given the increased prevalence of overweight and obesity in adults in Colombia, estimating the effect of sociodemographic factors on overweight and obesity is crucial for creating and implementing public health policies. A pooled analysis was performed using a multinomial logistic regression model through Colombian Nutritional Situation Surveys held in 2010 and 2015. The study included Colombian adults between 18 and 64 years old (n = 162,119). Overall, the prevalence of obesity increased from 16.47 percent in 2010 to 18.67 percent in 2015, being higher in women than in men in both surveys. Multinomial logistic regression analysis revealed that the most critical factor of being overweight and obese were older age, having a higher level of education, being engaged in household activities, and living in regions other than the country's capital. Additionally, for obesity, belonging to the Afro Colombian racial-ethnic group and being a woman were associated with an increased probability. In conclusion, these results provide more information on the sociodemographic factors related to overweight and obesity, which will help focus public health policies on higher-risk populations, such as racial-ethnic communities., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The brain and spinal cord originate from a neural tube that is preceded by a flat structure known as the neural plate during early embryogenesis. In humans, failure of the neural plate to convert into a tube by the fourth week of pregnancy leads to neural tube defects (NTDs), birth defects with serious neurological consequences. The signaling mechanisms governing the process of neural tube morphogenesis are unclear. Here we show that in Xenopus laevis embryos, neural plate cells release glutamate during neural plate folding in a Ca 2+ and vesicular glutamate transporter-1 (VGluT1)-dependent manner. Vesicular release of glutamate elicits Ca 2+ transients in neural plate cells that correlate with activation of Erk1/2. Knocking down or out VGluT1 leads to NTDs through increased expression of Sox2, neural stem cell transcription factor, and neural plate cell proliferation. Exposure during early pregnancy to neuroactive drugs that disrupt these signaling mechanisms might increase the risk of NTDs in offspring.

Leishmaniasis is a significant public health concern, with dogs as the primary reservoir in urban scenarios and facilitating transmission. Diagnosing infected dogs is a crucial step for public health interventions, and the development of new diagnostic platforms can significantly enhance efforts in various regions worldwide. Given the limited availability of diagnostic methods in Colombia, this study evaluates the effectiveness of an Indirect Enzyme-Linked Immunosorbent Assay (ELISA) based on the recombinant protein rLicNTPDase-2 to detect Leishmania in infected dogs. Serum samples were collected from dogs in both endemic and non-endemic areas and classified as natural standards based on prior parasitological diagnoses. The results revealed 24 true positives (TP) and 9 true negatives (TN). Subsequently, the test was then validated with samples from symptomatic and asymptomatic animals, alongside the standards, yielding a specificity of 96 %, a sensitivity of 81 %, efficiency of 90.6 %, a positive predictive value of 92.8 %, and a negative predictive value of 89.6 %. The positive likelihood ratio (RV+) was 20, while the negative likelihood ratio (RV-) was 0.19, indicating high relevance and a robust clinical utility. The area under the curve (AUC) was 1.00, suggesting that the test has excellent discriminatory ability, significantly deviating from the reference diagonal. This is further supported by the significant difference(p < 0.0001) between TN and TP results determined by Fisher's exact test. Involving 163 animals showed 47 % positive and 46 % negative results with a significant difference (p < 0.05) in the mean optical density (OD) values between positive and negative samples. These findings indicate that the ELISA test effectively differentiates between positive and negative samples based on OD values. This study suggests that ELISA based on the recombinant antigen rLicNTPDase-2 could serve as a viable alternative for the serodiagnosis of leishmaniasis in canines in Colombia., Competing Interests: Declaration of competing interest There are no competing interests that may influence the results of this study., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Obesity rates in Colombia are increasing, with variations among racial and ethnic groups. Studies on adult obesity often address socio-economic status, gender, and education but neglect racial-ethnic influences, notably in areas like Quibdó. Therefore, based on the theory of triadic influence, we conducted a qualitative study to identify biobehavioural, social, and cultural phenomena that, from the perspectives of the participants, influence the onset of obesity in Afro-Colombian and indigenous in Quibdó in 2022. The stratification variables were race, ethnicity (Afro-Colombian and Indigenous), and educational level (secondary or higher). Based on a literature review of qualitative studies that commonly explored food culture, nutritional status, and physical activity in analysing obesity within racial and ethnic populations, we incorporated these categories into our research methodology through semi-structured interviews. A framework analysis was used as a qualitative methodology to organise and analyse the collected data. We conducted 21 semi-structured interviews, 13 with the Afro-Colombian population and eight with indigenous inhabitants. The results indicate that cultural beliefs, forced displacement/migration, and alterations in public order have resulted in changes in food security, food culture, and physical activity practices, affecting the onset of obesity. Notably, distinctions in cultural beliefs regarding food culture and health as factors influencing obesity were observed between Afro-Colombians and the Indigenous populations; however, educational differences within the same racial ethnic group were not predominant. Findings indicate obesity is influenced by cultural, social, and biobehavioural factors, especially in regions with racial-ethnic communities facing complex conditions, necessitating targeted racial-ethnic public health policies., Competing Interests: The authors declare no competing interests., (© The Author(s) 2024.)

Background: Congenital heart disease is the most common congenital condition worldwide, with a prevalence of 80 cases per 10 000 live births. In addition to perinatal morbidity and mortality, it entails long-term consequences such as multiple surgeries, prolonged hospitalizations, lifelong cardiac follow-up, reduced quality of life, risk of heart failure, and premature mortality in adulthood. This significant health and economic burden on healthcare systems and families highlights the relevance of evaluating the cost-effectiveness of methods for early detection of this condition. Objective: To conduct a systematic literature review (SLR) to identify and analyze existing economic evaluations on prenatal detection of congenital heart diseases through ultrasound, focusing on the reported cost-effectiveness results and the methodological quality of the evaluated studies according to established criteria. Methods: An SLR of economic evaluations was conducted following PRISMA guidelines. A quantitative synthesis of key methodological components of each economic evaluation was performed. The incremental medical costs, effectiveness measures, and cost-effectiveness ratios reported in each study were compiled and compared. The methodological quality was assessed according to compliance with the 24 CHEERS criteria. Results: We found 785 articles, of which only 7 met all inclusion criteria. Most were cost-effectiveness analyses, with the most common outcome being number of cases detected. Screening with only 4-chamber views interpreted by general practitioners or cardiologists were dominant strategies compared with screening with 4-chamber plus outflow views interpreted by a general practitioner. Fetal echocardiography was most effective but most expensive. Screening with 4-chamber and outflow view, followed by referral to a specialist, were recommended as the least expensive strategy per defect detected. On average, articles met 17 of the 24 CHEERS criteria. Discussion: While recent cost-effectiveness analyses demonstrated improved methodological quality, there was a lack of homogeneity due to differences in comparators and population subgroups analyzed. Despite this heterogeneity, fetal ultrasonography screening was consistently identified as a cost-effective strategy, with its cost-effectiveness heavily influenced by the expertise of the interpreting physician. Conclusion: Most studies recommend implementing obstetric ultrasonography screening, without routine fetal echocardiography, for detecting congenital heart diseases.

Indole alkaloids are the main bioactive molecules of the Gelsemium genus plants. Diverse reports have shown the beneficial actions of Gelsemium alkaloids on the pathological states of the central nervous system (CNS). Nevertheless, Gelsemium alkaloids are toxic for mammals. To date, the molecular targets underlying the biological actions of Gelsemium alkaloids at the CNS remain poorly defined. Functional studies have determined that gelsemine is a modulator of glycine receptors (GlyRs) and GABA A receptors (GABA A Rs), which are ligand-gated ion channels of the CNS. The molecular and physicochemical determinants involved in the interactions between Gelsemium alkaloids and these channels are still undefined. We used electrophysiological recordings and bioinformatic approaches to determine the pharmacological profile and the molecular interactions between koumine, gelsemine, gelsevirine, and humantenmine and these ion channels. GlyRs composed of α1 subunits were inhibited by koumine and gelsevirine (IC 50 of 31.5 ± 1.7 and 40.6 ± 8.2 μM, respectively), while humantenmine did not display any detectable activity. The examination of GlyRs composed of α2 and α3 subunits showed similar results. Likewise, GABA A Rs were inhibited by koumine and were insensitive to humantenmine. Further assays with chimeric and mutated GlyRs showed that the extracellular domain and residues within the orthosteric site were critical for the alkaloid effects, while the pharmacophore modeling revealed the physicochemical features of the alkaloids for the functional modulation. Our study provides novel information about the molecular determinants and functional actions of four major Gelsemium indole alkaloids on inhibitory receptors, expanding our knowledge regarding the interaction of these types of compounds with protein targets of the CNS.

