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Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/ßCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/ßCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/ßCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1ß, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/ßCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/ßCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1ß levels. The effects of the NEO/ßCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress.

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INTRODUCTION: This study investigates primary lateral sclerosis (PLS) as a rare manifestation of the presenilin 1 (PSEN1) NM_000021 c.851C > T p.Pro284Leu variant in three siblings of a Colombian family, outlining its clinical and neuropathological features and their relationship to Alzheimer's disease (AD). METHODS: Data were gathered using clinical evaluations, next-generation genetic sequencing, magnetic resonance imaging, biomarker analysis, and neuropathological examination. RESULTS: Carriers of the PSEN1 Pro284Leu variant exhibited classic PLS symptoms, including unilateral onset and bulbar syndromes, along with cognitive decline. Neuropathology showed corticospinal tract degeneration without amyloid beta deposition in spinal white matter. DISCUSSION: Our findings suggest an overlap between PLS and AD pathology in PSEN1 variant carriers. Results support considering PLS when diagnosing AD-related motor syndromes and including PSEN1 evaluation when performing genetic testing for PLS. The study highlights the need for further research to clarify the PLS-AD relationship, informing future treatments and clinical trials. HIGHLIGHTS: Pathogenic variants in presenilin 1 (PSEN1) can manifest as hereditary primary lateral sclerosis PSEN1 Pro284Leu carriers present motor, cognitive, and behavioral alterations  Cases had corticospinal tract microgliosis and severe Aß pathology in motor cortex  There was no evidence of amyloid deposition in the spinal cord white matter  All the neuropathology images are available for online visualization  Myelin pallor in the spinal cord is confined to the lateral corticospinal tracts.

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Background: The prevalence of autism spectrum disorder (ASD) has significantly risen in the past three decades, prompting researchers to explore the potential contributions of environmental factors during pregnancy to ASD development. One such factor of interest is gestational hypothyroxinemia (HTX), a frequent condition in pregnancy associated with cognitive impairments in the offspring. While retrospective human studies have linked gestational HTX to autistic traits, the cellular and molecular mechanisms underlying the development of ASD-like phenotypes remain poorly understood. This study used a mouse model of gestational HTX to evaluate ASD-like phenotypes in the offspring. Methods: To induce gestational HTX, pregnant mice were treated with 2-mercapto-1-methylimidazole (MMI), a thyroid hormones synthesis inhibitor, in the tap-drinking water from embryonic days (E) 10 to E14. A separate group received MMI along with a daily subcutaneous injection of T4, while the control group received regular tap water during the entire pregnancy. Female and male offspring underwent assessments for repetitive, anxious, and social behaviors from postnatal day (P) 55 to P64. On P65, mice were euthanized for the evaluation of ASD-related inflammatory markers in blood, spleen, and specific brain regions. Additionally, the expression of glutamatergic proteins (NLGN3 and HOMER1) was analyzed in the prefrontal cortex and hippocampus. Results: The HTX-offspring exhibited anxious-like behavior, a subordinate state, and impaired social interactions. Subsequently, both female and male HTX-offspring displayed elevated proinflammatory cytokines in blood, including IL-1ß, IL-6, IL-17A, and TNF-α, while only males showed reduced levels of IL-10. The spleen of HTX-offspring of both sexes showed increased Th17/Treg ratio and M1-like macrophages. In the prefrontal cortex and hippocampus of male HTX-offspring, elevated levels of IL-17A and reduced IL-10 were observed, accompanied by increased expression of hippocampal NLGN3 and HOMER1. All these observations were compared to those observed in the Control-offspring. Notably, the supplementation with T4 during the MMI treatment prevents the development of the observed phenotypes. Correlation analysis revealed an association between maternal T4 levels and specific ASD-like outcomes. Discussion: This study validates human observations, demonstrating for the first time that gestational HTX induces ASD-like phenotypes in the offspring, highlighting the need of monitoring thyroid function during pregnancy.

