Adherence and impact of an oral nutritional supplement enriched in leucine, EVOO, EPA and DHA, and beta-glucans on the coverage of energy and protein requirements in patients with cancer and malnutrition: Alisenoc study.

OBJECTIVE: The aim of this study was to evaluate the impact of an enhanced ONS (enriched in EPA, DHA, leucine, and beta-glucans) on the dietary intake of cancer patients. METHODS: A randomized, double-blind, parallel, controlled, and multicenter clinical trial was conducted in patients with cancer and malnutrition. The trial compared prescribed dietary advice and two packs per day, for 8 weeks, of a hypercaloric (400 kcal/pack) and hyperproteic ONS (20 g/pack) with fiber and specific ingredients (leucine, EPA and DHA, and beta-glucans) (enhanced-ONS) versus an isocaloric and isoproteic formula (standard-ONS) without specific ingredients. Food intake was assessed with a 3-day dietary survey, and adherence to the supplement with a patient self-completed diary. RESULTS: Thirty-seven patients completed the intervention period. The combined intervention of dietary advice and ONS managed to increase the energy intake of the overall cohort by 792.55 (378.57) kcal/day, protein by 40.72 (19.56) g/day. Increases in energy and nutrient intakes were observed in both groups, both in dietary intake and associated exclusively with the supplement. The group that received the enhanced-ONS ingested a greater volume of product when there was a greater severity of malnutrition; a tumor location in the head, neck, upper digestive area, liver, or pancreas; more advanced stages of the tumor; or the receipt of more than one antineoplastic treatment. CONCLUSION: The use of an enhanced-ONS helps meet the nutritional requirements of cancer patients, especially those who have a more compromised clinical condition, with high adherence, good tolerance, and acceptance.

Bougainvillea glabra Choisy (Nyctinaginacea): review of phytochemistry and antimicrobial potential.

The Bougainvillea glabra or bougainvillea is a climbing plant native from South America belonging to the Nyctaginaceae family. The bougainvillea is recognized worldwide for its horticultural importance, due to the color of its bracts, commonly known as "flowers," made up of bracts, which are the striking parts, and the true flowers, which are white and small. Bougainvillea is widely known in traditional medicine to treat respiratory diseases such as cough, asthma, and bronchitis, gastrointestinal diseases, also for its antibacterial and insecticidal capacity. The antimicrobial potential of the involucre of this plant has not been studied, despite research showing a high phytochemical presence of secondary metabolites such as alkanes, phenols, terpenes, and betalains. This review compiles information about the traditional uses of B. glabra, its botanical description, ecological relevance, phytochemistry, antimicrobial and antibiofilm activity, such as the toxicology of bracts and flowers.

Value contribution of cenobamate for the treatment of Focal-Onset Seizures (FOS) in patients with drug-resistant epilepsy (DRE) in Spain through reflective Multi-Criteria Decision Analysis (MCDA).

INTRODUCTION: Epilepsy is one of the most common neurological conditions worldwide. The main goal of its treatment is to achieve seizure freedom without intolerable adverse effects. However, despite the availability of many anti-seizure medications, including the latest options, called third-generation anti-seizure medications (ASMs), approximately 40% of people with epilepsy present drug-resistant epilepsy (DRE). Cenobamate is the first ASM approved in Spain for the adjunctive treatment of Focal-Onset Seizures (FOS) in adult patients with DRE. In a chronic disease with a portfolio of available ASMs, the decision to introduce a new therapeutic alternative must follow a holistic evaluation of value provided. Reflective Multi-Criteria Decision Analysis (MCDA) methodology allows to determine the value contribution of a treatment in a given indication considering all relevant criteria for healthcare decision-making in a transparent and systematic manner from the perspective of relevant stakeholders. PURPOSE: The aim of this study was to determine the relative value contribution of cenobamate in the treatment of FOS in patients with DRE compared with third-generation ASMs using reflective MCDA-based methodology. METHODS: A systematic literature review (combining biomedical databases and grey literature sources) was performed to populate the Evidence and Value: Impact on DEcisionMaking (EVIDEM) MCDA framework adapted to determine what represents value in the management of FOS in patients with DRE in Spain. The study was conducted in two phases. The first took place in 2021 with a multi-stakeholder group of eight participants. The second phase was conducted in 2022 with a multi-stakeholder group of 32 participants. Participants were trained in MCDA methodology and scored four evidence matrices (cenobamate vs. brivaracetam, vs. perampanel, vs. lacosamide and vs. eslicarbazepine acetate). Results were analyzed and discussed in a group meeting through reflective MCDA discussion methodology. RESULTS: DRE is considered a very severe condition associated with many important unmet needs, mainly with regard to the lack of more effective treatments to achieve the ultimate goal of treatment. Compared to third-generation ASMs, cenobamate is perceived to have a better efficacy profile based on improvements in responder rate and seizure freedom. Regarding safety, it is considered to have a similar profile to alternatives and a positive quality-of-life profile. Cenobamate results in lower direct medical costs (excluding pharmacological) and indirect costs. Overall, cenobamate is regarded as providing a high therapeutic impact and supported by high-quality evidence. CONCLUSIONS: Based on reflective MCDA methodology and stakeholders' experience in clinical management of epilepsy in Spain, cenobamate is perceived as a value-added option for the treatment of patients with DRE when compared with third-generation ASMs.