In Colombia, the prevalence of obesity has been increasing in recent years due to changes in dietary and nutritional patterns. While previous studies have focussed on describing obesity and its associated factors, they have mainly used a cross-sectional methodology. Accordingly, this study aims to conduct a descriptive quasi-cohort analysis to capture age-specific cohort trends in body mass index (BMI) according to sex and ethnicity (indigenous, Afro-Colombian, and the remaining population). The study utilised data from the National Survey of the Nutritional Situation in Colombia (ENSIN) conducted in 2005, 2010, and 2015 that included 214,136 individuals aged 20-64 years after screening. Data on ethnicity were only available from the 2010 and 2015 surveys. Overall, the prevalence of obesity increased by 6.1 percentage points (from 15.2% to 21.3%) between 2005 and 2015 (men from 10.4% to 15.7%; women from 18.2% to 25.7%). Among Afro-Colombians, obesity rose 6.6 percentage points (from 19.4% to 26.0%), again more so in women than in men (2015: 35.2% versus 17.8%). Among indigenous people, the proportion increased by 5.3 percentage points (from 13.5% to 18.8%), with women reporting highest rates (2015: 23.7% against 12.6% in men). Age- and cohort-specific results also indicate that recent adult cohorts are experiencing sharp increases in BMI, for example, while 25-29-year-old males born in 1975-1979 had a BMI of 24.2 kg/m 2 , among 40-44-year-olds of the same cohort, this equalled 26.8 kg/m 2 . In the case of women, these age differences in BMI among the same cohort are even greater (24.4 and 28.0 kg/m 2 ). In summary, the results of this study indicate that Colombia is still in the early stages of the obesity transition, urging the need to monitor obesity trends in Colombia from both an age and cohort perspective. To achieve this, longitudinal surveys or repeated cross-sectional surveys like the ENSIN could be utilised.

Chenopodium quinoa Willd. is a native species that originated in the High Andes plateau (Altiplano) and its cultivation spread out to the south of Chile. Because of the different edaphoclimatic characteristics of both regions, soils from Altiplano accumulated higher levels of nitrate ( NO 3 - ) than in the south of Chile, where soils favor ammonium (NH 4 + ) accumulation. To elucidate whether C. quinoa ecotypes differ in several physiological and biochemical parameters related to their capacity to assimilate NO 3 - and NH 4 + , juvenile plants of Socaire (from Altiplano) and Faro (from Lowland/South of Chile) were grown under different sources of N ( NO 3 - or NH 4 + ). Measurements of photosynthesis and foliar oxygen-isotope fractionation were carried out, together with biochemical analyses, as proxies for the analysis of plant performance or sensitivity to NH 4 + . Overall, while NH 4 + reduced the growth of Socaire, it induced higher biomass productivity and increased protein synthesis, oxygen consumption, and cytochrome oxidase activity in Faro. We discussed that ATP yield from respiration in Faro could promote protein production from assimilated NH 4 + to benefit its growth. The characterization of this differential sensitivity of both quinoa ecotypes for NH 4 + contributes to a better understanding of nutritional aspects driving plant primary productivity., 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 © 2023 Jerez, Ortiz, Castro, Escobar, Sanhueza, Del-Saz, Ribas-Carbo, Coba de la Peña, Ostria-Gallardo, Fischer, Castro and Bascunan-Godoy.)

Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly affects the elderly. AD's main features have been related to cellular and molecular events, including the aberrant aggregation of the amyloid beta peptide (Aβ), Ca 2+ dyshomeostasis, and increased mitochondria-associated membranes (MAMs). Transglutaminase type 2 (TG2) is a ubiquitous enzyme whose primary role is the Ca 2+ -dependent proteins transamidation, including the Aβ peptide. TG2 activity has been closely related to cellular damage and death. We detected increased TG2 levels in neuronal cells treated with Aβ oligomers (AβOs) and hippocampal slices from J20 mice using cellular and molecular approaches. In this work, we characterized the capacity of TG2 to interact and promote Aβ toxic aggregates (AβTG2). AβTG2 induced an acute increase in intracellular Ca 2+ , miniature currents, and hiperexcitability, consistent with an increased mitochondrial Ca 2+ overload, IP3R-VDAC tethering, and mitochondria-endoplasmic reticulum contacts (MERCs). AβTG2 also decreased neuronal viability and excitatory postsynaptic currents, reinforcing the idea of synaptic failure associated with MAMs dysregulation mediated by TG2. Z-DON treatment, TG2 inhibitor, reduced calcium overload, mitochondrial membrane potential loss, and synaptic failure, indicating an involvement of TG2 in a toxic cycle which increases Aβ aggregation, Ca 2+ overload, and MAMs upregulation. These data provide novel information regarding the role TG2 plays in synaptic function and contribute additional evidence to support the further development of TG2 inhibitors as a disease-modifying strategy for AD., Competing Interests: Conflict of interest statement None., (Copyright © 2023. Published by Elsevier Masson SAS.)

Lysolecithin might increase ruminal and intestinal emulsification, leading to increased digestibility, but there is minimum information about which is the most appropriate phase to start supplementation and its impacts on feedlot performance and muscle fatty acid profile. Two experiments were conducted to evaluate the effects of phase-feeding of Lysoforte™ eXtend (LYSO). In the first experiment, 1,760 predominantly Bos indicus bullocks (initial body weight of 400 ± 0.561 kg) were allocated in a complete randomized block design. LYSO was supplemented at 1 g/1% of ether extract from the diet. Treatments were no LYSO supplementation (NON); LYSO starting during the growing period and continuing during the finishing period; LYSO starting during the finishing period (FIN); and LYSO during adaptation, growing, and finishing periods (ALL). In the second experiment, the same treatments were evaluated with 96 bullocks (64 Nellore and 32½ Nellore × ½ Angus) in a 4 × 2 factorial arrangement (treatments × genotype). For both studies, intake and average daily gain were accessed; carcass characteristics were evaluated in the first experiment, while digestibility of nutrients and profile of muscle fatty acids were measured in the second experiment. In the first experiment, LYSO increased final body weight ( P < 0.022) and average daily gain (GRO and FIN; P < 0.05). In the second study, a treatment × breed × feeding phase interaction was observed with Nellore having a greater average daily gain ( P < 0.05) than crossbreds in every feeding phase that LYSO was introduced to the diet. A treatment × feeding phase interaction was observed for digestibility, such that LYSO increased total dry matter ( P = 0.004), crude protein ( P = 0.043), and NDF ( P = 0.001) digestibility during the finishing period. A treatment × breed × day classification was observed ( P < 0.05). During the finishing phase, crossbreds treated with LYSO had greater DMI ( P < 0.05) on very hot days than NON. Also, animals treated with LYSO presented a greater C18:3 n3 concentration ( P = 0.047) in the longissimus . Overall, feeding LYSO during GRO and FIN enhanced feedlot performance and should lead to higher intakes during very hot days of the finishing feeding period., Competing Interests: MC and LG were employed by Kemin Industries. JC and RC were consultants to Nutribeef, Inc. The remaining 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 © 2023 Pacheco, Oliveira Gusmão, Moura, Capelari, Greco, Carvalho, Cervieri, Castro, de Alencar Beserra, Campanelli, Cabral, Carvalho, Lanna, Neto, Galyean and Maia.)

"Memory imprint" refers to the process when prior exposure to stress prepares the plant for subsequent stress episodes. Seed priming is a strategy to change the performance of seedlings to cope with stress; however, mechanisms associated with the metabolic response are fragmentary. Salinity is one of the major abiotic stresses that affect crop production in arid and semiarid areas. Chenopodium quinoa Willd. (Amaranthaceae) is a promising crop to sustain food security and possesses a wide genetic diversity of salinity tolerance. To elucidate if the metabolic memory induced by seed halo-priming (HP) differs among contrasting saline tolerance plants, seeds of two ecotypes of Quinoa (Socaire from Atacama Salar, and BO78 from Chilean Coastal/lowlands) were treated with a saline solution and then germinated and grown under different saline conditions. The seed HP showed a more positive impact on the sensitive ecotype during germination and promoted changes in the metabolomic profile in both ecotypes, including a reduction in carbohydrates (starch) and organic acids (citric and succinic acid), and an increase in antioxidants (ascorbic acid and α-tocopherol) and related metabolites. These changes were linked to a further reduced level of oxidative markers (methionine sulfoxide and malondialdehyde), allowing improvements in the energy use in photosystem II under saline conditions in the salt-sensitive ecotype. In view of these results, we conclude that seed HP prompts a "metabolic imprint" related to ROS scavenger at the thylakoid level, improving further the physiological performance of the most sensitive ecotype., 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 © 2023 Cifuentes, González, Pinto-Irish, Álvarez, Coba de la Peña, Ostria-Gallardo, Franck, Fischer, Barros, Castro, Ortiz, Sanhueza, Del-Saz, Bascunan-Godoy and Castro.)