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Anti-Müllerian hormone (AMH) is proposed as a biomarker for fertility in cattle, yet this associative relationship appears to be influenced by heat stress (HS). The objective was to test serum AMH and AMH-related single nucleotide polymorphisms (SNPs) as markers potentially predictive of reproductive traits in dairy cows experiencing HS. The study included 300 Holstein cows that were genotyped using BovineSNP50 (54,000 SNP). A genome-wide association study was then executed. Nine intragenic SNPs within the pathways that influence the AMH gene were found important with multiple comparisons adjustment tests (p < 1.09 × 10-6). A further validation study was performed in an independent Holstein cattle population, which was divided into moderate (MH; n = 152) and severe heat-stressed (SH; n = 128) groups and then subjected to a summer reproductive management program. Serum AMH was confirmed as a predictor of fertility measures (p < 0.05) in MH but not in the SH group. Cows were genotyped, which revealed four SNPs as predictive markers for serum AMH (p < 0.01), reproductive traits (p < 0.01), and additional physiological variables (p < 0.05). These SNPs were in the genes AMH, IGFBP1, LGR5, and TLR4. In conclusion, serum AMH concentrations and AMH polymorphisms are proposed as predictive markers that can be used in conjunction with genomic breeding value approaches to improve reproductive performance in Holstein cows exposed to summer HS conditions.

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Introducción: La encefalopatía hepática mínima (EHM), es una enfermedad definida por la existencia de varias alteraciones neurofisiológicas, indetectables a la exploración neurológica y el examen clínico. Dentro de las estrategias diagnosticas para la EHM se contemplan las pruebas psicométricas (PHE), pero para su aplicación es indispensable la estandarización previamente en la población de estudio. Objetivo: El estudio se propuso determinar la tabla de la normalidad de las PHE para diagnosticar la encefalopatía hepática subclínica en una muestra de la población dominicana. Método: Se realizó un estudio descriptivo, prospectivo y transversal en un hospital de referencia nacional. Se analizaron 134 personas clasificados por grupos de edades (18-70 años de edad) y años de escolaridad. Se diseñó una tabla de 5x5. Se estudió la influencia de la edad, sexo, uso de espejuelo y de los años de escolarización en el rendimiento de cada uno de las PHE, para lo cual se utilizaron las siguientes pruebas estadísticas: análisis de varianza (ANOVA), prueba t de Student y regresión lineal. Resultado: La escolaridad y la edad fueron variables determinantes en el desempeño de las 5 pruebas psicométricas. Pero, la correlación univariable de la edad con el desempeño de la prueba TMS no hubo diferencias intra e inter grupos estadísticamente significativas (p>0.171). Conclusión: se confecciono la fórmula de predicción de resultados de los test psicométricos. Ninguno sobrepasó el punto de corte de la puntuación que oscila entre los -4 y los +2 puntos.

Introduction: Minimal hepatic encephalopathy (MHE) is a disease defined by the existence of several neurophysiological alterations, undetectable by neurological examination and clinical examination. Among the diagnostic strategies for EHM, psychometric tests (PHE) are contemplated, but for their application, prior standardization in the study population is essential. Objective: The study will need to determine the normality table of PHE to detect subclinical hepatic encephalopathy in a sample of the Dominican population. Method: A descriptive, prospective and cross-sectional study was carried out in a national reference hospital. 134 people classified by age groups (18-70 years of age) and years of schooling were analyzed. A 5x5 board is recommended. The influence of age, sex, use of glasses and years of schooling on the performance of each one of the PHEs was studied, for which the following statistical tests were used: analysis of variance (ANOVA), Student's t test and linear regression. Result: Schooling and age were determining variables in the performance of the 5 psychometric tests. But, the univariate coincidence of age with the performance of the TMS test, there were no statistically significant intra and inter group differences (p>0.171). Conclusion: the formula for predicting the results of the psychometric tests was made. None exceeded the cut-off point of the score that oscillates between -4 and +2 points.

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The control of ticks through vaccination offers a sustainable alternative to the use of chemicals that cause contamination and the selection of resistant tick strains. However, only a limited number of anti-tick vaccines have reached commercial realization. In this sense, an antigen effective against different tick species is a desirable target for developing such vaccines. A peptide derived from the tick P0 protein (pP0) conjugated to a carrier protein has been demonstrated to be effective against the Rhipicephalus microplus, Rhipicephalus sanguineus, and Amblyomma mixtum tick species. The aim of this work was to assess the efficacy of this peptide when conjugated to the Bm86 protein against Dermacentor nitens and Ixodes ricinus ticks. An RNAi experiment using P0 dsRNA from I. ricinus showed a dramatic reduction in the feeding of injected female ticks on guinea pigs. In the follow-up vaccination experiments, rabbits were immunized with the pP0-Bm86 conjugate and challenged simultaneously with larvae, nymphs, and the adults of I. ricinus ticks. In the same way, horses were immunized with the pP0-Bm86 conjugate and challenged with D. nitens larva. The pP0-Bm86 conjugate showed efficacies of 63% and 55% against I. ricinus and D. nitens ticks, respectively. These results, combined with previous reports of efficacy for this conjugate, show the promising potential for its development as a broad-spectrum anti-tick vaccine.

