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Attending to heartbeats for interoceptive awareness initiates distinct electrophysiological responses synchronized with the R-peaks of an electrocardiogram (ECG), such as the heartbeat-evoked potential (HEP). Beyond HEP, this study proposes heartbeat-related spectral perturbation (HRSP), a time-frequency map of the R-peak locked electroencephalogram (EEG), and explores its characteristics in identifying interoceptive attention states using a classification approach. HRSPs of EEG brain components specified by independent component analysis (ICA) were used for the offline and online classification of interoceptive states. A convolutional neural network (CNN) designed specifically for HRSP was applied to publicly available data from a binary-state experiment (attending to self-heartbeats and white noise) and data from our four-state classification experiment (attending to self-heartbeats, white noise, time passage, and toe) with diverse input feature conditions of HRSP. From the dynamic state perspective, we evaluated the primary frequency bands of HRSP and the minimal number of averaging epochs required to reflect changing interoceptive attention states without compromising accuracy. We also assessed the utility of group ICA and models for classifying HRSP in new participants. The CNN for trial-by-trial HRSP with actual R-peaks demonstrated significantly higher classification accuracy than HRSP with sham, i.e., randomly positioned, R-peaks. Gradient-weighted class activation mapping highlighted the prominent role of theta and alpha bands between 200-600 ms post-R-peak-features absent in classifications using sham HRSPs. Online classification benefits from employing a group ICA and classification model, ensuring reliable accuracy without individual EEG precollection. These results suggest HRSP's potential to reflect interoceptive attention states, proposing transformative implications for clinical applications.

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OBJECTIVE: Does loneliness predict premature death? Much prior research suggests so, but this evidence draws primarily on populations from individualistic societies, such as North America and Western Europe. Here, we aimed to extend this evidence by testing a hypothesis that loneliness would predict greater mortality risk in collectivistic societies, where social interdependence is normatively sanctioned. METHOD: Using a harmonized dataset from two individualistic (England and the United States) and two collectivistic (Korea and Mexico) countries (combined N = 41,869), we tested whether cultural contexts moderate the extent to which loneliness predicts 10-year all-cause mortality. RESULTS: After adjustment of demographic variables and health behaviors, loneliness was associated with increased 10-year mortality in all four countries, with hazard ratios (HRs) of 1.13 in England, 1.21 in the United States and Mexico, and 1.51 in Korea. When health conditions were additionally controlled, this association became negligible in two individualistic countries, with HRs of 0.98 for both England and the United States. In contrast, the HR remained highly significant in Korea (HR = 1.27). Curiously, the mortality risk of loneliness in Mexico (HR = 1.03), another collectivistic country, was no different from the risks in England and the United States. CONCLUSIONS: When people feel that they are chronically isolated from social networks, this perception can be fatal in Korea, but it is less so in the other three countries. Discussion focuses on other cultural factors, besides the cultural dimension of individualism-collectivism, that may account for the current finding. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

RESUMEN

PURPOSE: This study aims to explore obesity-related behaviors (ORB) and health-related quality of life (HRQoL) in socioeconomically vulnerable children, while also examining potential associations between these variables. DESIGN AND METHODS: A total of 721 children enrolled in after-school care programs for socioeconomically vulnerable children participated in this study. Height (in cm) and weight (in kg) were measured directly by trained research assistants. ORB, including eating behaviors and physical activity, was assessed utilizing the Nutrition Quotient Questionnaire. HRQoL was measured utilizing the PedsQL™ 4.0. Data were analyzed using logistic regression. RESULTS: The findings revealed that participants exhibited lower levels of ORB and reduced HRQoL, particularly in the physical health dimension of HRQoL. Inadequate physical activity and poor dietary habits were strongly associated with a 2.625-fold (OR = 2.625, 95% CI = 1.867-3.691) and a 4.251-fold (OR = 4.251, 95% CI = 2.466-7.328) increase, respectively, in the likelihood of having low HRQoL. Surprisingly, the study did not find a significant link between ORB levels and obesity, and obesity status did not predict a higher probability of low HRQoL. CONCLUSIONS: This study underscores the need for tailored interventions designed specifically for children from socioeconomically vulnerable families to address their unique challenges. PRACTICE IMPLICATIONS: This research provides valuable insights for pediatric nurses and healthcare providers, highlighting the crucial role of promoting healthy ORB in socioeconomically vulnerable children to address disparities in childhood obesity and HRQoL.