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD + ; regulating processes such as cell migration and synaptic transmission. Changes in the state of phosphorylation and/or the intracellular redox potential activate the opening of HCs in different cell types. Cxs such as Cx43 and Cx32 have been associated with proliferation and migration at different stages of CNS development. Here, using molecular and cellular biology techniques (permeability), we demonstrate the expression and functionality of HCs-Cxs, including Cx46 and Cx32, which are associated with the release of ATP during the neurulation process in Xenopus laevis . Furthermore, applications of FGF2 and/or changes in intracellular redox potentials (DTT), well known HCs-Cxs modulators, transiently regulated the ATP release in our model. Importantly, the blockade of HCs-Cxs by carbenoxolone (CBX) and enoxolone (ENX) reduced ATP release with a concomitant formation of NTDs. We propose two possible and highly conserved binding sites (N and E) in Cx46 that may mediate the pharmacological effect of CBX and ENX on the formation of NTDs. In summary, our results highlight the importance of ATP release mediated by HCs-Cxs during neurulation.

The Gelsemium elegans plant preparations have shown beneficial activity against common diseases, including chronic pain and anxiety. Nevertheless, their clinical uses are limited by their toxicity. Gelsemine, one of the most abundant alkaloids in the Gelsemium plants, have replicated these therapeutic and toxic actions in experimental behavioral models. However, the molecular targets underlying these biological effects remain unclear. The behavioral activity profile of gelsemine suggests the involvement of GABA A receptors (GABA A Rs), which are the main biological targets of benzodiazepines (BDZs), a group of drugs with anxiolytic, hypnotic, and analgesic properties. Here, we aim to define the modulation of GABA A Rs by gelsemine, with a special focus on the subtypes involved in the BDZ actions. The gelsemine actions were determined by electrophysiological recordings of recombinant GABA A Rs expressed in HEK293 cells, and of native receptors in cortical neurons. Gelsemine inhibited the agonist-evoked currents of recombinant and native receptors. The functional inhibition was not associated with the BDZ binding site. We determined in addition that gelsemine diminished the frequency of GABAergic synaptic events, likely through a presynaptic modulation. Our findings establish gelsemine as a negative modulator of GABA A Rs and of GABAergic synaptic function. These pharmacological features discard direct anxiolytic or analgesic actions of gelsemine through GABA A Rs but support a role of GABA A Rs on the alkaloid induced toxicity. On the other hand, the presynaptic effects of the alkaloid provide an additional mechanism to explain their beneficial effects. Collectively, our results contribute novel information to improve understanding of gelsemine actions in the mammalian nervous system., 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 © 2023 Marileo, Gavilán, San Martín, Lara, Sazo, Muñoz-Montesino, Castro, Burgos, Leiva-Salcedo, Aguayo, Moraga-Cid, Fuentealba and Yévenes.)

The main strategy for the treatment of epilepsy is the use of pharmacological agents known as antiseizure medication (ASM). These drugs control the seizure onset and improves the life expectancy and quality of life of patients. Several ASMs are contraindicated during pregnancy, due to a potential teratogen risk. For this reason, the pharmacological treatments of the pregnant Women with Epilepsy (WWE) need comprehensive analyses to reduce fetal risk during the first trimester of pregnancy. The mechanisms by which ASM are teratogens are still under study and scientists in the field, propose different hypotheses. One of them, which will be addressed in this review, corresponds to the potential alteration of ASM on ion channels and proteins involved in relevant signaling and cellular responses (i.e., migration, differentiation) during embryonic development. The actual information related to the action of ASM and its possible targets it is poorly understood. In this review, we will focus on describing the eventual presence of some ion channels and synaptic proteins of the neurotransmitter signaling pathways present during early neural development, which could potentially interacting as targets of ASM. This information leads to elucidate whether these drugs would have the ability to affect critical signaling during periods of neural development that in turn could explain the fetal malformations observed by the use of ASM during pregnancy., 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 Castro, Pinto-Borguero, Yévenes, Moraga-Cid and Fuentealba.)

Introduction: Bone defects hinder implant positioning. Vertical bone deficiency is the most challenging for clinical treatment, due to the high sensitivity of the technique and frequent intra- and postoperative complications. An alternative treatment for vertical defects is guided bone regeneration with simultaneous implantation; however, few studies have evaluated its effectiveness over time., Objective: To evaluate peri-implant tissue stability in a dental implant simultaneously positioned in an aesthetic zone of an area of zone vertical bone regeneration 3 years after functional load., Case Presentation: A 62-year-old male presented with the absence of the right lateral incisor and vertical bone defect of 3mm. His initial condition affected the relation of zenith points, causing disharmony. After case evaluation, vertical guided bone regeneration and simultaneous dental implants were performed to obtain a vertical bone gain of 3mm. The implant was rehabilitated with a zirconium crown and evaluated 3 years after functional loading., Conclusion: Vertical guided bone regeneration and simultaneous dental implant in the aesthetic zone in small bone defects (<4 mm) is an appropriate surgical and prosthetic technique to reduce surgical time, providing stability of peri-implant tissues even 3 years after functional implant loading., Competing Interests: Conflict of interests: The authors do not report any conflict of interest

In the midst of the health emergency caused by COVID-19 in Colombia, strategies have been generated to strengthen food security and sovereignty. Among the mechanisms adopted by urban and rural communities and local governments are alternative ways of obtaining food, one of which is trueque, which allows the exchange of food produced by peasants between territories. In Bogota, mercados campesinos have been strengthened, which have made it possible to bring food produced by peasants in Tolima, Meta and Boyacá to urban households, promoting short marketing circuits and fair payment to producers. In spite of these alternatives, the demonstrations to make visible the hunger of the households emerged the trapos rojos (red rags) in the houses, which have alerted about the situation of a good part of Colombians and have encouraged solidarity among neighbors. The position of academia has been avant-garde, directly involving peasants in processes to guarantee the right to food in Colombia.

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO 2 -sensitive vasodilatory brain mechanism with surplus of exogenous CO 2 or disruption of brain CO 2 /HCO 3 - transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO 2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO 2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity., (© 2022. The Author(s).)

The onset and mechanisms underlying neurodegenerative diseases remain uncertain. The main features of neurodegenerative diseases have been related with cellular and molecular events like neuronal loss, mitochondrial dysfunction and aberrant accumulation of misfolded proteins or peptides in specific areas of the brain. The most prevalent neurodegenerative diseases belonging to age-related pathologies are Alzheimer's disease, Huntington's disease, Parkinson's disease and amyotrophic lateral sclerosis. Interestingly, mitochondrial dysfunction has been observed to occur during the early onset of several neuropathological events associated to neurodegenerative diseases. The master regulator of mitochondrial quality control and energetic metabolism is the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Additionally, it has been observed that PGC-1α appears to be a key factor in maintaining neuronal survival and synaptic transmission. In fact, PGC-1α downregulation in different brain areas (hippocampus, substantia nigra, cortex, striatum and spinal cord) that occurs in function of neurological damage including oxidative stress, neuronal loss, and motor disorders has been seen in several animal and cellular models of neurodegenerative diseases. Current evidence indicates that PGC-1α upregulation may serve as a potent therapeutic approach against development and progression of neuronal damage. Remarkably, increasing evidence shows that PGC-1α deficient mice have neurodegenerative diseases-like features, as well as neurological abnormalities. Finally, we discuss recent studies showing novel specific PGC-1α isoforms in the central nervous system that appear to exert a key role in the age of onset of neurodegenerative diseases and have a neuroprotective function in the central nervous system, thus opening a new molecular strategy for treatment of neurodegenerative diseases. The purpose of this review is to provide an up-to-date overview of the PGC-1α role in the physiopathology of neurodegenerative diseases, as well as establish the importance of PGC-1α function in synaptic transmission and neuronal survival., Competing Interests: None

