Search

Abstract Epilepsy, a widespread neural ailment considered by prolonged neuronal depolarization and repetitive discharge, has been linked to extreme stimulus of N-methyl-D-aspartate receptors (NMDARs). Despite the availability of approved anti-seizure medications (ASMs) in many developed nations, approximately 30% of epilepsy patients continue to experience drug-resistant seizures. Thus, a growing interest in discovering natural compounds as potential sources for new medications is growing. Sinapinic acid, a natural derivative of cinnamic acid found in food sources, is known for its neuroprotective properties. This study investigated how sinapinic acid interacts with NMDA receptors and its potential role in providing anticonvulsant effects. Male mice were randomly allocated into nine groups: a control group receiving normal saline (1 ml/kg), groups treated with sinapinic acid at doses of 1, 3, and 10 mg/kg, a group treated with diazepam at 10 mg/kg, a group treated with an NMDA agonist at 75 mg/kg, a group treated with an NMDA antagonist at 0.5 mg/kg, a group receiving the ineffective dose of sinapinic acid (1 mg/kg) along with the NMDA antagonist, and a group receiving the effective dose of sinapinic acid (10 mg/kg) along with the NMDA agonist. Sinapinic acid and other treatments were administered intraperitoneally 30 min prior to inducing seizures with PTZ injection. Seizure onset time was recorded following PTZ injection. Blood and brain samples were collected after anesthesia to determine serum and brain nitrite levels. Real-time PCR assessed NMDAR gene expression in the prefrontal cortex (PFC). Data were analyzed using Prism software. The time seizures began was notably extended in groups treated with sinapinic acid at doses of 3 and 10 mg/kg compared to those treated with saline (P

Abstract Background Variations in body weight (BW) remain a significant challenge within broiler flocks, despite uniform management practices. Chicken growth traits are influenced by gut microbiota, which are in turn shaped by early-life events like different hatching environments and timing of first feeding. Chicks hatched in hatcheries (HH) experience prolonged feed deprivation, which could adversely impact early microbiota colonization. Conversely, hatching on-farm (HOF) allows early feeding, potentially fostering a more favorable gut environment for beneficial microbial establishment. This study investigates whether BW differences among broilers are linked to the disparities in gut microbiota characteristics and whether hatching systems (HS) impact the initial microbial colonization of broilers differing in BW, which in turn affects their growth patterns. Male Ross-308 chicks, either hatched in a hatchery or on-farm, were categorized into low (LBW) and high (HBW) BW groups on day 7, making a two-factorial design (HS × BW). Production parameters were recorded periodically. On days 7, 14, and 38, cecal volatile fatty acid (VFA) and microbiota composition and function (using 16 S rRNA gene sequencing and PICRUSt2) were examined. Results HOF chicks had higher day 1 BW, but HH chicks caught up within first week, with no further HS-related performance differences. The HBW chicks remained heavier attributed to higher feed intake rather than improved feed efficiency. HBW group had higher acetate concentration on day 14, while LBW group exhibited higher isocaproate on day 7 and isobutyrate on days 14 and 38. Microbiota analyses revealed diversity and composition were primarily influenced by BW than by HS, with HS having minimal impact on BW-related microbiota. The HBW group on various growth stages was enriched in VFA-producing bacteria like unclassified Lachnospiraceae, Alistipes and Faecalibacterium, while the LBW group had higher abundances of Lactobacillus, Akkermansia and Escherichia-Shigella. HBW microbiota presented higher predicted functional potential compared to the LBW group, with early colonizers exhibiting greater metabolic activity than late colonizers. Conclusions Despite differences in hatching conditions, the effects of HS on broiler performance were transient, and barely impacting BW-related microbiota. BW variations among broilers are likely linked to differences in feed intake, VFA profiles, and distinct microbiota compositions and functions.

Abstract Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p 40,000 transplants, providing insights for evaluating emerging DLBCL therapies.

