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Se aislaron, identificaron y caracterizaron 20 cepas de bacterias ácido lácticas (BAL) de un “queso crema tropical” tradicionalmente fabricado con leche bronca. Las 20 cepas de BAL utilizadas crecieron en leche descremada y cada una de ellas fue evaluada mediante su poder acidificante (pH) en cuatro tiempos de incubación (6, 24, 48 y 72 h) y tres temperaturas de fermentación (30, 37 y 42oC). En base al pH más bajo, se seleccionaron seis cepas para fabricar un “queso tipo crema tropical” con leche pasteurizada. Las cepas fueron caracterizadas mediante pruebas bioquímicas (fermentación de carbohidratos y producción de amonio a partir de arginina) y de secuenciación del 16S rDNA. Se identificaron cinco especies de Lactobacillus fermentum y una especie de Lactobacillus pentosus. Entre las temperaturas de fermentación y el tiempo de incubación se estimaron diferencias significativas (p < 0.05) en cada una de las cepas. En las temperaturas de 37oC y 42oC se produjeron los valores de pH más bajos a las 72 horas de incubación. Además, el ácido láctico, ácido acético, ácido propiónico y ácido butírico en leche fermentada se evaluaron con cada cepa y no hubo diferencias significativas en los niveles de producción de dichos metabolitos (p > 0.05). Asimismo, se realizaron pruebas que incluyeron cuentas totales de flora no láctica, cuenta de BAL, coliformes totales, Escherichia coli, hongos y levaduras en el queso crema elaborado con leche pasteurizada y como referencia se uso al queso crema artesanal.

El objetivo de este estudio fue evaluar la respuesta en cambio de peso vivo de toretes pastoreando estrella africana (Cynodon plectostachyus) y suplementados con bloque multinutricional en condiciones tropicales mexicanas, durante 90 d. Se utilizaron 30 toretes con peso inicial promedio de 360 ± 30 kg, alojados en tres grupos de 10, asignados aleatoriamente a los tratamientos: 1) pastoreo + bloque multinutricional, 2) pastoreo + suplemento tradicional y 3) pastoreo solo, en un diseño completamente al azar. El pastoreo rotacional tuvo tres días de ocupación y 27 d de descanso. El forraje ofrecido promedio fue 5 312 kg materia seca (MS) ha-1; proteína cruda (PC), 6.8 %; fibra detergente neutro (FDN), 74.0 %; fibra detergente acido (FDA), 51.9 %; y digestibilidad in situ 38.5 %. El consumo total de materia seca fue mayor (p < 0.01) en tratamiento tres (14.4 kg MS animal-1 d-1) comparado con los tratamientos uno y dos (10.7 kg y 13.4 kg MS animal-1 d-1, respectivamente). Contrario a lo esperado, la ganancia diaria de peso fue similar (p > 0.05) entre tratamientos, promediando 0.43 kg animal-1 d-1. Este comportamiento fue debido principalmente a que el bloque multinutricional no incrementó la tasa de degradación del forraje ni la producción de ácidos grasos volátiles (AGVs) en el rumen. Bajo las condiciones del presente estudio, suplementar con bloque multinutricional a toretes en pastoreo, no representó ningún beneficio.

IntroductionThe COVID-19 pandemic disrupted the preventive services for cervical cancer (CC) control programs in Mexico, which will result in increased mortality. This study aims to assess the impact of the pandemic on the interruption of three preventive actions in the CC prevention program in Mexico.MethodsThis study is a retrospective time series analysis based on administrative records for the uninsured population served by the Mexican Ministry of Health. Patient data were retrieved from the outpatient service information system and the hospital discharge database for the period 2017–2021. Data were aggregated by month, distinguishing a pre-pandemic and a pandemic period, considering April 2020 as the start date of the pandemic. A Poisson time series analysis was used to model seasonal and secular trends. Five process indicators were selected to assess the disruption of the CC program, these were analyzed as monthly data (N=39 pre-pandemic, N=21 during the pandemic). HPV vaccination indicators (number of doses and coverage) and diagnostic characteristics of CC cases were analyzed descriptively. The time elapsed between diagnosis and treatment initiation in CC cases was modeled using restricted cubic splines from robust regression.ResultsAnnual HPV vaccination coverage declined dramatically after 2019 and was almost null in 2021. The number of positive Papanicolaou smears decreased by 67.8% (90%CI: -72.3, -61.7) in April–December 2020, compared to their expected values without the pandemic. The immediate pandemic shock (April 2020) in the number of first-time and recurrent colposcopies was -80.5% (95%CI:−83.5, −77.0) and -77.9% (95%CI: −81.0, −74.4), respectively. An increasing trend was observed in the proportion of advanced stage and metastatic CC cases. The fraction of CC cases that did not receive medical treatment or surgery increased, as well as CC cases that received late treatment after diagnosis.ConclusionsOur analyses show significant impact of the COVID-19 pandemic with declines at all levels of CC prevention and increasing inequalities. The restarting of the preventive programs against CC in Mexico offers an opportunity to put in place actions to reduce the disparities in the burden of disease between socioeconomic levels.