This study describes the relation of photosynthetic capacity, growth and biochemical compounds in the microalgae Porphyridium cruentum under saturated irradiance (200 μmol m -2  s -1 ) by white light (WL) and low-pressure sodium vapor lamps (SOX lamps-control) and supplemented by fluorescent lamps (FLs) with different light qualities (blue: λ max = 440 nm; green: λ max = 560 nm; and red: λ max = 660 nm). The maximum photosynthetic efficiency (F v / F m ) showed a positive correlation with the light quality by saturating light SOX in mixture with stimulating blue light than the white light (WL) at the harvest day (10 days). The production, that is maximal electron transport rate (ETR max ), and energy dissipation, that is maximal nonphotochemical quenching (NPQ max ), had the same pattern throughout the time (3-6 days) being the values higher under white light (WL) compared with SOX and SOX plus supplemented different light qualities. Total protein levels increased significantly in the presence of SOX light, while phycoerythrin (B-PE) showed significant differences under SOX+ blue light. Arachidonic acid (ARA) was higher under SOX and SOX plus supplemented different light qualities than that under WL, whereas eicosapentaenoic acid (EPA) was the reverse. The high photomorphogenic potential by SOX light shows promising application for microalgal biotechnology., (© 2021 American Society for Photobiology.)

Background: According to the 2015 National Survey of the Nutritional Situation in Colombia the prevalence of stunting in children under 5 years of age was 10.8%. In terms of region, Bogotá, presented the highest prevalence rate (13%), a figure that exceeded national records. With the collaboration of local and national government, and nongovernmental it was decided to develop a pilot study involving a public health intervention with residents of Bogotá under 1 year of age with nutritional classification by anthropometry compatible with stunting risk or stunting., Methods: Pre-experimental, before and after study that sought to determine the magnitude of the change in nutritional status through a 10 months public health nutrition intervention in children under one-year-old residing in 3 prioritized territories of Bogotá., Results: The intervention comprised 1126 children living in the following territories in Bogotá: Kennedy, San Cristóbal, and Engativá. A total of 43.3% children presented delay in height for age, and 56.7% presented risk of short stature. In the final measurement, data were obtained from 686 children, identifying that 17% of the children progressed from stunting to a stunting risk and that 4.5% recovered their growth trajectory, achieving an adequate length for their age., Conclusion: That children classified as at risk or stunting at the beginning of the intervention showed an increased probability of approaching or being in the appropriate growth trajectory according to the length-for-age indicator after the intervention.

Closed colorimetric paper disc chambers and flow-through ventilated capsules are the most employed methods of measuring rates of local cutaneous evaporative water loss in cattle. However, we do not know if these methods show a close agreement with the total rate of cutaneous evaporative water loss derived from the weighing system (i.e., the gold standard method). We therefore combined a high-precision weighing system and flow through respirometry to accurately quantify the cutaneous evaporative water loss rates in shaded heifers, while simultaneously recording parallel data obtained from a flow-through ventilated capsule, and a closed colorimetric paper disc chamber. Least square means of the local surface-specific cutaneous evaporative water loss rate (g m -2 h -1 ) derived from the colorimetric paper discs and ventilated capsules show close agreement to the total rate of surface-specific cutaneous evaporative water loss (g m -2 h -1 ) derived from the weighing method. Likewise, fitted linear regression lines also showed that they were well correlated (e.g., R 2  = 0.93 and r = 0.96 for ventilated capsule vs weighing method; and R 2  = 0.81 and r = 0.91 for colorimetric paper discs vs weighing method). However, the mean square deviation revealed various sources of disagreement between the local measurements and those derived from the weighing method, in which the local rate of cutaneous evaporative water loss derived from colorimetric paper discs showed greater deviation. In conclusion, given the importance of cutaneous evaporative water loss for assessing temperature requirements and heat tolerance of cattle, our findings show large discrepancies derived from the closed colorimetric paper discs chamber when compared with parallel data derived from the gold standard method, which is sufficient to call into question previous findings obtained by employing such methods. Moreover, the flow-through ventilated capsule appears to be the most accurate method to assess the local rate of cutaneous evaporative water loss in cattle., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

An analytical method was validated with two reference materials of polycyclic aromatic hydrocarbons in atmospheric particles. Standard reference materials (SRMs) were incorporated into the matrix of unexposed cut quartz filters. The methodology was previously designed and extraction of polycyclic aromatic hydrocarbons (PAHs) from fortified filters was based on a rapid low-cost method, for a low consumption of volume and time. The optimisation combined a low-volume Soxhlet apparatus used in hot Soxhlet mode with a quick clean-up by solid-phase extraction with special cartridges. The quantification of target compounds was performed by gas chromatography/mass spectroscopy in SIM mode. Temperatures of injector and oven program of the GC-MS were also optimised. Experimental variables of both systems were successfully optimised and validated, achieving a robust analytical methodology.

Objective: To assess whether the municipality, in Colombia, is the appropriate setting for the development of food and nutrition security policies focused on the prevention of non-communicable diseases., Methods: Through the study of diabetes and obesity prevention in Soracá (Boyacá, Colombia), an analysis of the legal provisions related to non-communicable diseases and food and nutrition security (1990-2017) was carried out. Interviews were conducted with municipal and departmental actors, based on governance., Results: The municipality has direction and leadership, institutional design, and structure, intersectorality and capacity of the municipal government to generate health policies, such as the Municipal Policy on Food and Nutrition Security, addressing non-communicable diseases from the food, nutrition and rural situation through an eco-systemic and intersectoral approach., Conclusion: The municipality is the appropriate setting for the planning of cross-sectoral strategies with clear municipal leadership in the governance framework.

Colchicine is a plant alkaloid that is widely used as a therapeutic agent. It is widely accepted that colchicine reduces the production of inflammatory mediators mainly by altering cytoskeleton dynamics due to its microtubule polymerization inhibitory activity. However, other lines of evidence have shown that colchicine exerts direct actions on the function of ion channels, which are independent of cytoskeleton alterations. Colchicine is able to modify the function of several pentameric ligand-gated ion channels, including glycine receptors (GlyRs). Previous electrophysiological studies have shown that colchicine act as an antagonist of GlyRs composed by the α 1 subunit. In addition, it was recently demonstrated that colchicine directly bind to the α 3 subunit of GlyRs. Interestingly, other studies have shown a main role of α 3 GlyRs on chronic inflammatory pain. Nevertheless, the functional effects of colchicine on the α 3 GlyR function are still unknown. Here, by using electrophysiological techniques and bioinformatics, we show that colchicine inhibited the function of the α 3 GlyRs. Colchicine elicited concentration-dependent inhibitory effects on α 3 GlyRs at micromolar range and decreased the apparent affinity for glycine. Single-channel recordings show that the colchicine inhibition is associated with a decrease in the open probability of the ion channel. Molecular docking assays suggest that colchicine preferentially bind to the orthosteric site in the closed state of the ion channel. Altogether, our results suggest that colchicine is a competitive antagonist of the α 3 GlyRs., (Copyright © 2020 Muñoz-Montesino, Burgos, Lara, Riquelme, Flaig, San Martin, Aguayo, Fuentealba, Castro, Guzmán, Yévenes and Moraga-Cid.)