Real-World Safety and Efficacy Clinical Data of an Improved Allergen-Specific Immunotherapy Product for the Treatment of Bee Venom Allergy.

The aim of this study is to explore the safety and efficacy of bee venom immunotherapy without HSA, in real-life patients. Methods: This is an observational retrospective study developed in seven hospitals in Spain, where patients treated with this immunotherapy were included. They gathered the protocol used to initiate the immunotherapy, adverse reactions, field re-stings, and the patient clinical data (clinical history, biomarkers, and skin prick test). Results: A total of 108 patients were included. In total, 4 protocols were used (5 weeks reaching 200 µg, and 4, 3, and 2 weeks reaching 100 µg). An incidence of systemic adverse reactions for each 100 injections of 1.5, 1.7, 0, and 0.58, respectively, was found. The demographic data showed not to directly affect the appearance of adverse reactions, except for those having a grade 2 systemic reaction with immunotherapy previously had a grade 4 systemic reaction; the IgE to Apis mellifera was 3 times higher in patients with systemic reactions of grade 1 than in the general group, and other specific IgEs were lower in those with systemic reactions. Most of the patients recognized Api m 1 followed by Api m 10. In the sample, 32% experienced spontaneous re-stings, without presenting systemic reactions, after a year of treatment.

Study of ex-ovo embryonic development of Gallus gallus domesticus / Estudio inicial del desarrollo embrionario ex-ovo de Gallus gallus domesticus

SUMMARY: The domestic chicken is a species of bird that has been extensively studied in regard to its biology and as a model organism for science. The reproduction of the species is by the laying of fertilized eggs, which in a period of 21 days will develop a chick inside. Several methods have been described to develop embryos ex-ovo, allowing the observation and manipulation of the organism. This work has the propose to standardize a method that allows the development of the embryos inside the artificial incubation system, which has a low cost and is easy to make. In this work, 100 chicken eggs were used to study the effects of humidity, mineral supplementation, and the preincubation time of the egg on the incubation ex-ovo of the embryos. Embryo development was documented through the different days. Pulverized eggshell was selected as an optimal source to provide calcium, magnesium, phosphorus, and other minerals to the developing embryo. By providing 900-1200 mg of pulverized eggshell, 40 mL of the 0.001 % solution of benzalkonium chloride, and a preincubation time of approximately 56 h, the embryos were able to develop until 19 days, and even though they did not reach hatching, the incubation conditions that allowed the survival and development of embryos until late stages were achieved. Thus, due to the conditions established for calcium, humidity and preincubation time, in the present work, the chicks reached 19 days of development.