The benefit of adding the antiangiogenic drug aflibercept to FOLFIRI regime in metastatic colorectal cancer (CRC) patients resistant to or progressive on an oxaliplatin-based therapy has been previously demonstrated. However, the absence of validated biomarkers to predict greater outcomes is a major challenge encountered when using antiangiogenic therapies. In this study we investigated profiles of circulating microRNAs (miRNAs) to build predictive models of response to treatment and survival. Plasma was obtained from 98 metastatic CRC patients enrolled in a clinical phase II trial before receiving FOLFIRI plus aflibercept treatment, and the circulating levels of 754 individual miRNAs were quantified using real-time PCR. A distinct signature of circulating miRNAs differentiated responder from non-responder patients. Remarkably, most of these miRNAs were found to target genes that are involved in angiogenic processes. Accordingly, some of these miRNAs had predictive value and entered in predictive models of response to therapy, progression of disease, and survival of patients treated with FOLFIRI plus aflibercept. Among these miRNAs, circulating levels of hsa-miR-33b-5p efficiently discriminated between responder and non-responder patients and predicted the risk of disease progression. Moreover, the combination of circulating VEGF-A and miR-33b-5p levels improved clinical stratification of metastatic CRC patients who were to receive FOLFIRI plus aflibercept treatment. In conclusion, our study supports circulating miRNAs as valuable biomarkers for predicting better outcomes in metastatic CRC patients treated with FOLFIRI plus aflibercept.

Type 2 diabetes (T2D) is one of the most common diseases and the 8th leading cause of death worldwide. Individuals with T2D are at risk for several health complications that reduce their life expectancy and quality of life. Although several drugs for treating T2D are currently available, many of them have reported side effects ranging from mild to severe. In this work, we present the synthesis in a gram-scale as well as the in silico and in vitro activity of two semisynthetic glycyrrhetinic acid (GA) derivatives (namely FC-114 and FC-122) against Protein Tyrosine Phosphatase 1B (PTP1B) and α-glucosidase enzymes. Furthermore, the in vitro cytotoxicity assay on Human Foreskin fibroblast and the in vivo acute oral toxicity was also conducted. The anti-diabetic activity was determined in streptozotocin-induced diabetic rats after oral administration with FC-114 or FC-122. Results showed that both GA derivatives have potent PTP1B inhibitory activity being FC-122, a dual PTP1B/α-glucosidase inhibitor that could increase insulin sensitivity and reduce intestinal glucose absorption. Molecular docking, molecular dynamics, and enzymatic kinetics studies revealed the inhibition mechanism of FC-122 against α-glucosidase. Both GA derivatives were safe and showed better anti-diabetic activity in vivo than the reference drug acarbose. Moreover, FC-114 improves insulin levels while decreasing LDL and total cholesterol levels without decreasing HDL cholesterol.