Abstract Glutamatergic neurotransmission and oxidative stress are involved in the pathophysiology of seizures. Some anticonvulsants exert their effects through modulation of these pathways. Trigonelline (TRG) has been shown to possess various pharmacological effects like neuroprotection. Therefore, this study was performed to determine TRG’s anticonvulsant effects, focusing on its potential effects on N-methyl-D-aspartate (NMDA) receptors, a type of glutamate receptor, and oxidative stress state in the prefrontal cortex (PFC) in PTZ-induced seizure in mice. Seventy-two male mice were randomly divided into nine groups. The groups included mice that received normal saline, TRG at doses of 10, 50, and 100 mg/kg, diazepam, NMDA (an agonist), ketamine (an antagonist), the effective dose of TRG with NMDA, as well as sub-effective dose of TRG with ketamine, respectively. All agents were administrated intraperitoneally 60 min before induction of seizures by PTZ. Latency to seizure, total antioxidant capacity (TAC), and malondialdehyde (MDA) levels in serum and PFC were measured. Furthermore, the gene expression of NR2A and NR2B, subunits of NMDA receptors, was measured in the PFC. TRG administration increased the latency to seizure onset and enhanced TAC while reducing MDA levels in both the PFC and serum. TRG also decreased the gene expression of NR2B in the PFC. Unexpectedly, the findings revealed that the concurrent administration of ketamine amplified, whereas NMDA mitigated, the impact of TRG on latency to seizure. Furthermore, NMDA diminished the positive effects of TRG on antioxidant capacity and oxidative stress, while ketamine amplified these beneficial effects, indicating a complex interaction between TRG and NMDA receptor modulation. In the gene expression of NMDA receptors, results showed that ketamine significantly decreased the gene expression of NR2B when co-administrated with a sub-effective dose of TRG. It was found that, at least partially, the anticonvulsant effect of TRG in PTZ-induced seizures in male mice was mediated by the attenuation of glutamatergic neurotransmission as well as the reduction of oxidative stress.

ABSTRACT: Variation in body weight (BW) within broiler flocks is a significant challenge in poultry production. Investigating differences in gut-related parameters between low (LBW) and high BW (HBW) chicks may provide insights into the underlying causes of BW heterogeneity. 908 day-old male broiler chicks were reared until d 7 and then ranked into LBW and HBW groups. Thereafter, performance parameters were compared between BW groups periodically. On d 7, 14, and 38, visceral organ characteristics, intestinal permeability, and duodenal and ileal histomorphology were examined. Expression profiles were analyzed for 79 ileal genes related to gut barrier function, immune function, nutrient transport, gut hormones, nutrient receptors, metabolism, and oxidation using high-throughput qPCR. Student's t-tests were performed to compare measurements. Multivariate statistics, including partial least square regression (PLSR) analysis, were applied to identify combinations of key genes discriminating BW groups, offering predictive capability for phenotypic variations. The HBW group remained heavier at each timepoint, which could be explained by higher feed intake. The HBW group had shorter relative small intestine length but higher villus height and villi height/crypt depth ratios. The LBW group demonstrated increased intestinal permeability on d 38. The LBW group showed upregulation of immune response genes including TNF-α on d 7 and CYP450 on d 38, while the HBW group showed higher AHSA1 and HSPA4 expressions on d 7. The LBW group had upregulation of the metabolism genes mTOR and EIF4EBP1 on d 7 and the satiety-induced hormone cholecystokinin on d 14, while the HBW group tended to increase expression of the hunger hormone ghrelin on d 38. Genes related to gut barrier function, nutrient transport, and oxidation categories were consistently upregulated in the HBW group. PLSR models revealed 4, 12, and 11 sets of key genes highly predictive of BW phenotypes on d 7, 14, and 38, respectively. These findings suggest that growth rates are linked to the intestinal size, structure, and function of broiler chickens, offering insights into the underlying mechanisms regulating BW.

La evaluación del aprendizaje de los estudiantes es un tema de investigación relevante de la didáctica de la matemática. Evaluar en matemática requiere mucho más que la resolución de un ejercicio. Se trata de evaluar todo el proceso. En este sentido, el diseño de evaluaciones no es trivial ni inmediato. Requiere formación, objetivos claros y propuestas relevantes. En este trabajo se analizan las evaluaciones propuestas por tres futuros profesores de matemática y por tres chatbots basados en modelos de Inteligencia Artificial (IA) generativa. Se comparan los tipos de evaluaciones propuestas sobre nociones de estadística (población y muestra) y se determina la funcionalidad de los chatbots como posibles asistentes para la generación de diferentes tipos de evaluaciones. Se concluye que los chatbots pueden resultar en asistentes valiosos a la hora de crear evaluaciones, ya que ofrecen diferentes tipos de evaluaciones, tanto tradicionales, como puede ser una prueba escrita, como no tradicionales, como un proyecto de investigación.