El pollo doméstico es una especie de ave que ha sido ampliamente estudiada en cuanto a su biología y como organismo modelo para la ciencia. La reproducción de la especie es por la puesta de huevos fecundados, que en un período de 21 días desarrollarán un polluelo en su interior. Se han descrito varios métodos para desarrollar embriones ex-ovo, permitiendo la observación y manipulación del organismo. Este trabajo tuvo como objetivo estandarizar un método que permita el desarrollo de los embriones dentro del sistema de incubación artificial, el cual tiene un bajo costo y es fácil de realizar. En este trabajo se utilizaron 100 huevos de gallina para estudiar los efectos de la humedad, la suplementación mineral y el tiempo de preincubación del huevo sobre la incubación ex-ovo de los embriones. El desarrollo embrionario se documentó a través de los diferentes días. Se seleccionó la cáscara de huevo pulverizada como una fuente óptima para proporcionar calcio, magnesio, fósforo y otros minerales al embrión en desarrollo. Al suministrar 900-1200 mg de cáscara de huevo pulverizada, 40 mL de la solución de cloruro de benzalconio al 0.001 % y un tiempo de preincubación de aproximadamente 56 h, los embriones lograron desarrollarse hasta los 19 días, y aunque no llegaron a eclosionar, los embriones lograron desarrollarse hasta los 19 días. Se lograron condiciones de incubación que permitieron la supervivencia y desarrollo de los embriones hasta etapas tardías. Así, debido a las condiciones establecidas de calcio, humedad y tiempo de preincubación, en el presente trabajo los pollitos alcanzaron los 19 días de desarrollo.

Cost-effectiveness of transdiagnostic group cognitive behavioural therapy versus group relaxation therapy for emotional disorders in primary care (PsicAP-Costs2): Protocol for a multicentre randomised controlled trial.

Several randomised controlled trials (RCT) have demonstrated the superiority of transdiagnostic group cognitive-behavioural therapy (TD-CBT) to treatment as usual (TAU) for emotional disorders in primary care. To date, however, no RCTs have been conducted to compare TD-CBT to another active intervention in this setting. Our aim is to conduct a single-blind RCT to compare group TD-CBT plus TAU to progressive muscle relaxation (PMR) plus TAU in adults (age 18 to 65 years) with a suspected emotional disorder. We expect that TD-CBT + TAU will be more cost-effective than TAU + PMR, and that these gains will be maintained at the 12-month follow-up. Seven therapy sessions (1.5 hours each) will be offered over a 24-week period. The study will be carried out at four primary care centres in Cantabria, Spain. The study will take a societal perspective. Psychological assessments will be made at three time points: baseline, post-treatment, and at 12-months. The following variables will be evaluated: clinical symptoms (anxiety, depression, and/or somatic); functioning; quality of life (QoL); cognitive-emotional factors (rumination, worry, attentional and interpretative biases, emotion regulation and meta-cognitive beliefs); and satisfaction with treatment. Data on health service use, medications, and sick days will be obtained from electronic medical records. Primary outcome measures will include: incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICURs). Secondary outcome measures will include: clinical symptoms, QoL, functioning, and treatment satisfaction. Bootstrap sampling will be used to assess uncertainty of the results. Secondary moderation and mediation analyses will be conducted. Two questionnaires will be administered at sessions 1, 4, and 7 to assess therapeutic alliance and group satisfaction. If this trial is successful, widespread application of this cost-effective treatment could greatly improve access to psychological treatment for emotional disorders in the context of increasing demand for mental healthcare in primary care. Trial registration: ClinicalTrials.gov: Cost-effectiveness of a Transdiagnostic Psychological Treatment for Emotional Disorders in Primary Care (PsicAP). NCT05314920.

COVID-19's impact on care practice for alpha-1-antitrypsin deficiency patients.