Abstract Background HPV self-sampling has been widely supported by the scientific community following a strong body of literature on the subject. Self-sampling is important in cervical cancer screening as it has been shown to improve participation. It is well documented that HPV-testing has proven superior to cytology with regards to sensitivity in detection of CIN and cancer. The value of self-collected samples is reliant on the quality of the molecular testing performed, as well as the patients’ preference in sampling procedure and compliance to follow up on positive test results. Due to the incompatibility of self-samples and cytology, triage of HPV-DNA positives by testing for molecular biomarkers is highly warranted. Methods Our objective was to compare the detection rate of genital Human Papillomavirus (HPV) infection in self- and clinician-collected samples by a 14-type HPV-DNA test and a 7-type mRNA E6/E7 test. Results Five hundred five women were recruited. Each study participant had two sample collection procedures performed upon the same visit, alternating order in execution of the self-collection or the clinician-taken procedure first or second, 1010 samples in total. HPV-DNA prevalence was 22.8% in self-collected versus 19.2% in clinician-collected samples (P = 0.19). Overexpression of mRNA E6/E7 from 7 HPV types was 7.1 and 6.3%, respectively (P = 0.71). The difference between HPV-DNA and HPV-mRNA positivity rates were statistically significant in both self-collected (22.8% versus 7.1%, P

Objective: To evaluate the effect of prolactin (PRL) on the migration of MCF-7 breast cancer cells and the expression of E-cadherin. Methods: We used the wound healing assays to evaluate the migration of MCF-7 cells and the Western blot technique to evaluate the expression of E-cadherin. Results: The results show that PRL produced an increase in the migration of MCF-7 cells without inducing a reduction in the expression of E-cadherin. Conclusions: Prolactin significantly increased the migration of MCF-7 breast cancer cell line without inducing an epithelial-mesenchymal transition (EMT), which could be related to a collective type of migration.

Abstract Introduction The Central Mediterranean Route, passing through Libya, is one of the most dangerous for migrants. Episodes of violence have been documented but have not been accurately quantified. The objective of the study was to estimate the prevalence of episodes of violence suffered in Libya by migrants consulting the Médecins du Monde reception and healthcare centre in Seine-Saint-Denis (Ile-de-France). Methodology A monocentric cross-sectional study was conducted from February to May 2019 including migrants over the age of 18 years who had passed through Libya and arrived in Europe from 2017. The presence of emotional distress was considered as exclusion criterion. The proportion, frequency and factors associated to physical, deprivation and sexual violence in Libya were estimated through a bespoke questionnaire, as well as healthcare access in Libya and psychosocial support needs. Results Ninety eight people were recruited and 72 were interviewed (17 refused to participate and 9 were excluded). 76.4% were men, with a mean age of 31.9 years, 76.4% had low educational level, 66.7% came from Ivory Coast and 59.7% had left their country for security reasons. The median length of stay in Libya was 180 days. The overall proportion of participants having suffered from violence was 96.4% among men and 88.2% among women. The prevalence of physical, deprivation and sexual violence for men and women were 94.2, 81.7 and 18% and 80.0, 86.7 and 53.3%, respectively. Access to healthcare in Libya was 2.8 and 63.9% of participants were oriented to psychosocial support after the interview. Conclusions The vast majority of migrants reported having been victims of violence during their transit through Libya. Women were at particular risk of sexual violence. Access to health care in Libya was almost non-existent. Psychosocial support for this population is urgent.

Methane (CH4) is a greenhouse gas generated during the feed fermentation processes in the rumen. However, numerous studies have been conducted to determine the capacity of plant secondary metabolites to enhance ruminal fermentation and decrease CH4 production, especially those plants rich in tannins. This review conducted a descriptive analysis and meta-analysis of the use of tannin-rich plants in tropical regions to mitigate CH4 production from livestock. The aim of this study was to analyse the effect of tannins supplementation in tropical plants on CH4 production in ruminants using a meta-analytic approach and the effect on microbial population. Sources of heterogeneity were explored using a meta-regression analysis. Final database was integrated by a total of 14 trials. The ‘meta’ package in R statistical software was used to conduct the meta-analyses. The covariates defined a priori in the current meta-regression were inclusion level, species (sheep, beef cattle, dairy cattle, and cross-bred heifers) and plant. Results showed that supplementation with tropical plants with tannin contents have the greatest effects on CH4 mitigation . A negative relationship was observed between the level of inclusion and CH4 emission (−0.09), which means that the effect of CH4 mitigation is increasing as the level of tannin inclusion is higher. Therefore, less CH4 production will be obtained when supplementing tropical plants in the diet with a high dose of tannins.