Asunto(s)

Obesidad Infantil , Calidad de Vida , Poblaciones Vulnerables , Humanos , Masculino , Femenino , Estudios Transversales , Niño , Obesidad Infantil/prevención & control , Factores Socioeconómicos , Conductas Relacionadas con la Salud , Conducta Alimentaria , Encuestas y Cuestionarios , Ejercicio Físico

RESUMEN

Elderly people avoid eating red meat and dried meat product due to its texture and stiffness; they deprive them of rich sources of nutrients. In addition, food-related diseases are exponentially increasing due to using synthetic additives in food products. Therefore, this research aimed to develop semi-dried goat meat jerky considering geriatric preferences by using natural tenderizers and nitrate. Four treatments were formulated negative control (NC [synthetic nitrite without tenderizers]), positive control (PC [Swiss chard without tenderizers]), T1 (Swiss chard with pineapple powder), and T2 (Swiss chard with pineapple and tomato powder). T1 and T2 had higher processing yield, and rehydration capacity compared with NC and PC. The fat content of T1 and T2 was lower than the control groups. Moisture was significantly higher in T1, NC, and T2 than in PC (p < 0.05). T2 showed the lowest water activity (0.87), lowest shear force (4.82 kgf), and lowest total plate count (TPC). The lowest pH and thiobarbituric acid reactive substances (TBARS) were observed in T1 and T2. T1 showed the lowest lightness and the maximum redness (p < 0.05) while PC showed the lowest yellowness. During the storage period, moisture and pH decreased, and TPC and TBARS significantly increased whereas water activity is stable regardless of the treatment. The results of the myofibrillar fragmentation index (MFI) and sodium dodecyl sulfate-polyacrylamide gel revealed that T1 and T2 more effectively converted protein to polypeptides. In addition, tenderizers positively affected thrombogenicity, atherogenicity, and hypocholesterolemic/hypercholesterolemic indices. T2 observed the highest overall sensory acceptance by reducing goaty flavor. Overall, jerky treated with tenderizers is easily chewable and digestible for the elderly due to its tenderness and essential fatty acids that would be senior-friendly food.

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Transcription-coupled DNA repair (TCR) removes bulky DNA lesions impeding RNA polymerase II (RNAPII) transcription. Recent studies have outlined the stepwise assembly of TCR factors CSB, CSA, UVSSA, and TFIIH around lesion-stalled RNAPII. However, the mechanism and factors required for the transition to downstream repair steps, including RNAPII removal to provide repair proteins access to the DNA lesion, remain unclear. Here, we identify STK19 as a new TCR factor facilitating this transition. Loss of STK19 does not impact initial TCR complex assembly or RNAPII ubiquitylation but delays lesion-stalled RNAPII clearance, thereby interfering with the downstream repair reaction. Cryo-EM and mutational analysis reveal that STK19 associates with the TCR complex, positioning itself between RNAPII, UVSSA, and CSA. The structural insights and molecular modeling suggest that STK19 positions the ATPase subunits of TFIIH onto DNA in front of RNAPII. Together, these findings provide new insights into the factors and mechanisms required for TCR.

RESUMEN

An 8-year-old castrated male Maltese dog was presented with a urinary bladder mass, urolithiasis, and hematuria. A solitary, pedunculated, intraluminal mass on the caudodorsal wall was identified with extensive irregular bladder wall thickening, and the mass was surgically removed. Postoperative histopathology demonstrated a submucosal lesion comprising spindle cells with marked inflammatory cell infiltration, without malignant changes. Immunohistochemical staining revealed vimentin and desmin positivity in the mass. An inflammatory myofibroblastic tumor (IMT) was definitively diagnosed. No recurrence was observed during a 43-month follow-up period. Although IMTs are rare in dogs, they should be considered a differential diagnosis for mass-like urinary bladder lesions accompanying a chronic inflammatory disease process. Key clinical message: Canine IMT should be included in the differential diagnoses of bladder masses, especially when dogs exhibit chronic irritation and inflammation.