BACKGROUND: Patients with alpha-1 antitrypsin deficiency (AATD), commonly categorized as a rare disease, have been affected by the changes in healthcare management brought about by COVID-19. This study's aim was to identify the changes that have taken place in AATD patient care as a result of the COVID-19 pandemic in Spain and to propose experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. METHODS: A qualitative descriptive case study with a holistic single-case design was conducted, using focus groups with experts in AATD clinical management, including 15 health professionals with ties to the Spanish health system (12 pneumologists and 2 hospital pharmacists from 11 different hospitals in Spain) and 1 patient representative. RESULTS: COVID-19 has had a major impact on numerous aspects of AATD clinical patient management in Spain, including diagnostic, treatment, and follow-up phases. The experts concluded that there is a need to strengthen coordination between Primary Care and Hospital Care and improve the coordination processes across all the organizations and actors involved in the healthcare system. Regarding telemedicine and telecare, experts have concluded that it is necessary to promote this methodology and to develop protocols and training programs. Experts have recommended developing personalized and precision medicine, and patient participation in decision-making, promoting self-care and patient autonomy to optimize their healthcare and improve their quality of life. The possibility of monitoring and treating AATD patients from home has also been proposed by experts. Another result of the study was the recommendation of the need to ensure that plasma donations are made on a regular basis by a sufficient number of healthy individuals. CONCLUSION: The study advances knowledge by highlighting the challenges faced by health professionals and changes in AATD patient management in the context of the COVID-19 pandemic. It also proposes experts' recommendations aimed at ensuring humanized and quality care for people with AATD in the post-pandemic situation. This work could serve as a reference study for physicians on their daily clinical practice with AATD patients and may also provide guidance on the changes to be put in place for the post-pandemic situation.

Camel (Camelus spp.) Urine Bioactivity and Metabolome: A Systematic Review of Knowledge Gaps, Advances, and Directions for Future Research.

Up to the present day, studies on the therapeutic properties of camel (Camelus spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence across studies regarding the methods for sample storage, pre-processing, and extract derivatization for metabolomic analysis. Additionally, medium osmolarity is not experimentally adjusted prior to bioactivity assays. In this scenario, the methodological standardization and interdisciplinary approach of such processes will strengthen the interpretation, repeatability, and replicability of the empirical results on the compounds with bioactive properties present in camel urine. Furthermore, sample enlargement would also permit the evaluation of camel urine's intra- and interindividual variability in terms of chemical composition, bioactive effects, and efficacy, while it may also permit researchers to discriminate potential animal-intrinsic and extrinsic conditioning factors. Altogether, the results would help to evaluate the role of camel urine as a natural source for the identification and extraction of specific novel bioactive substances that may deserve isolated chemical and pharmacognostic investigations through preclinical tests to determine their biological activity and the suitability of their safety profile for their potential inclusion in therapeutic formulas for improving human and animal health.

The mobility of thorium, uranium and rare earth elements from Mid Ordovician black shales to acid waters and its removal by goethite and schwertmannite.

Previous studies have addressed the occurrence of Acid Rock Drainage (ARD) affecting La Silva stream due to the generation of large dumps of Middle Ordovician black shales during the construction of a highway close to El Bierzo (León, Spain). This ARD was characterized by sulphated acid waters with high concentration of heavy metals and anomalies in dissolved thorium (Th) and uranium (U). In the present study, we analyse in depth black shales and water, streambed sediments and precipitates of La Silva stream and its tributaries using different petrographic, mineralogical and geochemical approaches. Black shales, with average Th and U contents of 20 and 3 µg/g respectively contain disseminated detritic micro-grains of high weathering-resistant minerals, such as monazite and xenotime, that present smaller amounts of yttrium and rare earth elements (REY) and other elements as Ca, U, Th, Si and F. Results of the affected waters by ARD show an enrichment in dissolved Th, U and REY of several orders of magnitude with respect to natural waters. Sampled precipitates were mainly schwertmannite (Fe8O8(OH)8-2x (SO4)xO16•nH2O) and goethite (α-Fe3+O(OH)) that showed an enrichment of Th (up to 798 µg/g) and REY, due to the presence of dissolved anionic species (e.g. [Formula: see text] , [Formula: see text] ) that enables their adsorption. Furthermore, these black shales show a clear enrichment in REE (Rare Earth Elements) with respect to NASC (North American Shales Composite) normalized REE patterns. Likewise, normalized REE patterns of stream waters and precipitates clearly show convex curvatures in middle-REE (MREE) with respect to light- and something less than heavy-REE, indicating the trend towards MREE enrichment. These findings are essential to evaluate the impact of ARD of Mid Ordovician shales in the surrounding environment, and to start considering these site as potential source of REE and critical raw materials, activating a Circular Economy.

Cost-effectiveness and cost-utility evaluation of individual vs. group transdiagnostic psychological treatment for emotional disorders in primary care (PsicAP-Costs): a multicentre randomized controlled trial protocol.