Background: Early seed germination and a functional root system development during establishment are crucial attributes contributing to nutrient competence under marginal nutrient soil conditions. Chenopodium quinoa Willd (Chenopodiaceae) is a rustic crop, able to grow in marginal areas. Altiplano and Coastal/Lowlands are two representative zones of quinoa cultivation in South America with contrasting soil fertility and edaphoclimatic conditions. In the present work, we hypothesize that the ecotypes of Quinoa from Altiplano (landrace Socaire) and from Coastal/Lowland (landrace Faro) have developed differential adaptive responses in order to survive under conditions of low availability of N in their respective climatic zones of Altiplano and Lowlands. In order to understand intrinsic differences for N competence between landraces, seed metabolite profile and germinative capacity were studied. Additionally, in order to elucidate the mechanisms of N uptake and assimilation at limiting N conditions during establishment, germinated seeds of both landraces were grown at either sufficient nitrate (HN) or low nitrate (LN) supply. We studied the photosynthetic performance, protein storage, root morphometrical parameters, activity and expression of N-assimilating enzymes, and the expression of nitrate transporters of roots in plants submitted to the different treatments., Results: Seeds from Socaire landrace presented higher content of free N-related metabolites and faster seed germination rate compared to Faro landrace. Seedlings of both ecotypes presented similar physiological performance at HN supply, but at LN supply their differences were exalted. At LN, Socaire plants showed an increased root biomass (including a higher number and total length of lateral roots), a differential regulation of a nitrate transporter (a NPF6.3-like homologue) belonging to the Low Affinity Transport System (LATS), and an upregulation of a nitrate transporter (a NRT2.1-like homologue) belonging to the High Affinity nitrate Transport System (HATS) compared to Faro. These responses as a whole could be linked to a higher amount of stored proteins in leaves, associated to an enhanced photochemical performance in Altiplano plants, in comparison to Lowland quinoa plants., Conclusions: These differential characteristics of Socaire over Faro plants could involve an adaptation to enhanced nitrate uptake under the brutal unfavorable climate conditions of Altiplano.

The neurulation process is regulated by a large amount of genetic and environmental factors that determine the establishment, folding, and fusion of the neural plate to form the neural tube, which develops into the main structure of the central nervous system. A recently described factor involved in this process is glutamate. Through NMDA ionotropic receptor, glutamate modifies intracellular Ca 2+ dynamics allowing the oriented cell migration and proliferation, essentials processes in neurulation. Glutamate synthesis depends on the mitochondrial enzyme known as glutaminase 1 (GLS1) that is widely expressed in brain and kidney. The participation of GLS 1 in prenatal neurogenic processes and in the adult brain has been experimentally established, however, its participation in early stages of embryonic development has not been described. The present investigation describes for the first time the presence and functionality of GLS1 in Xenopus laevis embryos during neurulation. Although protein expression levels remains constant, the catalytic activity of GLS1 increases significantly (~66%) between early (stage 12) and middle to late (stages 14-19) neurulation process. Additionally, the use of 6-diazo-5-oxo-L-norleucine (L-DON, competitive inhibitor of glutamine-depend enzymes), reduced significantly the GLS1 specific activity during neurulation (~36%) and induce the occurrence of neural tube defects involving its possible participation in the neural tube closure in Xenopus laevis embryos., (Copyright © 2020 Benavides-Rivas, Tovar, Zúñiga, Pinto-Borguero, Retamal, Yévenes, Moraga-Cid, Fuentealba, Guzmán, Coddou, Bascuñán-Godoy and Castro.)

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment that increasingly afflicts the elderly population. Soluble oligomers (AβOs) has been implicated in AD pathogenesis: however, the molecular events underlying a role for Aβ are not well understood. We studied the effects of AβOs on mitochondrial function and on key proteins that regulate mitochondrial dynamics and biogenesis in hippocampal neurons and PC-12 cells. We find that AβOs treatment caused a reduction in total Mfn1 after a 2 h exposure (42 ± 11%); while DRP1 increased at 1 and 2 h (205 ± 22% and 198 ± 27%, respectively), correlating to changes in mitochondrial morphology. We also observed that SIRT1 levels were reduced after acute and chronic AβOs treatment (68 ± 7% and 77 ± 6%, respectively); while PGC-1α levels were reduced with the same time treatments (68 ± 8% and 67 ± 7%, respectively). Interestingly, we found that chronic treatment with AβOs increased the levels of pSIRT1 (24 h: 157 ± 18%), and we observed changes in the PGC-1α and p-SIRT1 nucleus/cytosol ratio and SIRT1-PGC-1α interaction pattern after chronic exposure to AβOs. Our data suggest that AβOs induce important changes in the level and localization of mitochondrial proteins related with the loss of mitochondrial function that are mediated by a fast and sustained SIRT1/PGC-1α complex disruption promoting a "non-return point" to an irreversible synaptic failure and neuronal network disconnection., (Copyright © 2020 Panes, Godoy, Silva-Grecchi, Celis, Ramirez-Molina, Gavilan, Muñoz-Montecino, Castro, Moraga-Cid, Yévenes, Guzmán, Salisbury, Trushina and Fuentealba.)

Background: The 2017 American College of Cardiology and American Heart Association guideline defined hypertension as blood pressure (BP) ≥ 130/80 mmHg compared to the traditional definition of ≥140/90 mmHg. This change raised much controversy. We conducted this study to compare the impact of tight (TBPC) versus standard BP control (SBPC) on the incidence of myocardial infarction (MI) and stroke., Methods: We retrospectively identified all hypertensive patients in an ambulatory setting based on the diagnostic code for 1 year at our institution who were classified by the range of BP across 3 years into 2 groups of TBPC (< 130 mmHg) and SBPC (130-139 mmHg). We compared the incidence of new MI and stroke between the 2 groups across a 2-year follow-up. Multivariate analysis was done to identify independent predictors for the incidence of new MI and stroke., Results: Of 5640 study patients, the TBPC group showed significantly less incidence of stroke compared to the SBPC group (1.5% vs. 2.7%, P < 0.010). No differences were found in MI incidence between the 2 groups (0.6% vs. 0.8%, P = 0.476). Multivariate analysis showed that increased age independently increased the incidence of both MI (OR 1.518, 95% CI 1.038-2.219) and stroke (OR 1.876, 95% CI 1.474-2.387), and TBPC independently decreased the incidence of stroke (OR 0.583, 95% CI 0.374-0.910) but not of MI., Conclusions: Our observational study suggests that TBPC may be beneficial in less stroke incidence compared to SBPC but it didn't seem to affect the incidence of MI. Our study is limited by its retrospective design with potential confounders.

Inherent and acquired factors determine the integrated autonomic response to cardiovascular stressors. Excessive sympathoexcitation to ischemic stress is a major contributor to the potential for sudden cardiac death. To define fundamental aspects of cardiac-related autonomic neural network interactions within the thoracic cord, specifically as related to modulating sympathetic preganglionic (SPN) neural activity. Adult, anesthetized Yorkshire pigs ( n = 10) were implanted with penetrating high-density microarrays (64 electrodes) at the T2 level of the thoracic spinal cord to record extracellular potentials concurrently from left-sided dorsal horn (DH) and SPN neurons. Electrical stimulation of the T2 paravertebral chain allowed for antidromic identification of SPNs located in the intermediolateral cell column (57 of total 1,760 recorded neurons). Cardiac stressors included epicardial touch, occlusion of great vessels to transiently alter preload/afterload, and transient occlusion of the left anterior descending coronary artery (LAD). Spatial/temporal assessment of network interactions was characterized by cross-correlation analysis. While some DH neurons responded solely to changes in preload/afterload (8.5 ± 1.9%) or ischemic stress (10.5 ± 3.9%), the majority of cardiovascular-related DH neurons were multimodal (30.2 ± 4.7%) with ischemia sensitivity being one of the modalities (26.1 ± 4.7%). The sympathoexcitation associated with transient LAD occlusion was associated with increased correlations from baseline within DH neurons (2.43 ± 0.61 to 7.30 ± 1.84%, P = 0.04) and between SPN to DH neurons (1.32 ± 0.78 to 7.24 ± 1.84%, P = 0.02). DH to SPN network correlations were reduced during great vessel occlusion. In conclusion, increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation. NEW & NOTEWORTHY In an in vivo pig model, we demonstrate using novel high-resolution neural electrode arrays that increased intrasegmental network coherence within the thoracic spinal cord contributes to myocardial ischemia-induced sympathoexcitation.

Glycine receptors (GlyRs) are anion-permeable pentameric ligand-gated ion channels (pLGICs). The GlyR activation is critical for the control of key neurophysiological functions, such as motor coordination, respiratory control, muscle tone and pain processing. The relevance of the GlyR function is further highlighted by the presence of abnormal glycinergic inhibition in many pathophysiological states, such as hyperekplexia, epilepsy, autism and chronic pain. In this context, previous studies have shown that the functional inhibition of  GlyRs containing the α3 subunit is a pivotal mechanism of pain hypersensitivity. This pathway involves the activation of EP2 receptors and the subsequent PKA-dependent phosphorylation of α3GlyRs within the intracellular domain (ICD), which decrease the GlyR-associated currents and enhance neuronal excitability. Despite the importance of this mechanism of glycinergic dis-inhibition associated with dysfunctional α3GlyRs, our current understanding of the molecular events involved is limited. Here, we report that the activation of PKA signaling pathway decreases the unitary conductance of α3GlyRs. We show in addition that the substitution of the PKA-targeted serine with a negatively charged residue within the ICD of α3GlyRs and of chimeric receptors combining bacterial GLIC and α3GlyR was sufficient to generate receptors with reduced conductance. Thus, our findings reveal a potential biophysical mechanism of glycinergic dis-inhibition and suggest that post-translational modifications of the ICD, such as phosphorylation, may shape the conductance of other pLGICs.

