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Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.
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Estimulación Acústica , Vías Auditivas , Inhibición Prepulso , Reflejo de Sobresalto , Cuerpo Trapezoide , Animales , Inhibición Prepulso/fisiología , Masculino , Cuerpo Trapezoide/metabolismo , Cuerpo Trapezoide/fisiología , Vías Auditivas/fisiología , Vías Auditivas/metabolismo , Ratas Sprague-Dawley , Saporinas/metabolismo , Colina O-Acetiltransferasa/metabolismo , Neuronas Colinérgicas/metabolismo , Neuronas Colinérgicas/fisiología , Proteínas Inactivadoras de Ribosomas Tipo 1 , Potenciales Evocados Auditivos del Tronco Encefálico , Inmunotoxinas , Nervio Coclear/metabolismo , Nervio Coclear/fisiología , RatasRESUMEN
Summary: Background. Papular Urticaria (PU) is a cutaneous hypersensitivity disorder triggered by hematophagous arthropod bites. Despite being a common condition, especially in tropical environments, many knowledge gaps are observed for this disease. The main objective of this study was to investigate the patterns of humoral immune response to mosquito antigens in children with PU and establish a correlation between this response and the severity of clinical symptoms. Methods. An analytical cross-sectional observational study was carried out. Clinical and sociodemographic data and children's blood samples were collected to measure the specific antibodies from: 1. A. aegypti salivary gland antigens; 2. A. aegypti whole body antigens (both produced in the laboratory of the Center for Health Sciences at the Federal University of Rio de Janeiro). A PU severity score based on clinical data is proposed to correlate disease severity with antibody reactivity signatures. Results. According to the clinical data, 58.9% of children received high severity scores. A significant statistical correlation was found between patients with high PU severity score and the development of symptoms before the age of two (p = 0.0326) and high IgG4 anti-salivary gland antigens concentration (p less than 0.05). Conclusion. It is suggested that PU severity in children is associated with a high concentration of IgG4 anti-salivary gland antigens from Aedes aegypti. Further studies are recommended to deepen the understanding of the mechanisms involved.
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This study aimed to characterize the epidemiological aspects of PrEP use and barriers to accessing this prophylaxis. This cross-sectional study was conducted between January 2021 and April 2022, encompassing 140 PrEP users treated at the Testing and Counseling Center (CTA) in Campo Grande, Mato Grosso do Sul. Data on sociodemographic characteristics and factors associated with PrEP discontinuation were obtained using a standardized questionnaire. Most PrEP users were cisgender men (92.00%), predominantly white (51.00%), over 30 years of age (56.50%), homosexual-oriented (76.50%), and had a minimum of 12 years of education (77.50%). Approximately 60.00% admitted to inconsistent condom use in recent sexual encounters, primarily involving anal intercourse. Approximately 88.00% perceived themselves as at risk of contracting STIs in the upcoming year. Regarding new presentation forms, 54.00% indicated a willingness to use "on-demand PrEP," and 92.00% expressed interest in using "injectable PrEP." After 6 months of follow-up, 43.60% (95.00% CI: 35.50-52.00) discontinued PrEP use, primarily due to changes in sexual behavior (38.30%) and difficulties accessing healthcare services (21.28%). This study underscores the need to involve diverse key populations and highlights the significance of PrEP as an ongoing monitoring strategy for HIV/STI prevention in addition to the importance of incorporating new formulations such as daily oral PrEP into the Brazilian National Health System (SUS).
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Variability in snake venom composition is well-documented and crucial for understanding snake ecology and predicting snakebites. In this study, we characterize the venom composition and biological activities of newborn female and male Bothrops moojeni and their mother. Our results reveal significant differences between the venom of newborn females and males, demonstrating a broad and diverse range of proteins. The venoms of newborn females showed higher serine protease effects, increased hemorrhagic activity, and greater lethality compared to the venom of newborn males. However, no differences were observed in phospholipase A2 and coagulant activity. The differences in protein composition and toxic activities between maternal and neonatal venom, as well as between the venoms of newborn females and males, contribute to understanding the diverse outcomes of snakebites. These results underscore the importance of considering sex and ontogeny in understanding venom composition in snakes.