BACKGROUND: Emotional disorders are common, and they have become more prevalent since the COVID-19 pandemic. Due to a high attendance burden at the specialized level, most emotional disorders in Spain are treated in primary care, where they are usually misdiagnosed and treated using psychotropic drugs. This contributes to perpetuate their illness and increase health care costs. Following the IAPT programme and the transdiagnostic approach, the PsicAP project developed a brief group transdiagnostic cognitive-behavioural therapy (tCBT) as a cost-effective alternative. However, it is not suitable for everyone; in some cases, one-on-one sessions may be more effective. The objective of the present study is to compare, in cost-benefit terms, group and individual tCBT with the treatment usually administered in Spanish primary care (TAU). METHODS: A randomized, controlled, multicentre, and single-blinded trial will be performed. Adults with mild to moderate emotional disorders will be recruited and placed in one of three arms: group tCBT, individual tCBT, or TAU. Medical data and outcomes regarding emotional symptoms, disability, quality of life, and emotion regulation biases will be collected at baseline, immediately after treatment, and 6 and 12 months later. The data will be used to calculate incremental cost-effectiveness and cost-utility ratios. DISCUSSION: This trial aims to contribute to clinical practice research. The involvement of psychologists in primary care and the implementation of a stepped-care model for mental disorders are recommended. Group therapy and a transdiagnostic approach may help optimize health system resources and unblock waiting lists so that people can spend less time experiencing mental health problems. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04847310; Protocols.io: bx2npqde. (April 19, 2021).

Ketogenic Diet Decreases Alcohol Intake in Adult Male Mice.

The classic ketogenic diet is a diet high in fat, low in carbohydrates, and well-adjusted proteins. The reduction in glucose levels induces changes in the body's metabolism, since the main energy source happens to be ketone bodies. Recent studies have suggested that nutritional interventions may modulate drug addiction. The present work aimed to study the potential effects of a classic ketogenic diet in modulating alcohol consumption and its rewarding effects. Two groups of adult male mice were employed in this study, one exposed to a standard diet (SD, n = 15) and the other to a ketogenic diet (KD, n = 16). When a ketotic state was stable for 7 days, animals were exposed to the oral self-administration paradigm to evaluate the reinforcing and motivating effects of ethanol. Rt-PCR analyses were performed evaluating dopamine, adenosine, CB1, and Oprm gene expression. Our results showed that animals in a ketotic state displayed an overall decrease in ethanol consumption without changes in their motivation to drink. Gene expression analyses point to several alterations in the dopamine, adenosine, and cannabinoid systems. Our results suggest that nutritional interventions may be a useful complementary tool in treating alcohol-use disorders.

Activation of the Keap1-Nrf2 pathway by specioside and the n-butanol extract from the inner bark of Tabebuia rosea (Bertol) DC.

Background: A large number of chemical compounds exert their antioxidant effects by activation of key transcriptional regulatory mechanisms, such as the transcription factor Nrf2. The aim of this study was to evaluate the activation of the Keap1-Nrf2 pathway by both the n-butanol extract obtained from the inner bark of Tabebuia rosea (Bertol) DC and specioside isolated from this extract. Methods: The antioxidant activity of the extract and specioside isolated from the inner bark of T. rosea were evaluated using the oxygen radical absorbance capacity (ORAC) and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (DPPH) techniques, whereas their effects on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The effects of the compound and the extract on activating the Keap1-Nrf2 pathway were evaluated using a Nrf2 Transcription Factor Assay kit. Induction of the Nrf2-mediated antioxidant response genes HMOX-1 and NQO1 was evaluated by real-time PCR. The protective effects against H 2O 2-induced oxidative stress in HepG2 cells was determined as the percent protection using the MTT method. Results: Both the n-butanol extract and specioside exhibited activity at low concentrations without affecting cellular viability, since the cell viability was greater than 80% after 24 hours of exposure at each tested concentration. In addition, Nrf2 dissociated from Keap1 after treatment with the n-butanol extract at a concentration of 0.25 µg/mL after 4 hours of exposure. An increase in the Nrf2 level in the cytoplasm after 4 hours of exposure to 2 µM specioside was observed. Nrf2 levels stabilized in the nucleus 12 hours after stimulation with both specioside and the extract. After 6 hours of stimulation, both the extract and specioside induced the expression of HMOX-1 and NQO1. Conclusion: The n-butanol extract from the inner bark of T. rosea and specioside produced protective effects against H 2O 2-induced oxidative stress in HepG2 cells.