Flourensia cernua is a bush that grows in the semi-desert regions of Mexico. It has been used in traditional medicine due to its healing properties and currently represents an alternative source of bioactive molecules for different areas of the agri-food and health industries. The objective of this study was to extract and characterize the purified polyphenolic compounds (PPCs) and essential oils (EOs) of F. cernua leaves, determine the total flavonoid content, evaluate the antioxidant activity by three different assays, and determine, for the first time, its inhibitory effect against enzymes involved in the degradation of carbohydrates (α-amylase and α-glucosidase). In addition, the analysis of functional groups (by FTIR-ATR assay) and the identification of the chemical constituents present in both essential oils and phenolic compounds were carried out by GC/MS and UPLC-QToF/MS2, respectively. The results indicate that PPCs and EOs are rich in flavonoid-type compounds. In addition, they showed potential for free-radical scavenging and the inhibition of the lipid oxidation process. The analyzed EOs and PPCs had potential against α-amylase and α-glucosidase enzymes, which are related to high blood sugar levels. FTIR-ATR analysis allowed for the identification of functional groups characteristic of polyphenolic compounds and the chemical constituents of EOs. Finally, compounds such as caryophyllene, caryophyllene oxide, and germacrene-D were identified by GC/MS assay and luteolin 7-O-rutinoside and apigenin-6-C-glucosyl-8-C-arabinoside by UPLC/QToF-MS2. The results indicate that the PPCs and EOs of F. cernua have the potential to be used as antioxidant and enzyme inhibitor agents.

Abstract Background Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. Methods Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. Main objective: to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). Results Forty-seven patients were included in the study. Median age was 81 years (range 63–89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30–60]. Median PFS was 5.6 months (95%CI 2.7–8.4). Median overall survival (OS) was 16 months (95%CI 7.8–24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3–4 adverse events (AEs). The most common grade 3–4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). Conclusions The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. Trial registration This trial was prospectively registered at EudraCT (2013–000236-94). Date of trial registration: April 9th, 2013.

Although the advantages and disadvantages of asymmetrical thiazolidinediones as insulin-sensitizers have been well-studied, the relevance of symmetry and asymmetry for thiazolidinediones and biguanides has scarcely been explored. Regarding symmetrical molecules, only one thiazolidinedione and no biguanides have been evaluated and proposed as an antihyperglycemic agent for treating type 2 diabetes. Since molecular structure defines physicochemical, pharmacological, and toxicological properties, it is important to gain greater insights into poorly investigated patterns. For example, compounds with intrinsic antioxidant properties commonly have low toxicity. Additionally, the molecular symmetry and asymmetry of ligands are each associated with affinity for certain types of receptors. An advantageous response obtained in one therapeutic application may imply a poor or even adverse effect in another. Within the context of general patterns, each compound must be assessed individually. The current review aimed to summarize the available evidence for the advantages and disadvantages of utilizing symmetrical and asymmetrical thiazolidinediones and biguanides as insulin sensitizers in patients with type 2 diabetes. Other applications of these same compounds are also examined as well as the various uses of additional symmetrical molecules. More research is needed to exploit the potential of symmetrical molecules as insulin sensitizers.

In this study, an alternative extraction technique, ultrasound-assisted extraction, was used to extract the polyphenolic fraction from two different residues of the candelilla plant (Euphorbia antisyphilitica). These metabolites were further analyzed to evaluate their bioactivity as antioxidants. In addition, their functional groups were identified by Fourier transform infrared (FTIR) spectroscopy. The antioxidant assays showed statistically significant differences between the phenolic extracts, with citric acid residues (CAR) exhibiting a higher oxidant effect than sulfuric acid residues (SAR). The CAR from San Jerónimo (SJ) cultivar showed decreased IC50 values (179.441 ± 7.92 μL mL−1, DPPH•), and its polyphenolic fraction was able to inhibit lipid oxidation (70.31 ± 2.50%). FTIR analysis subsequently revealed the presence of functional groups related to polyphenolic compounds, such as hydroxy, carbonyl, carbon double bond, and amine groups. In addition, FTIR spectra showed slight differences in phenolic compounds, due to the strong acid treatment involved in the extraction of wax. The present study demonstrated that candelilla by-products from citric acid-wax extraction have a polyphenolic fraction with strong antioxidant activity, which may be useful in food and pharmaceutical products.