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Animales Recién Nacidos , Bothrops , Venenos de Crotálidos , Animales , Bothrops/clasificación , Bothrops/fisiología , Femenino , Masculino , Factores SexualesRESUMEN
BACKGROUND: Studies investigating the quality of the diet and dietary intake of children with Down syndrome (DS) are required because the features attributed to the syndrome can affect growth, development and quality of life. METHODS: This cross-sectional study was conducted with 77 Brazilian children with DS between 5 and 36 months of age receiving care at the multidisciplinary outpatient clinic of the University Hospital. Participants' sociodemographic, dietary and anthropometric data were collected from the care protocols. Dietary data were collected from 24-h recalls and dietary practices were assessed according to the WHO dietary guidelines. Associations between inadequate feeding practices and demographic variables were assessed using logistic regression models. RESULTS: Fruits, milk or infant formula, vegetables, beans and meat were among the five most consumed foods by the children investigated. Overall, we observed a high number of cases of early weaning (50.6%), low minimum dietary diversity (MDD; 40.3%), inadequate consistency for age (64.9%), early presence of ultra-processed foods (76.6%), sugars and sweets (33.8%) in the diet of the children with DS. In the associations of inadequate feeding practices by age group, low MDD [odds ratio (OR): 18.6; 95% confidence interval (CI): 3.4; 57.1] and inadequate consistency (OR: 6.65; 95% CI: 1.8; 24.7) were more frequent among children aged below 12 months while this relationship was inverse for early introduction of sugar and sweets (OR: 0.04; 95% CI: 0.01; 0.29). CONCLUSION: Our findings showed a high number of cases of inadequate dietary practices in children with DS investigated, which could adversely affect the long-term health of this population.
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Síndrome de Down , Conducta Alimentaria , Humanos , Síndrome de Down/epidemiología , Masculino , Brasil/epidemiología , Estudios Transversales , Femenino , Lactante , Preescolar , Conducta Alimentaria/fisiología , Dieta/estadística & datos numéricosRESUMEN
Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.
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Adenosina Trifosfato , Antineoplásicos , Cisplatino , Vaciamiento Gástrico , Condicionamiento Físico Animal , Ratas Wistar , Receptores Purinérgicos P2X7 , Animales , Cisplatino/farmacología , Masculino , Adenosina Trifosfato/metabolismo , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Receptores Purinérgicos P2X7/metabolismo , Condicionamiento Físico Animal/fisiología , Antineoplásicos/farmacología , Ratas , Antagonistas del Receptor Purinérgico P2X/farmacologíaRESUMEN
(In, Ga) alloy droplets are used to catalyse the growth of (In, Ga)As nanowires by molecular beam epitaxy on Si(111) substrates. The composition, morphology and optical properties of these nanowires can be tuned by the employed elemental fluxes. To incorporate more than 10% of In, a high In/(In+Ga) flux ratio above 0.7 is required. We report a maximum In content of almost 30% in bulk (In, Ga)As nanowires for an In/(In+Ga) flux ratio of 0.8. However, with increasing In/(In+Ga) flux ratio, the nanowire length and diameter are notably reduced. Using photoluminescence and cathodoluminescence spectroscopy on nanowires covered by a passivating (In, Al)As shell, two luminescence bands are observed. A significant segment of the nanowires shows homogeneous emission, with a wavelength corresponding to the In content in this segment, while the consumption of the catalyst droplet leads to a spectrally-shifted emission band at the top of the nanowires. The (In,Ga)As nanowires studied in this work provide a new approach for the integration of infrared emitters on Si platforms.
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Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.
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Extubation failure can result from different complications, mostly well described in the literature such as laryngeal edema. Airway obstruction by foreign bodies is a less frequent and unexpected complication and its detection remains a challenge to healthcare professionals. In this case-report, we describe a patient admitted in an intensive care unit following a motor vehicle accident and who underwent an extubation failure and tracheostomy placement due to a misdiagnosed obstruction of a foreign body in the upper airway. Thus, screening of foreign bodies should be considered with a careful interpretation of medical imagery and clinical evaluation in these patients. Finally, cuff leak test, ultrasonography and videolaryngoscopy can be important adjuvants to the identification of suspected foreign bodies.