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Tumeur myofibroblastique inflammatoire de la vessie chez un chienUn chien maltais mâle castré de 8 ans a été présenté avec une masse à la vessie, une lithiase urinaire et une hématurie. Une masse intraluminale pédonculée solitaire sur la paroi caudodorsale a été identifiée avec un épaississement important et irrégulier de la paroi vésicale, et la masse a été retirée chirurgicalement. L'histopathologie postopératoire a mis en évidence une lésion à la sous-muqueuse comprenant des cellules fusiformes avec une infiltration cellulaire inflammatoire marquée, sans modification maligne. La coloration immunohistochimique a révélé une positivité à la vimentine et à la desmine dans la masse. Une tumeur myofibroblastique inflammatoire (IMT) a été définitivement diagnostiquée. Aucune récidive n'a été observée au cours d'une période de suivi de 43 mois. Bien que les IMT soient rares chez le chien, ils doivent être considérés comme un diagnostic différentiel des lésions de la vessie de type masse accompagnant un processus de maladie inflammatoire chronique.Message clinique clé:L'IMT canine doit être incluse dans les diagnostics différentiels des masses vésicales, en particulier lorsque les chiens présentent une irritation et une inflammation chroniques.(Traduit par Dr Serge Messier).

Asunto(s)

Enfermedades de los Perros , Neoplasias de la Vejiga Urinaria , Perros , Animales , Masculino , Enfermedades de los Perros/patología , Enfermedades de los Perros/cirugía , Enfermedades de los Perros/diagnóstico , Neoplasias de la Vejiga Urinaria/veterinaria , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de Tejido Muscular/veterinaria , Neoplasias de Tejido Muscular/patología , Neoplasias de Tejido Muscular/cirugía , Neoplasias de Tejido Muscular/diagnóstico , Diagnóstico Diferencial , Inflamación/veterinaria

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Hanwoo beef is in high demand because of its unique flavor, freshness, and high-fat content. However, the longer rearing period required to enhance marbling in Hanwoo cattle has adverse environmental consequences, such as greenhouse gas emissions and overall rearing costs. To address consumer preferences for leaner and healthier meat, the Korean meat industry has recently introduced Hanwoo heifer meat as an alternative source, but its quality traits are still unclear. Nevertheless, there is a limited body of research exploring the impact of Hanwoo gender (steer, heifer, and cow) and their corresponding slaughter ages on meat quality traits. This study looked into how gender affected the physicochemical and qualitative features of Hanwoo striploin at their respective slaughter ages. Results revealed that cow striploin has higher levels of moisture (66.81%) and protein (20.76%), whereas it contains lower levels of fat (10.66%) and cholesterol (34.66 mg/100 g). Regarding the physicochemical properties, cow striploin exhibited significantly lower shear force, color indexes, and soluble collagen (p < 0.05). However, chondroitin (1.19%) and muscle fiber area (1,545.23 µm2) were significantly higher in steer striploin than in heifer and cow (p < 0.05). Cow striploin exhibited significantly higher levels of oleic acid, unsaturated fatty acids (UFAs), and monounsaturated fatty acids (MUFAs) while having lower levels of eicosadienoic acid and atherogenic index compared to the other two groups. Cows and heifers had higher concentrations of amino acid metabolites than striploin from steers. Furthermore, bioactive metabolites such as carnitine and carnosine content were found higher in cow and heifer respectively. Overall, Hanwoo cattle gender influences the qualitative attributes of striploin; nevertheless, compared to steer and heifer striploin, cow striploin is a relatively good source of protein, fatty acid content, and metabolites conducive to a healthy diet.

RESUMEN

With the creation of a social distancing policy due to coronavirus disease 2019 (COVID-19), home visit workers are under mental stress as they are treated as the source of infection for COVID-19. Since door-to-door rental equipment examiners and gas inspectors must perform their duties even in the COVID-19 situation, they are being discriminated against so severely. The purpose of study was to examine the mediating role of perceived stress on the relationship between risk perception and fear. Data was collected data through labor unions among 275 home visiting workers who examine rental home appliance equipment or inspecting gas. On-line survey was conducted to assess COVID-19 risk perception, fear, perceived stress, and demographic characteristics. The data was analyzed using PROCESS Macro (Model 4). The results of the study showed that stress plays an important role in increasing COVID-19 fears when COVID-19 risk perception increases. Meanwhile, it was found that COVID-19 fear decreased when the level of perceived stress decreased. To reduce the impact of COVID-19 risk perception on COVID-19 fears, appropriate educational programs to reduce stress should be developed for home visit workers. Policymakers need to develop online or mobile Infectious disease education programs for COVID-19 risk at work and establish policies to apply legal education.