Considered a neurodegenerative disease, Alzheimer’s disease (AD) involves a physiopathological process characterized by the presence of the beta-amyloid peptide, hyperphosphorylated Tau protein, and neuroinflammation. Diabetes mellitus (DM) is an endocrine disease characterized by insulin resistance, where decreased production of this hormone causes a constant state of hyperglycemia. Although it is recognized that DM is a risk factor for the development of AD, the compression of the mechanisms involved is not completely understood. The present review evaluates the information acquired from primary and secondary sources, focusing on the alterations in gene expression associated with AD as well as the alterations in gene expression associated with DM, to later highlight the influence that these types of alterations developed in patients with DM can have on both the development and progression of AD. Finally, we point out those alterations that impact the phosphatidyl Inositol 3 Kinase/Akt (PI3K/Akt) pathway, which seems to intervene in the physiopathological process of both diseases, considering that the compression of these gene alterations can help us understand the intricate link between DM and AD.

ObjectivesTo develop and validate a Patient-Centred Quality of Cancer Care Questionnaire in Spanish (PCQCCQ-S) appropriate to the Mexican context.DesignPsychometric validation of a questionnaire.SettingTwo public oncology hospitals in Mexico City.Participants1809 patients with cancer aged ≥18 years.Source of informationCross-sectional survey.MethodsThe validation procedures comprised (1) content validity through a group of experts and patients; (2) item reduction and evaluation of the factor structure, through an exploratory factor analysis based on the polychoric correlation matrix; (3) internal consistency using Cronbach’s alpha; (4) convergent validity between the PCQCCQ-S and supportive care needs scale; (5) correlation analysis between the PCQCCQ-S and quality of life scale by calculating Spearman’s rank-correlation coefficient; and (6) differentiation by ‘known groups’ through the Wilcoxon rank-sum test.ResultsThe PCQCCQ-S has 30 items with the following five factors accounting for 96.5% of the total variance: (1) timely care; (2) clarity of the information; (3) information for treatment decision-making; (4) activities to address biopsychosocial needs; and (5) respectful and coordinated care. Cronbach’s alpha values ranged from 0.73 to 0.90 among the factors. PCQCCQ-S has moderate convergent validity with supportive care needs scale, revealing that higher quality is correlated with lower patient needs. PCQCCQ-S has acceptable ability to differentiate by ‘known groups’, showing that older patients and those with low levels of education perceived lower total quality of care as compared with their counterparts.ConclusionPCQCCQ-S has acceptable psychometric properties and can be used to measure quality of patient-centred cancer care in Mexico and serve as a reference to develop PCQCCQ-S in other Spanish-speaking countries.

Previous research has supported that personality traits can act to a precursor to media preferences. Due to the ongoing association between morality and media preferences in public and political discourse (e.g., blaming immoral behaviours on media preferences), this research sought to expand the knowledge about factors that contribute to media preferences by investigating if moral reasoning styles explain some of the variance that was not already explained by personality traits. A specific form of media preferences were chosen - lyrical preferences in metal music - as claims between metal lyrical themes and behaviour have been ongoing since the 1980s, despite a lack of empirical evidence to support these claims. A lyrical preferences scale was developed, and utilizing this scale, it was found that different types of metal fans exhibit different moral reasoning styles dependent on their metal sub-genre identification. Further, it was found that moral reasoning styles explain a portion of the variance in lyrical preferences that weren't already explained by personality traits. In particular, lyrical preferences were often thematically consistent with moral reasoning content and personality traits, such as that individuals that preferred lyrics about celebrating metal culture and unity had higher levels of the group loyalty moral reasoning domain alongside being higher in extraversion. The implications of moral reasoning styles and personality traits as being precursors to media preferences are discussed.

According to the World Health Organization, every year about 3.4 million adults die of consequences related to overweight or obesity. People with a Body Mass Index above 30 are more likely to express certain diseases, including some types of cancer. In this narrative review, we assess the role of adipose tissue as a modulator of the endocrine system and facilitator of chronic subclinical inflammation. We discuss how obesity can induce a suitable micro environment for the development of tumors, mainly by enhancing the levels of oxidative stress and the concentrations of hormones such as leptin, insulin and prolactin. We conclude that all together, these factors increase the probability of cancer development.