Introduction: Upper limb movements are affected frequently by brain ischemia (BI). Mechanisms involved in recovery and compensatory movements have developed several studies. However, less attention is given to skeletal muscles, where neuromuscular junction (NMJ) has an important role on muscle tropism and functional performance., Methods: Animals were divided into two groups: control (C) and BI. Then, animals were skilled to perform single-pellet retrieval task, following these procedures: habituation, shaping, and single-pellet retrieval task. BI was induced using stereotaxic surgery in order to apply endothelin-1 in motor cortex, representative of movements of dominant paw. Reaching task performance was evaluated by single-pellet retrieval task 1 day before BI induction, 4 and 15 days after BI induction. After that, biceps, triceps, fingers flexor, and extensor muscles were extracted. NMJ was assessed in morphometric characteristics (total area, total perimeter, and feret). Muscle fiber cross-sectional area and connective tissue percentage were also evaluated for characterization. Student's t test was used for comparisons between C and BI groups. Tau Kendall's correlation was applied among variables from BI group., Results: An increase in all NMJ morphometric parameters, as well as increase of atrophy and fibrosis in BI group compared with C. There was a high level of direct correlation between mean values of NMJ morphometry with percentage of success in reaching task in BI group., Conclusion: Brain ischemia-induced NMJ compensatory expansion, muscle atrophy, and fibrosis in forelimb muscles that are related to reaching performance., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Glycine receptors (GlyRs) are members of the pentameric ligand-gated ionic channel family (pLGICs) and mediate fast inhibitory neurotransmission in the brain stem and spinal cord. The function of GlyRs can be modulated by positive allosteric modulators (PAMs). So far, it is largely accepted that both the extracellular (ECD) and transmembrane (TMD) domains constitute the primary target for many of these PAMs. On the other hand, the contribution of the intracellular domain (ICD) to the PAM effects on GlyRs remains poorly understood. To gain insight about the role of the ICD in the pharmacology of GlyRs, we examined the contribution of each domain using a chimeric receptor. Two chimeras were generated, one consisting of the ECD of the prokaryotic homologue Gloeobacter violaceus ligand-gated ion channel (GLIC) fused to the TMD of the human α 1 GlyR lacking the ICD (Lily) and a second with the ICD (Lily-ICD). The sensitivity to PAMs of both chimeric receptors was studied using electrophysiological techniques. The Lily receptor showed a significant decrease in the sensitivity to four recognized PAMs. Remarkably, the incorporation of the ICD into the Lily background was sufficient to restore the wild-type α 1 GlyR sensitivity to these PAMs. Based on these data, we can suggest that the ICD is necessary to form a pLGIC having full sensitivity to positive allosteric modulators.

Glycine receptors (GlyRs) are chloride-permeable pentameric ligand-gated ion channels. The inhibitory activity of GlyRs is essential for many physiological processes, such as motor control and respiration. In addition, several pathological states, such as hyperekplexia, epilepsy, and chronic pain, are associated with abnormal glycinergic inhibition. Recent studies have pointed out that positive allosteric modulators targeting the GlyR α3 subunit (α3GlyR) displayed beneficial effects in chronic pain models. Interestingly, previous electrophysiological studies have shown that tropeines, which are a family of synthetic antagonists of the serotonin type 3 receptors (5-HT 3 Rs), potentiate the activity of GlyRs conformed by α1 subunits. However, despite its importance as a pharmacological target in chronic pain, it is currently unknown whether the α3GlyR function is modulated by tropeines. Using electrophysiological techniques and molecular docking simulations, here we show that tropeines are inhibitors of the α3GlyR function. Tropisetron, a prototypical tropeine, exerted concentration-dependent inhibitory effects on α3GlyRs at the low micromolar range. In addition, three other tropeines showed similar effects. Single-channel recordings show that tropisetron inhibition is associated with a decrease in the open probability of the ion channel. Molecular docking assays suggest that tropeines preferentially bind to an agonist-free, closed state of the ion channel. The tropeine binding occurs in a discrete pocket around the vicinity of the orthosteric site within the extracellular domain of α3GlyR. Thus, our results describe the pharmacological modulation of tropeines on α3GlyRs. These findings may contribute to the development of GlyR-selective tropeine derivatives for basic and/or clinical applications.

Alzheimer's disease (AD) is a neurodegenerative pathology, which is characterized by progressive and irreversible cognitive impairment. Most of the neuronal perturbations described in AD can be associated with soluble amyloid- β oligomers (SO-Aβ). There is a large amount of evidence demonstrating the neuroprotective effect of Nicotine neurotransmission in AD, mainly through nicotinic acetylcholine receptor (nAChR) activation and antiapoptotic PI3K/Akt/Bcl-2 pathway signaling. Using HPLC and GC/MS, we isolated and characterized two alkaloids obtained from C. scoparius, Lupanine (Lup), and 17- oxo-sparteine (17- ox), and examined their neuroprotective properties in a cellular model of SO-Aβ toxicity. Our results showed that Lup and 17- ox (both at 0.03μM) prevented SO-Aβ-induced toxicity in PC12 cells (Lup: 64±7%; 17- ox: 57±6%). Similar results were seen in hippocampal neurons where these alkaloids prevented SO-Aβ neurotoxicity (Lup: 57±2%; 17- ox: 52±3%) and increased the frequency of spontaneous calcium transients (Lup: 60±4%; 17- Ox: 40±3%), suggesting an enhancing effect on neural network activity and synaptic activity potentiation. All of the neuroprotective effects elicited by both alkaloids were completely blocked by α-bungarotoxin. Additionally, we observed that the presence of both Lup and 17- ox increased Akt phosphorylation levels (52±4% and 35±7%, respectively) in cells treated with SO-Aβ (3 h). Taken together, our results suggest that the activation of nAChR by Lup and 17- ox induces neuroprotection in different cellular models, and appears to be an interesting target for the development of new pharmacological tools and strategies against AD.

Objectives: To determine the cost-effectiveness ratio of different courses of action for the diagnosis of Duchenne or Becker muscular dystrophy in Colombia., Methods: The cost-effectiveness analysis was performed from the Colombian health system perspective. Decision trees were constructed, and different courses of action were compared considering the following tests: immunohistochemistry (IHC), Western blot (WB), multiplex polymerase chain reaction, multiplex ligation-dependent probe amplification (MLPA), and the complete sequencing of the dystrophin gene. The time horizon matched the duration of sample extraction and analysis. Transition probabilities were obtained from a systematic review. Costs were constructed with a type-case methodology using the consensus of experts and the valuation of resources from consulting laboratories and the 2001 Social Security Institute cost manual. Deterministic sensitivity and scenario analyses were performed with one or more unavailable alternatives. Costs were converted from Colombian pesos to US dollars using the 2014 exchange rate., Results: In the base case, WB was the dominant strategy, with a cost of US $419.07 and a sensitivity of 100%. This approach remains the dominant strategy down to a 98.2% sensitivity and while costs do not exceed US $837.38. If WB was not available, IHC had the best cost-effectiveness ratio, followed by MLPA and sequencing., Conclusions: WB is a cost-effective alternative for the diagnosis of patients suspected of having Duchenne or Becker muscular dystrophy in the Colombian health system. The IHC test is rated as the second-best detection method. If these tests are not available, MLPA followed by sequencing would be the most cost-effective alternative., (Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Failure of neural tube closure leads to neural tube defects (NTDs), which can have serious neurological consequences or be lethal. Use of antiepileptic drugs (AEDs) during pregnancy increases the incidence of NTDs in offspring by unknown mechanisms. Here we show that during Xenopus laevis neural tube formation, neural plate cells exhibit spontaneous calcium dynamics that are partially mediated by glutamate signaling. We demonstrate that NMDA receptors are important for the formation of the neural tube and that the loss of their function induces an increase in neural plate cell proliferation and impairs neural cell migration, which result in NTDs. We present evidence that the AED valproic acid perturbs glutamate signaling, leading to NTDs that are rescued with varied efficacy by preventing DNA synthesis, activating NMDA receptors, or recruiting the NMDA receptor target ERK1/2. These findings may prompt mechanistic identification of AEDs that do not interfere with neural tube formation. SIGNIFICANCE STATEMENT Neural tube defects are one of the most common birth defects. Clinical investigations have determined that the use of antiepileptic drugs during pregnancy increases the incidence of these defects in the offspring by unknown mechanisms. This study discovers that glutamate signaling regulates neural plate cell proliferation and oriented migration and is necessary for neural tube formation. We demonstrate that the widely used antiepileptic drug valproic acid interferes with glutamate signaling and consequently induces neural tube defects, challenging the current hypotheses arguing that they are side effects of this antiepileptic drug that cause the increased incidence of these defects. Understanding the mechanisms of neurotransmitter signaling during neural tube formation may contribute to the identification and development of antiepileptic drugs that are safer during pregnancy., (Copyright © 2018 the authors 0270-6474/18/384762-12$15.00/0.)