Screening of drugs and homeopathic products from Atropa belladonna seed extracts: Tropane alkaloids determination and untargeted analysis.

Homeopathic products are still a controversial issue in modern medicine, understood as complementary or alternative medicine (CAM). In this particular case, homeopathic products prepared from Atropa belladonna extracts may present specific problems due to the effects derived from its components. This article applies a simple, rapid, reliable method to the analysis of different homeopathic products obtained from Atropa belladonna; drugs containing high concentration of plant extracts; and Atropa belladonna seeds. The method was based on a simple solid-phase preconcentration method followed by ultra-high pressure liquid chromatography (UHPLC) coupled to high resolution mass spectrometry using Exactive-Orbitrap as an analyser. An in-house database was set and atropine and scopolamine were the compounds detected at highest concentrations in homeopathic products from Atropa belladonna extracts (4.57 and 2.56 µg/kg, respectively), in Belladonna ointment (4007 and 1139 µg/kg, respectively) and Belladonna seeds (338 and 32.1 mg/kg, respectively). Other tropane alkaloids such as tropine, apoatropine, aposcopolamine, tropinone, homatropine, and anisodamine were detected at lower concentrations (0.04-1.36 µg/kg). When untargeted analysis was performed, other tropane alkaloids were identified in the tested samples, such as ecgonine (0.003 µg/kg), benzoylecgonine (0.56 µg/kg), calystegines A (19.6 µg/kg), B (33.1 µg/kg), and C (1.01 µg/kg). Finally other compounds present in the homeopathic products, such as sugars (fructose, glucose, and lactose) or amino acids (valine, ornithine, leucine, and phenylalanine), were identified.

Genetic parameter estimation and implementation of the genetic evaluation for gaits in a breeding program for assisted-therapy in donkeys.

Genetic analyses in donkeys are likely to face compromises in terms of sample size and population structure. This study aims at implementing a suitable model to estimate breeding values and genetic parameters for gaits in Andalusian donkeys. Empirical observation revealed that ambling donkeys (showing a slightly uneven, non-isochronous 1-2, 3-4 lateral sequence gait) did not walk (i.e. presented an isochronous, even 1-2-3-4 sequence gait) and vice versa. However, the two donkey groups could trot, equally. In this study, 2700 gait records were registered from 300 donkeys. The sample included 1350 gait records from 169 ambling/trotting donkeys and 1350 gait records from 131 walking/trotting donkeys. Fixed effects included year, season, sex, farm/owner, husbandry system, weather, ground type and appraisers. Weight and age were included as covariates. MTDFREML software was used to estimate (co)variance components, genetic parameters and predict breeding values and their accuracies in both sets, separately. Gaits' heritability ± SE estimates were 0.56 ± 0.155, 0.53 ± 0.317 and 0.67 ± 0.166 for amble, walk and trot, respectively. Genetic correlations were 0.31 ± 0.216, 0.42 ± 0.115 and 0.28 ± 0.178, for amble and walk, amble and trot and walk and trot, respectively. Not all gaits are suitable to treat every human sensomotor condition. We developed a locomotion selection index, assessing the relative loss/gain in index accuracy when each gait modality was excluded to develop different gait specific therapeutic lines to genetically select the best performing donkeys from each gait modality. Our results suggest that gait genetic lines could be developed and may be potential selection criteria to consider in assisted-therapy donkey breeding programs.

La importancia de interrogar el trabajo del paciente: a propósito de un caso de leptospirosis / Report of a case of leptospirosis: the importance of asking the patient about workplace factors

No disponible

Nrf2-Mediated Antioxidant Activity of the inner bark extracts obtained from Tabebuia rosea (Bertol) DC and Tabebuia chrysantha (JACQ) G. Nicholson.