Background. For the last two decades there has been growing interest in governmental and global health stakeholders about the role that performance measurement and management systems can play for the production of high-quality and safely delivered primary care services. Despite recognition and interest, the gaps in evidence in this field of research and practice in low- and middle-income countries remain poorly characterized. This study will develop an evidence gap map in the area of performance management in primary care delivery systems in low- and middle-income countries. Methods. The evidence gap map will follow the methodology developed by 3Ie, the International Initiative for Impact Evaluation, to systematically map evidence and research gaps. The process starts with the development of the scope by creating an evidence-informed framework that helps identify the interventions and outcomes of relevance as well as help define inclusion and exclusion criteria. A search strategy is then developed to guide the systematic search of the literature, covering the following databases: Medline (Ovid), Embase (Ovid), CAB Global Health (Ovid), CINAHL (Ebsco), Cochrane Library, Scopus (Elsevier), and Econlit (Ovid). Sources of grey literature are also searched. Studies that meet the inclusion criteria are systematically coded, extracting data on intervention, outcome, measures, context, geography, equity, and study design. Systematic reviews are also critically appraised using an existing standard checklist. Impact evaluations are not appraised but will be coded according to study design. The process of map-building ends with the creation of an evidence gap map graphic that displays the available evidence according to the intervention and outcome framework of interest. Discussion. Implications arising from the evidence map will be discussed in a separate paper that will summarize findings and make recommendations for the development of a prioritized research agenda.

Background. For the last two decades there has been growing interest in governmental and global health stakeholders about the role that performance measurement and management systems can play for the production of high-quality and safely delivered primary care services. Despite recognition and interest, the gaps in evidence in this field of research and practice in low- and middle-income countries remain poorly characterized. This study will develop an evidence gap map in the area of performance management in primary care delivery systems in low- and middle-income countries. Methods. The evidence gap map will follow the methodology developed by 3Ie, the International Initiative for Impact Evaluation, to systematically map evidence and research gaps. The process starts with the development of the scope by creating an evidence-informed framework that helps identify the interventions and outcomes of relevance as well as help define inclusion and exclusion criteria. A search strategy is then developed to guide the systematic search of the literature, covering the following databases: Medline (Ovid), Embase (Ovid), CAB Global Health (Ovid), CINAHL (Ebsco), Cochrane Library, Scopus (Elsevier), and Econlit (Ovid). Sources of grey literature are also searched. Studies that meet the inclusion criteria are systematically coded, extracting data on intervention, outcome, measures, context, geography, equity, and study design. Systematic reviews are also critically appraised using an existing standard checklist. Impact evaluations are not appraised but will be coded according to study design. The process of map-building ends with the creation of an evidence gap map graphic that displays the available evidence according to the intervention and outcome framework of interest. Discussion. Applications arising from the evidence map will be discussed in a separate paper that will summarize findings and make recommendations for the development of a prioritized research agenda.

Protein tau plays a pivotal role in the pathophysiology of Alzheimer's disease, where its hyperphos-phorylation promotes aggregation and microtubule destabilization. Tau undergoes alternative splicing which generates six isoforms in the human brain, due to inclusion/exclusion of exons 2, 3 and 10. Dysregulation of the splicing process of tau exon 10 is sufficient to cause tauopathy and has shown to be influenced by beta-amyloid peptides, but splicing of other exons is less studied. We studied the effects of beta-amyloid(42) in the alternative splicing of tau exons 2/3 and 6, using untreated and Nerve Growth Factor-induced PC12 cells. Beta-amyloid exposure caused formed cell processes to retract in differentiated cells and altered the expression of exons 2/3 in both undifferentiated and differentiated cells. Expression of exon 6 was repressed in undifferentiated cells only. Our results suggest that beta-amyloid interferes with the splicing process of exons 2/3, favoring their exclusion and thus the expression of immature tau isoforms that are less efficient in stabilizing microtubules and may also be more prone to hyperphosphorylation. The molecular mechanism for this amyloid-tau interaction remains to be determined, but may have potential implications for the understanding of the underlying neuropathological processes in Alzheimer's disease.