Background: Studies indicate high rates of criminal behavior, violent activities, and legal problems among illicit drug users (IDU) in Brazil. The aim of this study was to estimate the prevalence and factors associated with criminal behavior among IDU undergoing treatment for chemical dependency in Central Brazil., Methods: Cross-sectional study carried out with IDU undergoing treatment for chemical dependence. Data were collected by means of face-to-face interviews and analyzed using logistic regression., Results: Of the total participants (n = 274), 46.7%, 15.7%, and 10.9% reported involvement in robbery, drug trafficking and homicide, respectively. Robbery was associated with young age, withdrawal symptoms, prison record, sex work, and crack use, while drug trafficking was associated with young age, low education, and marijuana use. Homicides were associated with cocaine and marijuana use., Conclusion: The results show high rates of criminal behavior among drug users, demonstrating associations between socio-demographic and behavioral characteristics, illicit drug use, and practices of illegal activities. These variables must be considered when planning programs and policies to reduce harm related to drug use and abuse.

Objective: Estimate the prevalence and determinants of tobacco use by students., Methods: This cross-sectional study, carried out between 2013 and 2014, evaluates 701 public school students between 10 and 79 years of age living in a city in the countryside of the State of Goias, Midwest of Brazil. A structured questionnaire collected the data and the predictor variables were demographic data, family nucleus, religion, physical activity practice, family functionality and parental smoking. Two multivariable models were implemented, the first for occasional tobacco use and the second for regular use, acquiring the measure of prevalence ratio (PR) and their respective 95%CI. Variables with p < 0.10 were included in Poisson regression models with robust variance to obtain the adjusted PR (adPR) and 95%CI. The Wald Chi-Squared test examined the differences between proportions, and values with p < 0.05 were statistically significant., Results: The prevalence of occasional and regular tobacco use were 33.4% (95%CI 29.8-36.9) and 6.7% (95%CI 5.0-8.8), respectively. The factors associated with occasional tobacco consumption were age of 15 to 17 years (adPR = 1.98) and above 18 years (adPR = 3.87), male gender (adPR = 1.23), moderate family dysfunction (adPR = 1.30), high family dysfunction (adPR = 1.97) and parental smoking (adPR = 1.60). In regards to regular consumption of tobacco, age above 18 years (adPR = 4.63), lack of religion (adPR = 2.08), high family dysfunction (adPR = 2.35) and parental smoking (adPR = 2.89) remained associated., Conclusions: Students exhibit a high prevalence of occasional and regular tobacco use. This consumption relates to sociodemographic variables and family dysfunction., Objetivo: Estimar a prevalência e determinantes do consumo de tabaco por estudantes., Métodos: Neste estudo de corte transversal, realizado entre 2013 e 2014, avaliamos 701 estudantes entre 10 e 79 anos de escolas públicas de um município do interior do estado de Goiás, Centro-Oeste do Brasil. Os dados foram coletados por meio de um questionário estruturado, cujas variáveis preditoras foram: dados sociodemográficos, núcleo familiar, religião, prática de atividade física, funcionalidade familiar e pai ou mãe fumante. Foram implementados dois modelos multivariáveis, o primeiro para uso de tabaco na vida e o segundo para uso regular, obtendo-se como medida de efeito razão de prevalência (RP) e seus respectivos IC95%. Variáveis com p < 0,10 foram incluídas em modelos de regressão de Poisson com variância robusta, para obtenção da RP ajustada (RPaj) e IC95%. O teste Qui-quadrado de Wald foi utilizado para testar as diferenças entre as proporções, e valores com p < 0,05 foram considerados estatisticamente significantes., Resultados: As prevalências de consumo de tabaco na vida e regular foram de 33,4% (IC95% 29,8-36,9) e 6,7% (IC95% 5,0-8,8), respectivamente. Os fatores associados ao consumo de tabaco na vida foram: idade de 15 a 17 anos (RPaj = 1,98) e superior a 18 anos (RPaj = 3,87), sexo masculino (RPaj = 1,23), moderada disfuncionalidade familiar (RPaj = 1,30), elevada disfuncionalidade familiar (RPaj = 1,97) e pai ou mãe fumante (RPaj = 1,60). Em relação ao consumo regular de tabaco, permaneceram associados a idade superior a 18 anos (RPaj = 4,63), não possuir religião (RPaj = 2,08), elevada disfuncionalidade familiar (RPaj = 2,35) e pai ou mãe fumante (RPaj = 2,89)., Conclusões: Estudantes apresentam elevada prevalência de consumo de tabaco na vida e regular. Esse consumo associa-se com variáveis sociodemográficas e disfuncionalidade familiar.

Objective: Investigate patterns and factors associated with tobacco consumption among residents of a rural settlement., Methods: A cross-sectional study conducted between September and November 2014, with 172 residents of a rural settlement in the Midwest region of Brazil. We analyzed as dependent variables tobacco consumption at some point in life; current tobacco consumption; tobacco abuse; and the high risk of nicotine dependence, with sociodemographic variables associated with tobacco use, and we applied the Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST) and Self-Reporting Questionnaire (SRQ-20)., Results: The prevalence of tobacco use in life, current use, tobacco abuse, and high risk of nicotine dependence were 62.2%, 20.9%, 59.8%, and 10.3%, respectively. Advanced age, low education level, evangelical religion, marijuana use, hypnotic or sedative consumption, and male gender were factors associated with smoking patterns in the settlers., Conclusions: There was a high prevalence of smoking patterns, evidencing the need for public policies on tobacco prevention and control in this population.

The literature is very sparse regarding research on the thermal equilibrium in Guzerat cattle (Bos indicus) under field conditions. Some factors can modify the physiological response of Guzerat cattle, such as the reactivity of these animals to handling. Thus, the development of a methodology to condition and select Guzerat cattle to acclimate them to the routine collection of data without altering their physiological response was the objective of the preliminary experiment. Furthermore, the animals selected were used in the main experiment to determine their thermal equilibrium according to the thermal environment. For this proposal, the metabolic heat production and heat exchange between the animal and the environment were measured simultaneously in the field with an indirect calorimetry system coupled to a facial mask. The results of the preliminary experiment showed that the respiratory rate could demonstrate that conditioning efficiently reduced the reactivity of the animals to experimental handling. Furthermore, the respiratory rate can be used to select animals with less reactivity. The results of the main experiment demonstrate that the skin, hair-coat surface and expired air temperature depend on the air temperature, whereas the rectal temperature depends on the time of day; consequently, the sensible heat flow was substantially reduced from 70 to 20Wm(-2) when the air temperature increased from 24 to 34°C. However, the respiratory latent heat flow increased from 10 to 15Wm(-2) with the same temperature increase. Furthermore, the metabolic heat production remained stable, independent of the variation of the air temperature; however, it was higher in males than in females (by approximately 25%). This fact can be explained by the variation of the ventilation rate, which had a mean value of 1.6 and 2.2Ls(-1) for females and males, respectively., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In recent years there has been an increase in the understanding of ethanol actions on the type A γ-aminobutyric acid chloride channel (GABAAR), a member of the pentameric ligand gated ion channels (pLGICs). However, the mechanism by which ethanol potentiates the complex is still not fully understood and a number of publications have shown contradictory results. Thus many questions still remain unresolved requiring further studies for a better comprehension of this effect. The present review concentrates on the involvement of GABAAR in the acute actions of ethanol and specifically focuses on the immediate, direct or indirect, synaptic and extra-synaptic modulatory effects. To elaborate on the immediate, direct modulation of GABAAR by acute ethanol exposure, electrophysiological studies investigating the importance of different subunits, and data from receptor mutants will be examined. We will also discuss the nature of the putative binding sites for ethanol based on structural data obtained from other members of the pLGICs family. Finally, we will briefly highlight the glycine gated chloride channel (GlyR), another member of the pLGIC family, as a suitable target for the development of new pharmacological tools.