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Adequate iodine nutrition is fundamental for all humans and is critical during pregnancy and lactation due to iodine forms part of the structure of thyroid hormones (THs) and it is required for THs function. Iodine is a scarce micronutrient that must be obtained from the diet. Sufficient iodine can be found in the nature from seafood and given it is not frequently consumed by Chileans, public health policies state that table salt in Chile must be iodized. Health plans must be monitored to determine if the intake of iodine is being appropriated and the population has not fallen in deficiency or excess. The aim of this work was to evaluate iodine intake in 26 women at the third trimester of pregnancy. Pregnant women are resident from El Bosque a low-income County located in Santiago de Chile. These Chilean pregnant women were recruited by nutritionist at the Centros de Salud familiar (CESFAM). A 24 h dietary recall (24 h-DR) was applied to them to evaluate iodine intake. Samples of urine and blood were taken by health professionals to analyze parameters of thyroid function and to measure urine iodine concentration (UIC). The survey analysis showed that the iodine consumption in these pregnant women derived mainly from salt, bread and milk and not from seafood. The survey analysis indicated that iodine intake was above the requirements for pregnant women. However, the average UIC indicated that iodine intake was adequate, suggesting the need to find a better parameter to determine iodine intake in pregnant women.

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This research shows the development of a teleoperation system with an assistive robot (NAO) through a Kinect V2 sensor, a set of Meta Quest virtual reality glasses, and Nintendo Switch controllers (Joycons), with the use of the Robot Operating System (ROS) framework to implement the communication between devices. In this paper, two interchangeable operating models are proposed. An exclusive controller is used to control the robot's movement to perform assignments that require long-distance travel. Another teleoperation protocol uses the skeleton joints information readings by the Kinect sensor, the orientation of the Meta Quest, and the button press and thumbstick movements of the Joycons to control the arm joints and head of the assistive robot, and its movement in a limited area. They give image feedback to the operator in the VR glasses in a first-person perspective and retrieve the user's voice to be spoken by the assistive robot. Results are promising and can be used for educational and therapeutic purposes.

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In this study, three mono-dendronized ß-cyclodextrin (ßCD) derivatives (ßCD-1G, ßCD-2G, and ßCD-3G) were used as multitasking containers of curcumin (CUR) to influence its aqueous solubility and tautomerism, both of which are related to its biological activity. We evaluated the relevant physicochemical properties of these containers associated with their potential hosting capacity. All mono-dendronized derivatives exhibited enhanced solubility in different solvents, including water, in comparison with native ßCD. Gas-phase geometry optimizations by density functional theory (DFT) confirmed that none of the dendrons blocked the passage of CUR into the ßCD cavity, and depending on the generation, different preorganization scenarios were promoted before complexation. Phase solubility diagrams showed that all the dendronized containers have superior performance for solubilizing CUR compared to native ßCD. We proved that coprecipitation is most efficient than lyophilization for forming inclusion complexes (ICs) with dendronized containers. Even though ßCD-3G with the largest 3G dendron exhibited the highest CUR loading, the complexation of CUR with ßCD-2G provided the supramolecular system that contains CUR preferentially in its diketo tautomer, which is known for its antioxidant activity.

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Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the gliotransmitters released, and their mechanisms of action remain elusive. Here, we report that fear conditioning training elevated Cx43 hemichannel activity in astrocytes from the basolateral amygdala (BLA). The selective blockade of Cx43 hemichannels by microinfusion of TAT-Cx43L2 peptide into the BLA induced memory deficits 1 and 24 h after training, without affecting learning. The memory impairments were prevented by the co-injection of glutamate and D-serine, but not by the injection of either alone, suggesting a role for NMDA receptors (NMDAR). The incubation with TAT-Cx43L2 decreased NMDAR-mediated currents in BLA slices, effect that was also prevented by the addition of glutamate and D-serine. NMDARs in primary neuronal cultures were unaffected by TAT-Cx43L2, ruling out direct effects of the peptide on NMDARs. Finally, we show that D-serine permeates through purified Cx43 hemichannels reconstituted in liposomes. We propose that the release of glutamate and D-serine from astrocytes through Cx43 hemichannels is necessary for the activation of post-synaptic NMDARs during training, to allow for the formation of short-term and subsequent long-term memory, but not for learning per se.

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