Although Alzheimer's disease is a brain disorder, a number of peripheral alterations have been found in these patients; however, little is known about how the key genes involved in the pathophysiology express in peripheral cells such as lymphocytes during normal compared to neuropathological ageing. We analysed the expression of tau, of the amyloid precursor protein, of nicastrin and of the β-site APP cleaving enzyme genes by RT-PCR in lymphocytes from a small group of late-onset Alzheimer's disease patients, from aged patients suffering from neuropsychological conditions different from Alzheimer's and from cognitively healthy subjects divided in four groups by age. We also investigated correlations between gene expression and levels of blood pressure, glucose, total cholesterol and triglycerides as risk factors for Alzheimer's. Results show no tau expression in lymphocytes, a lack of detection of nicastrin expression in Alzheimer's patients and correlations between the medical conditions studied and gene expression in lymphocytes. We believe nicastrin gene expression in lymphocytes should be considered of interest for further analyses in a wider population to investigate whether it might represent a potential biomarker to differentiate Alzheimer's from other neuropsychological disorders.

En este trabajo se presenta la obtención del modelo exacto en tiempo discreto de un robot móvil tipo (2,0), bajo la consideración de la existencia de retardos de transporte en la señal de control, producidos por la propagación de las señales entre los sensores y actuadores del robot y el control remoto. El modelo obtenido es evaluado mediante simulación, comparando su desempeño con un modelo discreto aproximado que incluye también retardos de transporte y con el modelo en tiempo continuo del mismo sistema.

High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent β-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated β-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 β-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 β-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (−25%; p

La Hipótesis de Naturalización de Darwin (HND) plantea que el éxito de naturalización de especies exóticas se ve favorecido cuando el parentesco filogenético entre el colonizador y la comunidad recipiente es distante, debido a que esta situación reduciría la intensidad de la competencia entre especies. Inversamente, especies cercanas filogenéticamente mantendrían alta intensidad de competencia, reduciendo la probabilidad de naturalización. Desde el punto de vista poblacional, el concepto de naturalización es dinámico e involucra dos componentes: el aumento progresivo del tamaño y la distribución espacial de la población invasiva. En el presente estudio, centramos nuestra atención en el componente espacial de la naturalización, evaluando el papel del parentesco filogenético como determinante de la naturalización en la flora exótica presente en Chile continental. Siguiendo la predicción de la HND, sería posible esperar que aquellas especies exóticas emparentadas con la flora nativa debiesen mostrar rangos distribucionales menos extensos que taxa exóticas distantes filogenéticamente. Utilizando el ordenamiento taxonómico APG III como indicador del parentesco filogenético, nuestro análisis mostró que taxa exóticas congenéricas a taxa nativas tienen rangos distribucionales en promedio más extensos que aquellos de parentesco más distante (i.e. especies que pertenecen a familias u órdenes no representados en la flora nativa del país). Estos hallazgos no apoyan la HND ya que las taxa más distantes muestran rangos más reducidos. Los resultados sugieren que el parentesco filogenético podría haber facilitado la naturalización de plantas exóticas en Chile continental, al menos para especies que pertenecen a géneros y familias ya representados en la flora nativa.The Darwin's Naturalization Hypothesis (DNH) states that the successful naturalization of alien species is favored when the phylogenetic relationship between the colonizer and the recipient community is distant. Conversely, related species would compete strongly, hence reducing the probability of naturalization. From a populational perspective, the concept of naturalization involves both the progressive increase in size and spatial distribution of the invasive population. In this study, we focused our attention on the spatial component of naturalization, assessing the role of phylogenetic relatedness as a determinant of its extension. Following the DNH, it is expected that those alien species closely related to the native flora would show narrower distribution ranges than alien taxa less related to native species. Using the APG III taxonomic system as an indicator of phylogenetic relationships in the vascular flora of continental Chile, our analysis showed that alien species with congeneric native counterparts have larger ranges than alien species with a distant relationship (i.e. species belonging to families or orders not represented in the native flora). These results do not support the DNH because the more distant taxa (less related species) show distributional ranges smaller. Results suggest that close relatedness could have facilitated the naturalization of alien plants in continental Chile, at least for species belonging to genus and families represented on the native flora.