Asunto(s)

COVID-19 , Miedo , Estrés Psicológico , Humanos , COVID-19/psicología , COVID-19/epidemiología , COVID-19/prevención & control , Masculino , Femenino , Adulto , Miedo/psicología , Estrés Psicológico/psicología , Persona de Mediana Edad , SARS-CoV-2 , Encuestas y Cuestionarios , Visita Domiciliaria , Auxiliares de Salud a Domicilio/psicología , Estrés Laboral/psicología , Estrés Laboral/epidemiología

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Spinal cord injury (SCI) patients require continuous rehabilitation post-discharge to ensure optimal recovery. This study investigates the effectiveness of home-based virtual reality fitness training (VRFT) as a convenient and accessible rehabilitation method for SCI patients. This randomized, double-blind, multicenter trial will enroll 120 participants, assigning them to either an 8-week VRFT program (exercise group) or a control group engaging in regular daily activities. The outcomes measured include muscle function, cardiopulmonary fitness, body composition, and physical performance. Our study will determine the safety and feasibility of VRFT in a home setting for SCI patients and evaluate whether these patients can effectively participate in such a program post-discharge. The results of this study are expected to inform future exercise protocols for SCI rehabilitation, offering valuable insights into the utility of VRFT as a therapeutic tool.

RESUMEN

Old age is associated with a higher risk of dementia. Psychosocial characteristics frequently affect cognitive function; however, the exact mechanism underlying the effect of psychosocial factors on cognitive function is unclear. Therefore, this study aimed to investigate the effects of psychosocial characteristics on cognitive function. The participants comprised 4809 middle-aged and older (years 50+) adults. The analysis used data from the Korean Longitudinal Study of Aging from 2014 to 2018. The effects of neighborhood interaction, depression, life satisfaction, and economic activity on cognitive function were examined, and a linear mixed model analysis was performed to assess the change in cognitive function by year. A statistically significant association was found between neighborhood interaction and time. Additionally, cognitive function decreased in the presence of depression and with time. In men, significant interactions were found between depression and time and between economic activity and time. In women, significant interactions were found between life satisfaction and time. The findings indicate that since active neighborhood interaction positively affects cognitive function, it is necessary to develop various community-wide social activity programs for middle-aged and older adults. As depression is a risk factor for cognitive impairment, it is crucial to prevent cognitive decline through continuous management of depression. Given the positive effects of economic activity on cognitive function in men, it is essential to expand infrastructure to sustain economic activity by developing educational programs and creating job opportunities for middle-aged and older men.

Asunto(s)

Cognición , Depresión , Humanos , Masculino , Femenino , Estudios Longitudinales , Persona de Mediana Edad , República de Corea/epidemiología , Anciano , Depresión/epidemiología , Depresión/psicología , Satisfacción Personal , Disfunción Cognitiva/epidemiología , Disfunción Cognitiva/psicología , Características de la Residencia , Envejecimiento/psicología , Factores de Riesgo , Factores Sexuales , Anciano de 80 o más Años

RESUMEN

In our prior investigations, we elucidated the role of the tryptophan-to-tyrosine substitution at the 61st position in the nonstructural protein NSsW61Y in diminishing the interaction between nonstructural proteins (NSs) and nucleoprotein (NP), impeding viral replication. In this study, we focused on the involvement of NSs in replication via the modulation of autophagosomes. Initially, we examined the impact of NP expression levels, a marker for replication, upon the infection of HeLa cells with severe fever thrombocytopenia syndrome virus (SFTSV), with or without the inhibition of NP binding. Western blot analysis revealed a reduction in NP levels in NSsW61Y-expressing conditions. Furthermore, the expression levels of the canonical autophagosome markers p62 and LC3 decreased in HeLa cells expressing NSsW61Y, revealing the involvement of individual viral proteins on autophagy. Subsequent experiments confirmed that NSsW61Y perturbs autophagy flux, as evidenced by reduced levels of LC3B and p62 upon treatment with chloroquine, an inhibitor of autophagosome-lysosome fusion. LysoTracker staining demonstrated a decrease in lysosomes in cells expressing the NS mutant compared to those expressing wild-type NS. We further explored the mTOR-associated regulatory pathway, a key regulator affected by NS mutant expression. The observed inhibition of replication could be linked to conformational changes in the NSs, impairing their binding to NP and altering mTOR regulation, a crucial upstream signaling component in autophagy. These findings illuminate the intricate interplay between NSsW61Y and the suppression of host autophagy machinery, which is crucial for the generation of autophagosomes to facilitate viral replication.