Nervous system development relies on the generation of neurons, their differentiation and establishment of synaptic connections. These events exhibit remarkable plasticity and are regulated by many developmental cues. Here, we review the mechanisms of three classes of these cues: morphogenetic proteins, electrical activity, and the environment. We focus on second messenger dynamics and their role as integrators of the action of diverse cues, enabling plasticity in the process of neural development., (© 2014 Wiley Periodicals, Inc.)

The α1-subunit containing glycine receptors (GlyRs) is potentiated by ethanol, in part, by intracellular Gβγ actions. Previous studies have suggested that molecular requirements in the large intracellular domain are involved; however, the lack of structural data about this region has made it difficult to describe a detailed mechanism. Using circular dichroism and molecular modeling, we generated a full model of the α1-GlyR, which includes the large intracellular domain and provides new information on structural requirements for allosteric modulation by ethanol and Gβγ. The data strongly suggest the existence of an α-helical conformation in the regions near transmembrane (TM)-3 and TM4 of the large intracellular domain. The secondary structure in the N-terminal region of the large intracellular domain near TM3 appeared critical for ethanol action, and this was tested using the homologous domain of the γ2-subunit of the GABAA receptor predicted to have little helical conformation. This region of γ2 was able to bind Gβγ and form a functional channel when combined with α1-GlyR, but it was not sensitive to ethanol. Mutations in the N- and C-terminal regions introduced to replace corresponding amino acids of the α1-GlyR sequence restored the ability to be modulated by ethanol and Gβγ. Recovery of the sensitivity to ethanol was associated with the existence of a helical conformation similar to α1-GlyR, thus being an essential secondary structural requirement for GlyR modulation by ethanol and G protein., (Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.)

Extracellular and intracellular copper and zinc regulate synaptic activity and plasticity, which may impact brain functionality and human behavior. We have found that a metal coordinating molecule, Neocuproine, transiently increases free intracellular copper and zinc levels (i.e., min) in hippocampal neurons as monitored by Phen Green and FluoZin-3 fluorescence, respectively. The changes in free intracellular zinc induced by Neocuproine were abolished by the presence of a non-permeant copper chelator, Bathocuproine (BC), indicating that copper influx is needed for the action of Neocuproine on intracellular Zn levels. Moreover, Neocuproine decreased the mRNA levels of Synapsin and Dynamin, and did not affect the expression of Bassoon, tubulin or superoxide dismutase (SOD). Western blot analysis showed that protein levels of synapsin and dynamin were also down regulated in the presence of Neocuproine and that these changes were accompanied by a decrease in calcium transients and neuronal activity. Furthermore, Neocuproine decreased the number of active neurons, effect that was blocked by the presence of BC, indicating that copper influx is needed for the action of Neocuproine. We finally show that Neocuproine blocks the epileptiform-like activity induced by bicuculline in hippocampal neurons. Collectively, our data indicates that presynaptic protein configuration and function of primary hippocampal neurons is sensitive to transient changes in transition metal homeostasis. Therefore, small molecules able to coordinate transition metals and penetrate the blood-brain barrier might modify neurotransmission at the Central Nervous System (CNS). This might be useful to establish therapeutic approaches to control the neuronal hyperexcitabiltity observed in brain conditions that are associated to copper dyshomeotasis such as Alzheimer's and Menkes diseases. Our work also opens a new avenue to find novel and effective antiepilepsy drugs based in metal coordinating molecules.

The objective of this study was to evaluate the perception of the elderly residents of a long-stay nursing home on the process of institutionalization. We interviewed 14 subjects, five women and nine men, aged between 60 and 92 years. Data collection was conducted with a semi-structured sociodemographic interview, which presented the guiding question: "Tell me about how is your life, what do you do and how did you come to live here". From the analysis, we found topics related to feelings of abandonment, loneliness, anger, ingratitude, living with chronic pain, satisfaction of property in the nursing home, productivity and social relationship. Given the thematic analysis, it was possible to group them into three categories such as: what the elderly feel, what the elderly perceive and what the elderly desire. As a result, we need public policies that addresses to the service provided by institutions regarding elderly expectations.

Ethanol alters the function of several members of the Cys-loop ligand-gated ion channel superfamily. Recent studies have shown that the sensitivity of the α1 glycine receptor (GlyR) to ethanol can be affected by the state of G protein activation mediated by the interaction of Gβγ with intracellular amino acids in the GlyR. Here, we evaluated the physicochemical property of Lys385 that contributes to ethanol modulation by using mutagenesis, patch-clamp, and biochemical techniques. A conserved substitution (K385R) did not affect either the apparent glycine EC₅₀ (40 ± 1 versus 41 ± 0.5 μM) or the ethanol-induced potentiation (53 ± 5 versus 46 ± 5%) of the human α1 GlyR. On the other hand, replacement of this residue with glutamic acid (K385E), an acidic amino acid, reduced the potentiation of the GlyR to 10 ± 1%. Furthermore, mutations with a hydrophobic leucine (K385L), a hydrogen bond donor glutamine (K385Q), or a neutral residue (K385A) also reduced ethanol modulation. Finally, substitution by a large and hydrophobic residue (K385F) and deletion of 385 (Lys385&#95;) reduced ethanol modulation to 10 ± 4 and 17 ± 0.4%, respectively. Experiments using dynamic cysteine substitution with a methanethiosulfonate reagent and homology modeling indicate that the basic property and the position of Lys385, probably because of its interaction with Gβγ, is critical for ethanol potentiation of the receptor.

One factor conditioning quinoa (Chenopodium quinoa Willd.) adoption is the need to increase yield. This paper analyses the effect that Paclobutrazol, a GA synthesis inhibitor, produces on yield, biomass, partitioning, seed number and weight in quinoa. Two experiments were conducted under field conditions: one compared a tall genotype (2-Want) with a shorter genotype (NL-6); while the other analysed seed yield and its components using the 2-Want genotype. As a consequence of Paclobutrazol application in the one-genotype experiment, plant height decreased from 197 to 138cm, yield increased from 517 to 791gm-2, seed numbers rose from 308000 to 432000seedsperm2, and the harvest index increased from 0.282 to 0.398gg-1. Biomass accumulation and seed weight were not affected. The leaf area index was reduced by Paclobutrazol but radiation interception was only marginally reduced; soil plant analysis development (SPAD) values and specific leaf weight were increased, but radiation use efficiency was not affected by treatments. Root biomass and lateral roots tended to increase under Paclobutrazol treatment. Genotypes were compared until the end of flowering and similar responses were obtained. Higher yields could be obtained in quinoa if reproductive partitioning was increased, turning it into a good candidate in the search for high quality protein sources.

Background: Sedation for heart catheterization has been a cause for concern. Benzodiazepines, alpha-2 adrenergic agonists and opioids are used for this purpose. However, each drug has advantages and disadvantages., Objective: To evaluate the efficacy of sufentanil and clonidine as sedative in patients undergoing heart catheterization, observing their impact on hemodynamic and respiratory parameters, the presence of side effects and satisfaction of the patient and interventional cardiologist with the examination., Methods: This is a prospective, double-blind, randomized and controlled clinical trial involving 60 patients who received 0.1 µg/kg of sufentanil or 0.5 µg/kg of clonidine before heart catheterization. The score of sedation according to the Ramsay scale, the need for use of midazolam, side effects and hemodynamic and respiratory parameters were recorded, with the data being analyzed at 06 different moments., Results: The behavior of blood pressure, heart rate and respiratory rate was similar in both groups, but, at moment 2, the patients in the sufentanil group (Group S) had a lower sedation score on the Ramsay scale, and the peripheral oxyhemoglobin saturation was lower than in the clonidine group (Group C) at time 6. Patients in Group S had higher incidence of nausea and vomiting after surgery than patients in Group C. Patient satisfaction was higher in the clonidine group. The interventional cardiologists were satisfied in both groups., Conclusion: Sufentanil and clonidine were effective as sedative in patients undergoing heart catheterization.