Abstract Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11− MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

Abstract Metabolic syndrome (MetS) is a common disorder involving a cluster of metabolic abnormalities, such as abdominal obesity, hypertension, dyslipidemia, insulin resistance, and atherogenic profile. MetS is characterized by an increase in oxidative stress and a chronic proinflammatory state, which are directly related to the development and progression of this pathology. It has been seen how a healthy lifestyle and good dietary practices are key to improving the different metabolic parameters and, therefore, play a fundamental role in reducing the risk of developing diabetes. The present review focuses on the research evidence related to the therapeutic properties of Lycium barbarum L. in MetS gathered in the last years. Several preclinical studies suggest that L. barbarum extracts are a good dietary supplement for the prevention of cardiovascular diseases in people with MetS. This compound has been used for years in traditional Chinese medicine for the treatment of atrophic gastritis, problems related to the lungs, kidneys, and liver, and as a supplement for eye health. In addition, different in vitro and in vivo studies have been carried out that support the properties attributed to metabolites derived from L. barbarum, such as polysaccharides that have been shown diverse biological activities. In conclusion, L. barbarum extracts have multiple benefits to increase general well‐being and immune function. However, there are a limited number of studies related to effect of L. barbarum in MetS, but they demonstrated effectiveness in the treatment of obesity, diabetes mellitus type 2, and prevention of diabetes mellitus type 2 complication.

Not available.

BackgroundPatients with hematological malignancies receiving hematopoietic cell transplantation (HCT) or chimeric antigen receptor (CAR) T-cell therapy are at risk of developing serious clinical complications after discharge. ObjectiveThe aim of the TEL-HEMATO study was to improve our telehealth platform for the follow-up of patients undergoing HCT or CAR T-cell therapy during the first 3 months after discharge with the addition of wearable devices. MethodsEleven patients who received autologous (n=2) or allogeneic (n=5) HCT or CAR T-cell therapy (n=4) for hematological malignancies were screened from November 2022 to July 2023. Two patients discontinued the study after enrollment. The telehealth platform consisted of the daily collection of vital signs, physical symptoms, and quality of life assessment up to 3 months after hospital discharge. Each patient received a clinically validated smartwatch (ScanWatch) and a digital thermometer, and a dedicated smartphone app was used to collect these data. Daily revision of the data was performed through a web-based platform by a hematologist or a nurse specialized in HCT and CAR T-cell therapy. ResultsVital signs measured through ScanWatch were successfully collected with medium/high adherence: heart rate was recorded in 8/9 (89%) patients, oxygen saturation and daily steps were recorded in 9/9 (100%) patients, and sleeping hours were recorded in 7/9 (78%) patients. However, temperature recorded manually by the patients was associated with lower compliance, which was recorded in 5/9 (55%) patients. Overall, 5/9 (55%) patients reported clinical symptoms in the app. Quality of life assessment was completed by 8/9 (89%) patients at study enrollment, which decreased to 3/9 (33%) at the end of the third month. Usability was considered acceptable through ratings provided on the System Usability Scale. However, technological issues were reported by the patients. ConclusionsWhile the addition of wearable devices to a telehealth clinical platform could have potentially synergic benefits for HCT and CAR T-cell therapy patient monitoring, noncomplete automation of the platform and the absence of a dedicated telemedicine team still represent major limitations to be overcome. This is especially true in our real-life setting where the target population generally comprises patients of older age with a low digital education level.

Objectives: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19. Methods: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs. Results: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92). Conclusion: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer.

En este trabajo se analiza el grado de resiliencia, de motivación de logro y de satisfacción con la carrera elegida que presentaron los estudiantes de la asignatura Física I de las carreras de Bioquímica y Farmacia de la Facultad de Ciencias Exactas, Químicas y Naturales de la Universidad Nacional de Misiones. Para la recolección de datos se utilizaron encuestas anónimas a través de la plataforma Google, que luego fueron analizados estadísticamente. Los resultados obtenidos dan cuenta que los estudiantes se perciben altamente resilientes y poseen un alto grado de satisfacción con la carrera que eligieron. El análisis de la variable motivación de logros demostró que existe una gran brecha entre sus expectativas respecto a las calificaciones y los resultados de las instancias evaluativas.

In recent years, environmental issues have become the focus of societal concerns. In this context, the business world has been consolidating a form of green marketing management that merely conveys ambiguous or misleading messages rather than reflecting environmentally friendly business practices. This phenomenon is called greenwashing. This systematic review identifies and analyses the relationship between greenwashing and education (and at the more specific level of environmental education or education for sustainable development) in the academic literature. The sample consists of 20 papers retrieved from different databases using a systematic search strategy. As a result, an analysis of greenwashing trends in relation to education and its main approaches is presented: greenwashing literacy as an avoidance tool, the presence of the phenomenon in higher education institutions or in resources for educating, tools for identifying misleading green advertising and education, and anti-greenwashing educational proposals. Finally, some recommendations for identification and avoidance are presented.