Asunto(s)

Autofagosomas , Autofagia , Phlebovirus , Triptófano , Tirosina , Proteínas no Estructurales Virales , Replicación Viral , Humanos , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/genética , Replicación Viral/genética , Autofagosomas/metabolismo , Células HeLa , Phlebovirus/genética , Phlebovirus/fisiología , Phlebovirus/metabolismo , Autofagia/genética , Tirosina/metabolismo , Triptófano/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Mutación , Sustitución de Aminoácidos , Síndrome de Trombocitopenia Febril Grave/metabolismo , Síndrome de Trombocitopenia Febril Grave/virología , Síndrome de Trombocitopenia Febril Grave/genética , Lisosomas/metabolismo , Nucleoproteínas/metabolismo , Nucleoproteínas/genética

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BACKGROUND: Community design features, such as sidewalks and street crossings, present significant challenges for individuals with disabilities, hindering their physical performance and social integration. However, limited research has been conducted on the application of Universal Design (UD) to address these challenges, particularly concerning specific demographic groups and population cohorts. Understanding the influence of environmental features on physical performance is crucial for developing inclusive solutions like UD, which can enhance usability and social integration across diverse populations. OBJECTIVE: This study aims to bridge this gap by investigating the complex relationships between environmental barriers, health conditions, and routine activity performance. An index was developed to evaluate users' UD performance based on functional capacity, providing scientifically rigorous and objectively measured evidence of UD effectiveness in creating inclusive built environments. METHOD: Using data from the Problematic Activities Survey (PAS) conducted in the U.S., Canada, and Australia and targeting individuals with and without functional limitations, multinomial logit models were employed to estimate the probabilities of encountering performance problems. This analysis led to the development of the Problematic Performance Value (PPV) score. RESULTS: The results demonstrated significant disparities in PPVs across various health conditions, particularly concerning curb ramps. Individuals facing mobility issues in their legs/feet, arms/hands, or back/neck encounter more pronounced challenges, especially when curb ramps lack proper design elements. Similarly, individuals with vision impairments face heightened difficulties with traffic signals, particularly due to issues with audible signal systems. These findings underscore the importance of addressing micro-level environmental challenges to accommodate individuals with varying functional capacities effectively. CONCLUSIONS: By providing insights into the most problematic daily activities encountered by diverse populations, the PPV score serves as a valuable indicator for guiding environmental design improvements and promoting equitable space usage. This can be used to guide improved UD solutions and decide areas of concentration by providing generalized information on specific environmental features that contribute to user performance.

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Personas con Discapacidad , Humanos , Masculino , Adulto , Persona de Mediana Edad , Femenino , Anciano , Australia , Adulto Joven , Canadá , Adolescente , Estados Unidos , Rendimiento Físico Funcional , Entorno Construido , Planificación Ambiental , Estado de Salud

RESUMEN

Cortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons resulted in significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed a significant reduction in cortical diaschisis and activation of the corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo , Neuronas , Optogenética , Recuperación de la Función , Accidente Cerebrovascular , Animales , Optogenética/métodos , Ratas , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/terapia , Masculino , Neuronas/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Modelos Animales de Enfermedad , Ratas Sprague-Dawley

RESUMEN

(1) Background: Upper body pain, particularly in the limbs and shoulders, is a common symptom among patients with spinal cord injury (SCI) and wheelchair users. Despite the focus on resistance muscle training as a suitable intervention for SCI individuals, findings across different populations and conditions have been inconsistent. (2) Methods: We conducted a systematic review to elucidate the correlations among exercise interventions, muscle strength enhancement, and pain reduction. A comprehensive literature search was performed using the keywords "spinal cord injury," "pain," "exercise," "disability," "paraplegia," and "tetraplegia" across the DBpia, EMBASE, PubMed, and Science Direct databases. (3) Results: From 191 identified articles, 13 studies (1 from Korea and 12 from other countries) were selected for analysis. The results indicate that exercise interventions are effective in reducing pain in patients with SCI, with a particular emphasis on alleviating shoulder pain. (4) Conclusion: Exercise is essential for pain reduction in patients with SCI, especially those experiencing shoulder pain. However, there is a notable lack of experimental research focusing primarily on pain. The development of appropriate measurement instruments is crucial for the prevention and relief of pain in this patient population.