Background: Several ethnobotanical and ethnopharmacological studies have shown the therapeutic potential of plants from the genus Tabebuia, which have long been used in traditional medicine in rural areas of South America, for the treatment of several human diseases. This study aimed to evaluate the Nrf2-mediated antioxidant activity of the inner bark extracts obtained from Tabebuia rosea and Tabebuia chrysantha. Methods: The antioxidant activity of extracts obtained from the inner bark of T. rosea and T. chrysantha was evaluated using the Oxygen radical absorbance capacity (ORAC) technique. The effect of extracts on the viability of HepG2 cells was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) method. The translocation of Nrf2 to the nucleus after exposure of HepG2 cells to the extracts and controls (α-lipoic acid, curcumin and hydrogen peroxide) was evaluated using the Nrf2 transcription factor kit. Induction of the Nrf2-mediated antioxidant response gene ( NQO1) was evaluated by real-time PCR. Results: The ethyl acetate extract obtained from both species displayed the highest ORAC activity (12,523 and 6,325 µmoles Eq Trolox/g extract). In addition, the extracts had the ability to activate and to translocate Nrf2 to the nucleus, as well as to induce the expression of NQO1. Conclusion: These results indicate that the ethyl acetate extracts obtained from the inner bark of T. chrysantha and T. rosea have an important antioxidant effect mediated by Nrf2 activation, and could be used as a new source of natural antioxidants.

The effects of a high-protein, high-calorie, fiber- and fructo-oligosaccharide-enriched enteral formula on nutritional status, bowel habits and tolerance: Safety and Effectiveness of Enteral Nutrition in elderly Spanish patients (SENS Study) / Fórmula enteral hiperproteica e hipercalórica, enriquecida en fibra y en fructooligosacáridos: efecto sobre el estado nutricional, hábitos gastrointestinales y tolerancia en pacientes ancianos españoles (Estudio SENS)

Background: Enteral nutrition (EN) is an effective nutritional intervention for patients at risk of malnutrition or malnourished. However, complications such as gastrointestinal intolerance, hyperglycemia or refeeding syndrome can be triggered by EN. Aim: To investigate the effects of a tube feeding formula (TFF) on patients' nutritional status, biochemical status, bowel habits and safety. Methodology: Observational, prospective and multicenter study. Patients ≥ 18 years, undernourished or at nutritional risk, who were prescribed a high-calorie, high-protein, fiber-fortified TFF were included. Patients were evaluated over a period of eight weeks (baseline [V1], four weeks [V2] and eight weeks [V3]). Results: A statistically significant increase in weight (1.5 kg), body mass index (0.6 kg/m2) and nutritional intake (59.7 kcal/day) was observed between V1 and V2. Between V1 and V3, there was a statistically significant decrease in the percentage of individuals with abnormal biochemical markers for glucose, potassium, total protein and albumin. The number of patients’ bowel movements remained stable throughout the study with a mean of 1.1 daily bowel movements. Conclusion: The TFF was safe and well tolerated, improving patients’ nutritional status without altering patients' bowel habits (AU)

Introducción: la nutrición enteral es una intervención efectiva para pacientes desnutridos o en riesgo de sufrir desnutrición. Sin embargo, puede desencadenar complicaciones como intolerancia gastrointestinal, hiperglicemia o síndrome de realimentación. Objetivo: investigar los efectos de una fórmula de nutrición enteral por sonda en el estado nutricional y bioquímico, hábitos gastrointestinales y seguridad de los pacientes. Metodología: estudio observacional, prospectivo y multicéntrico. Se incluyeron pacientes ≥ 18 años, desnutridos o en riesgo de desnutrición, tributarios de recibir una fórmula de nutrición enteral hipercalórica, hiperproteica, y rica en fibra y fructooligosacáridos. Los pacientes fueron evaluados durante 8 semanas en 3 visitas (V1, inicial; V2, 4 semanas; V3, 8 semanas). Resultados: entre V1 y V2 se observó un incremento estadísticamente significativo en peso (1,5 kg), índice de masa corporal (0,6 kg/m2) e ingesta calórica (59,7 kcal/día). Entre V1 y V3, existió un descenso en el porcentaje de pacientes con valores anormales de glucosa, potasio, proteína total y albúmina. Los hábitos intestinales se mantuvieron estables durante el estudio (1,1 deposiciones diarias de media). Conclusión: la fórmula fue segura, tolerada, y mejoró el estado nutricional del paciente sin alterar los hábitos intestinales (AU)

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance.