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AIM: This study aimed to investigate the effects of caffeine on pathways associated with mitochondrial quality control and mitochondrial capacity during skeletal muscle regeneration, focusing on the role of Parkin, a key protein involved in mitophagy. METHODS: We used in vitro C2C12 myoblast during differentiation with and without caffeine in the medium, and we evaluated several markers of mitochondrial quality control pathways and myotube growth. In vivo experiments, we used C57BL/6J (WT) and Parkintm 1Shn lineage (Parkin-/- ) mice and injured tibial anterior muscle. The mice regenerated TA muscle for 3, 10, and 21 days with or without caffeine ingestion. TA muscle was used to analyze the protein content of several markers of mitochondrial quality pathways, muscle satellite cell differentiation, and protein synthesis. Furthermore, it analyzed mtDNA, mitochondrial respiration, and myofiber growth. RESULTS: C2C12 differentiation experiments showed that caffeine decreased Parkin content, potentially leading to increased DRP1 and PGC-1α content and altered mitochondrial population, thereby enhancing growth capacity. Using Parkin-/- mice, we found that caffeine intake during the regenerative process induces an increase in AMPKα phosphorylation and PGC-1α and TFAM content, changes that were partly Parkin-dependent. In addition, the absence of Parkin potentiates the ergogenic effect of caffeine by increasing mitochondrial capacity and myotube growth. Those effects are related to increased ATF4 content and activation of protein synthesis pathways, such as increased 4E-BP1 phosphorylation. CONCLUSION: These findings demonstrate that caffeine ingestion changes mitochondrial quality control during skeletal muscle regeneration, and Parkin is a central player in those mechanisms.
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Cafeína , Músculo Esquelético , Ratones , Animales , Cafeína/farmacología , Músculo Esquelético/metabolismo , Ratones Endogámicos C57BL , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , RegeneraciónRESUMEN
BACKGROUND: To investigate if maternal body mass index, diabetes and hypertension are associated with orofacial clefts. METHODS: Case-control study. Information from 53,188 live births with and without orofacial cleft registered at USA Vital Statistics Natality Birth Data between 2017 and 2021. Case group consisted of all affected live births diagnosed with orofacial clefts (13,297 cases). Comparison group consisted of 39,891 live births without clefts or any other congenital malformation. Information about orofacial cleft cases were compared with the comparison group. The unadjusted and adjusted Odds Ratios were estimated to evaluate the strength of association between mother's pre-pregnancy body mass index, maternal diabetes and hypertension and orofacial cleft occurrence, assuming a p valueâ<â0.05 and 95% confidence intervals (95% C.I.) for statistically significant differences. RESULTS: Mother's pre-pregnancy body mass index, maternal diabetes and maternal hypertension are conditions associated with an increased risk of orofacial cleft development in the child (ORâ=â1.08, pâ=â0.004, 95% C.I.â=â1.024-1.149; ORâ=â1.32, 95%, pâ=â0.000, 95% C.I.â=â1.202-1.444; and ORâ=â1.35, pâ=â0.000, 95% C.I.â=â1.239-1.484; respectively). Maternal ethnicity, sex of infant, and cigarette smoking pregnancy remained as covariates after adjustments in all logistic regression models. CONCLUSION: Due to the increased prevalence of obesity, diabetes, and hypertension, and also to their association with congenital malformations, such as clefts, it is recommended that mothers planning to become pregnant to follow healthy habits, maintain healthy weight, and be screened for possible diabetes or hypertension prior to conception and early in pregnancy.
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Labio Leporino , Fisura del Paladar , Diabetes Gestacional , Hipertensión , Femenino , Embarazo , Niño , Humanos , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Fisura del Paladar/complicaciones , Estudios de Casos y Controles , Índice de Masa Corporal , Factores de Riesgo , Diabetes Gestacional/epidemiología , Hipertensión/epidemiología , Hipertensión/complicacionesRESUMEN
ABSTRACTThe brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases.Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting.Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults.Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.
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Acetilcolinesterasa , Calidad de Vida , Ratones , Animales , Transportador de Glucosa de Tipo 3/metabolismo , Acetilcolinesterasa/metabolismo , Triglicéridos , Encéfalo/metabolismo , CogniciónRESUMEN
INTRODUCTION: The degree of conversion (DC) of resin cements can be affected by ceramics, and by the type of resin cement. The purpose was to evaluate the influence of thickness and translucencies of lithium disilicate ceramic on the DC of resin cements: two light-cure (Variolink LC; NX3 LC) and one dual-cure (NX3 Dual). METHODS: IPS e.max Press ceramic (A2) discs were prepared in 4 thicknesses (0.3, 0.5, 1.0, and 1.5 mm) and in 3 translucencies: HT (high translucency), LT (low translucency), and MO (medium opacity). Subsequently, 234 samples of resin cement (5 x 1 mm) were light-cured through those ceramic discs. The DC was assessed by Fourier Transform Infrared Spectroscopy (FTIR). RESULTS: Ceramic thicknesses decreased DC of NX3 Dual through HT-1.0 and HT 1.5 (p=0.005). Between translucencies, only MO-0.3 affected Variolink LC DC (p=0.018). There was difference among light- and dual-cured resin cements (p=0.001). CONCLUSION: Increasing thickness and opacity lead to a decrease in the DC of all resin cements, with a significantly lower DC value in NX3 Dual (HT-1.0; HT-1.5), and in Variolink LC (MO- 0.3). Light- and dual-cured resin cements were different among each other. NX3 Dual achieved a significantly lower value than its counterpart NX3 LC.