It is known that hormones influence significantly the prostate tissue. However, we reported that mating induces an increase in androgen receptors, revealing a neural influence on the gland. These data suggested that somatic afferents (scrotal and genitofemoral nerves) and autonomic efferents (pelvic and hypogastric nerves) could regulate the structure of the prostate. Here we assessed the role of these nerves in maintaining the histology of the gland. Hence, afferent or efferent nerves of male rats were transected. Then, the ventral and dorsolateral regions of the prostate were processed for histology. Results showed that afferent transection affects prostate histology. The alveoli area decreased and increased in the ventral and dorsolateral prostate, respectively. The epithelial cell height increased in both regions. Efferent denervation produced dramatic changes in the prostate gland. The tissue lost its configuration, and the epithelium became scattered and almost vanished. Thus, afferent nerves are responsible for spinal processes pertaining to the trophic control of the prostate, activating its autonomic innervation. Hence, our data imply that innervation seems to be synergic with hormones for the healthy maintenance of the prostate. Thus, it is suggested that some prostate pathologies could be due to the failure of the autonomic neural pathways regulating the gland.Sabe-se que os hormônios influenciam significativamente o tecido prostático. Entretanto, nós demonstramos que o acasalamento induz um aumento nos receptores androgênicos, revelando uma influência neural sobre a glândula. Esses dados sugerem que os aferentes somáticos (nervos escrotal e genito-femural) e os eferentes autonômicos (nervos pélvicos e hipo-gástricos) poderiam regular a estrutura da próstata. Neste trabalho, avaliou-se a função destes nervos na manutenção da histologia da glândula. Dessa forma, os nervos aferentes e eferentes de ratos machos foram seccionados As regiões ventral e dorsolateral da próstata foram processadas para histologia. Os resultados mostraram que a transecção aferente afeta a histologia da próstata. A área alveolar diminuiu e aumentou na próstata dorsal e dorsolateral, respectivamente. A altura da célula epitelial aumentou em ambas as regiões. A desenervação eferente produziu alterações dramáticas na glândula prostática. O tecido perdeu a sua configuração e o epitélio tornou-se difuso e quase desapareceu. Assim, os nervos aferentes são responsáveis por processos espinhais que pertencem ao controle trófico da próstata, ativando sua inervação autonômica. Dessa forma, nossos dados sugerem que a inervação parece ser sinérgica com os hormônios para a manutenção saudável da próstata. Assim, sugere-se que algumas patologias prostáticas poderiam ser ocasionadas devido a falhas nas vias neurais autonômicas que regulam esta glândula.

Neurotensin (NTS)-polyplex is a nanoparticle system for targeted gene delivery that holds great promise for treatment of Parkinson’s disease and various types of cancer. However, the high instability in aqueous suspension of NTS-polyplex nanoparticles is a major limitation for their widespread clinical use. To overcome this obstacle, we developed a clinical formulation and a lyophilization process for NTS-polyplex nanoparticles. The reconstituted samples were compared with fresh preparations by using transmission electron microscopy, dynamic light scattering, electrophoretic mobility, circular dichroism and transfection assays in vitro and in vivo. Our formulation was able to confer lyoprotection and stability to these nanoparticles. In addition, transmission electron microscopy (TEM) and size exclusion-high performance liquid chromatography (SEC-HPLC) using a radioactive tag revealed that the interaction of reconstituted nanoparticles with fetal bovine or human serum did not alter their biophysical features. Furthermore, the formulation and the lyophilization procedure guaranteed functional NTS-polyplex nanoparticles for at least six months of storage at 25 °C and 60% relative humidity. Our results offer a pharmaceutical guide for formulation and long-term storage of NTS-polyplex nanoparticles that could be applied to other polyplexes.

Resumen: En este trabajo se presenta una estrategia de control en tiempo discreto para el seguimiento de trayectorias de un robot móvil tipo (2,0) controlado remotamente. La estrategia de control se desarrolló mediante un enfoque de modos deslizantes, considerando el modelo discreto exacto del vehículo en el cual se incluyen los efectos del retardo de transporte causado por la propagación de las señales sobre una red de comunicación. El esquema de control garantiza el seguimiento de trayectorias predeterminadas obteniéndose convergencia asintótica de los errores de seguimiento. La estrategia propuesta es evaluada mediante una serie de resultados por simulación. Palabras clave: Robot móvil, retardos de transporte, control en tiempo discreto, modos deslizantes