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum (ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPKα1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.

Synthesis and in vitro antiproliferative evaluation of PEGylated triterpene acids.

A set of PEGylated derivatives of oleanolic and maslinic acids has been semi-synthesised, attaching ethylene glycol, diethylene glycol, triethylene glycol or tetraethylene glycol to the C-28 carboxyl group of these natural triterpenes and some derivatives. Another set of PEGylated derivatives has been semi-synthesised by connecting the same four ethylene glycols to the hydroxyl groups of the A ring of these triterpenic acids, through a carbonate linker, by reaction with trichloromethyl chloroformate. The aqueous solubility of some of these PEGylated derivatives has been compared with that of maslinic acid. The cytotoxic effects of 28 triterpenic PEGylated derivatives in three cancer-cell lines (B16-F10, HT29, and Hep G2) have been assayed. The best results have been achieved with the HT29 cell line, and specifically with the oleanolic acid derivatives having ethylene glycol or tetraethylene glycol attached to the C-28 carboxyl group, which are approximately 27-fold more effective than their natural precursor. Eight PEGylated derivatives have been selected to compare the cytotoxicity results in the HT29 cancer-cell line with those of a non-tumour cell line of the same tissue (IEC-18), four of which were less cytotoxic in the non-tumour cell line. These compounds showed apoptotic effects on treated cells, with percentages of total apoptosis between 20% and 53%, relative to control, at 72h and IC50 concentration, and between 29% to 62%, relative to control, for the same time and IC80 concentration. We have also found that with the treatment of these compounds in HT29 cancer cells, cell-cycle arrest occurred in the G0/G1 phase. Finally, we have also studied changes in mitochondrial membrane potential during apoptosis of HT29 cancer cells, and the results suggest an activation of the extrinsic apoptotic pathway for these compounds.

Auxotrophic Actinobacillus pleurpneumoniae grows in multispecies biofilms without the need for nicotinamide-adenine dinucleotide (NAD) supplementation.

BACKGROUND: Actinobacillus pleuropneumoniae is the etiologic agent of porcine contagious pleuropneumonia, which causes important worldwide economic losses in the swine industry. Several respiratory tract infections are associated with biofilm formation, and A. pleuropneumoniae has the ability to form biofilms in vitro. Biofilms are structured communities of bacterial cells enclosed in a self-produced polymer matrix that are attached to an abiotic or biotic surface. Virtually all bacteria can grow as a biofilm, and multi-species biofilms are the most common form of microbial growth in nature. The goal of this study was to determine the ability of A. pleuropneumoniae to form multi-species biofilms with other bacteria frequently founded in pig farms, in the absence of pyridine compounds (nicotinamide mononucleotide [NMN], nicotinamide riboside [NR] or nicotinamide adenine dinucleotide [NAD]) that are essential for the growth of A. pleuropneumoniae. RESULTS: For the biofilm assay, strain 719, a field isolate of A. pleuropneumoniae serovar 1, was mixed with swine isolates of Streptococcus suis, Bordetella bronchiseptica, Pasteurella multocida, Staphylococcus aureus or Escherichia coli, and deposited in 96-well microtiter plates. Based on the CFU results, A. pleuropneumoniae was able to grow with every species tested in the absence of pyridine compounds in the culture media. Interestingly, A. pleuropneumoniae was also able to form strong biofilms when mixed with S. suis, B. bronchiseptica or S. aureus. In the presence of E. coli, A. pleuropneumoniae only formed a weak biofilm. The live and dead populations, and the matrix composition of multi-species biofilms were also characterized using fluorescent markers and enzyme treatments. The results indicated that poly-N-acetyl-glucosamine remains the primary component responsible for the biofilm structure. CONCLUSIONS: In conclusion, A. pleuropneumoniae apparently is able to satisfy the requirement of pyridine compounds through of other swine pathogens by cross-feeding, which enables A. pleuropneumoniae to grow and form multi-species biofilms.