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Porcelana Dental , Cementos de Resina , Cementos de Resina/química , Ensayo de Materiales , Porcelana Dental/química , Cerámica/química , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
We propose a theoretical model to investigate the thermodynamics of single and coupled two-state ion channels, associated with mechanoelectrical transduction (MET) and hair cell biophysics. The modeling was based on the Tsallis nonextensive statistical mechanics. The choice for a nonextensive framework in modeling ion channels is encouraged on the fact that we take into account the presence of interactions or long-range correlations in the dynamics of single and coupled ion channels. However, the basic assumptions that support Boltzmann-Gibbs statistics, traditionally used to model ion channel dynamics, state that the system is formed by independent or weakly interacting elements. Despite being well studied in many biological systems, the literature has not yet addressed the study of both entropy and mutual information related to isolated or physically interacting pairs of MET channels. Inspired by hair cell biophysics, we show how the presence of nonextensivity, or subadditivity and superadditivity modulates the nonextensive entropy and mutual information as functions of stereocilia displacements. We also observe that the magnitude of the interaction between the two channels, given by a nonextensive parameter, influences the amplitude of the nonextensive joint entropy and mutual information as functions of the hair cell displacements. Finally, we show how nonextensivity regulates the current versus displacement curve for a single and a pair of interacting two-state channels. The present findings shed light on the thermodynamic process involved in the molecular mechanisms of the auditory system.
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Células Ciliadas Auditivas , Canales Iónicos , Biofisica , Entropía , TransductoresRESUMEN
Ruminal tympany (bloat) has long been an issue for large and small livestock operations. Though improvements in feedlot management practices have reduced its occurrence, it is still highly prevalent and is known to detrimentally affect animal performance, welfare, and in many instances, lead to animal death. Current decision support systems and diet formulation software omit the inclusion of bloat prediction based on animal performance. Here, we aim to predict bloat incidence in implanted and non-implanted feedlot steers from performance data comparing linear (LDB) and non-linear decision boundaries. Eighteen crossbred Angus × Hereford steers: BW (491.13 ± 25.78 kg) and age (12 ± 1 mo) were randomly distributed into implanted and non-implanted treatments. All animals were randomly assigned to one of two pens fit with automated monitoring systems for BW, freshwater intake, and water intake behavior: water intake event visit, no water intake event visit (NWIE), and time spent drinking. DM intake (DMI) was individually recorded from all animals through the Calan Gate system for 135 d (30 d adaptation, 105 d experimental diet). Incidences of bloat were recorded as bloat instances regardless of severity to ensure that early onset detection of bloat was recorded and properly identified in predictive models. Logistic regression with a binomial distribution and a logit link function was utilized to predict the incidences of bloat through LDB. Feature selection and penalization of coefficients were explored through L1 (sum of absolute values) and L2 (sum of squares) penalization to avoid overfitting of models. Additional NLDB and a non-parametric LDB are examined for prediction. Accuracy, specificity, and sensitivity were high for the models reported. No significant differences were observed between LDB and NLDB, with the highest specificity (predicting bloat) value of 0.820 for stepwise feature selection algorithms, and a value of 0.832 for the artificial neural network. Highest accuracy was 0.829 for ridge regression, and 0.847 for the random forest with hyperparameter tuning. DM intake, BW, and NWIE were the three most important variables for the prediction of feedlot bloat showing clear drops in DMI and BW and increases in NWIE when animals bloated. The lack of difference in predictive performance between LDB and NLDB highlights the often-overlooked concept that machine learning algorithms are not always the only/best modeling technique. Additionally, the models reported herein carry acceptable predictive performance for inclusion into management decisions that reduce bloat incidences in feedlot cattle.
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Alimentación Animal , Dieta , Bovinos , Animales , Alimentación Animal/análisis , Dieta/veterinaria , Recolección de DatosRESUMEN
The present study focused on investigating the antioxidant, antiglycation activity, digestive enzymes inhibition, bioaccessibility and hypoglycemic effect of C. arabica leaves extracts. The extracts deactivated the O2â¢-, ROOâ¢, H2O2, HOCl reactive oxygen species. Coffee leaves showed strong inhibition of α-glucosidase (IC50 = 40.30 µg mL-1) greater than the isolated metabolites and acarbose. There was also inhibition of pancreatic lipase (IC50 = 56.43 µg mL-1) in addition to a hypoglycemic effect in zebrafish similar to acarbose and metformin. With the exception of rutin, all biocompounds were detected at all stages of in vitro digestion. Finally, these results suggest that C. arabica leaf extracts possess antidiabetic and anti-obesity properties that can be attributed to the main metabolites and the synergistic action between them.Communicated by Ramaswamy H. Sarma.
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Antioxidantes , Coffea , Animales , Antioxidantes/farmacología , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Acarbosa , Peróxido de Hidrógeno , Pez CebraRESUMEN
Metabolic changes in immune cells contribute to both physiological and pathophysiological outcomes of immune reactions. Here, by comparing protein expression, transcriptome, and salivary metabolome profiles of uninfected and HIV+ individuals, we found perturbations of polyamine metabolism in the oral mucosa of HIV+ patients. Mechanistic studies using an in vitro human tonsil organoid infection model revealed that HIV infection of T cells also resulted in increased polyamine synthesis, which was dependent on the activities of caspase-1, IL-1ß, and ornithine decarboxylase-1. HIV-1 also led to a heightened expression of polyamine synthesis intermediates including ornithine decarboxylase-1 as well as an elevated dysfunctional regulatory T cell (TregDys)/T helper 17 (Th17) cell ratios. Blockade of caspase-1 and polyamine synthesis intermediates reversed the TregDys phenotype showing the direct role of polyamine pathway in altering T cell functions during HIV-1 infection. Lastly, oral mucosal TregDys/Th17 ratios and CD4 hyperactivation positively correlated with salivary putrescine levels, which were found to be elevated in the saliva of HIV+ patients. Thus, by revealing the role of aberrantly increased polyamine synthesis during HIV infection, our study unveils a mechanism by which chronic viral infections could drive distinct T cell effector programs and Treg dysfunction.
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Infecciones por VIH , Mucosa Bucal , Poliaminas , Humanos , Caspasas/inmunología , Infecciones por VIH/inmunología , Mucosa Bucal/inmunología , Ornitina Descarboxilasa/inmunología , Poliaminas/inmunología , Linfocitos T/inmunologíaRESUMEN
PURPOSE: Aging is associated with changes in glucose homeostasis related to both decreased insulin secretion and/or impaired insulin action, contributing to the high prevalence of type 2 diabetes (T2D) in the elderly population. Additionally, studies are showing that chronically high levels of circulating insulin can also lead to insulin resistance. In contrast, physical exercise has been a strategy used to improve insulin sensitivity and metabolic health. However, the molecular alterations resulting from the effects of physical exercise in the liver on age-related hyperinsulinemia conditions are not yet fully established. This study aimed to investigate the effects of 7 days of aerobic exercise on hepatic metabolism in aged hyperinsulinemic rats (i.e., Wistar and F344) and in Slc2a4+/- mice (hyperglycemic and hyperinsulinemic mice). RESULTS: Both aged models showed alterations in insulin and glucose tolerance, which were associated with essential changes in hepatic fat metabolism (lipogenesis, gluconeogenesis, and inflammation). In contrast, 7 days of physical exercise was efficient in improving whole-body glucose and insulin sensitivity, and hepatic metabolism. The Slc2a4+/- mice presented significant metabolic impairments (insulin resistance and hepatic fat accumulation) that were improved by short-term exercise training. In this scenario, high circulating insulin may be an important contributor to age-related insulin resistance and hepatic disarrangements in some specific conditions. CONCLUSION: In conclusion, our data demonstrated that short-term aerobic exercise was able to control mechanisms related to hepatic fat accumulation and insulin sensitivity in aged rodents. These effects could contribute to late-life metabolic health and prevent the development/progression of age-related T2D.