RESUMEN

Neuropathic pain is a debilitating condition caused by the hyperexcitability of spinal dorsal horn neurons and is often characterized by allodynia. Although neuron-independent mechanisms of hyperexcitability have been investigated, the contribution of astrocyte-neuron interactions remains unclear. Here, we show evidence of reactive astrocytes and their excessive GABA release in the spinal dorsal horn, which paradoxically leads to the tonic excitation of neighboring neurons in a neuropathic pain model. Using multiple electrophysiological methods, we demonstrated that neuronal hyperexcitability is attributed to both increased astrocytic GABA synthesis via monoamine oxidase B (MAOB) and the depolarized reversal potential of GABA-mediated currents (EGABA) via the downregulation of the neuronal K+/Cl- cotransporter KCC2. Furthermore, longitudinal 2-deoxy-2-[18F]-fluoro-D-glucose microPET imaging demonstrated increased regional glucose metabolism in the ipsilateral dorsal horn, reflecting neuronal hyperexcitability. Importantly, inhibiting MAOB restored the entire astrocytic GABA-mediated cascade and abrogated the increased glucose metabolism and mechanical allodynia. Overall, astrocytic GABA-mediated tonic excitation is critical for neuronal hyperexcitability, leading to mechanical allodynia and neuropathic pain.

Asunto(s)

Astrocitos , Glucosa , Neuralgia , Ácido gamma-Aminobutírico , Astrocitos/metabolismo , Animales , Neuralgia/metabolismo , Neuralgia/etiología , Glucosa/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Masculino , Ratones , Neuronas/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/etiología , Células del Asta Posterior/metabolismo , Monoaminooxidasa/metabolismo , Modelos Animales de Enfermedad , Ratas , Cotransportadores de K Cl

RESUMEN

BACKGROUND AND OBJECTIVE: This study aimed to assess and compare the pharmacokinetics, safety, and tolerability of a fixed-dose combination product (FDCP) comprising four different drugs (two antihypertensive drugs, amlodipine and losartan, and two lipid-lowering agents, ezetimibe and rosuvastatin) with their separate tablets. METHODS: A total of 60 participants were enrolled in this open-label, randomized, single-dose crossover study. Each participant received a single dose of FDCP and individual tablets during each period, with a 14-day washout period between the periods. The pharmacokinetic parameters of amlodipine, losartan, EXP3174 (an active metabolite of losartan), rosuvastatin, free ezetimibe, and total ezetimibe were evaluated and compared. RESULTS: The pharmacokinetic profiles of amlodipine, losartan, rosuvastatin, and ezetimibe after administration of the individual products were similar to those of FDCP. The geometric mean ratios and 90% confidence intervals for maximum concentration (Cmax) and area under the curve (AUC) of FDCP to individual tablets were within 0.8-1.25 for all six analytes. No clinically relevant changes were observed in the vital signs or physical, biochemical, hematological, electrocardiographic, or urinalysis findings during the study, and no serious adverse events were reported. CONCLUSION: This study demonstrated that a newly developed FDCP containing amlodipine, losartan, ezetimibe, and rosuvastatin exhibited pharmacokinetic equivalence with the individual products and met the regulatory criteria. Both formulations were well tolerated. CLINICAL TRIAL REGISTRATION: This trial (NCT04322266) was retrospectively registered on 9 September 2019.

Asunto(s)

Amlodipino , Estudios Cruzados , Combinación de Medicamentos , Ezetimiba , Voluntarios Sanos , Losartán , Rosuvastatina Cálcica , Humanos , Rosuvastatina Cálcica/farmacocinética , Rosuvastatina Cálcica/administración & dosificación , Amlodipino/farmacocinética , Amlodipino/administración & dosificación , Amlodipino/efectos adversos , Masculino , Ezetimiba/farmacocinética , Ezetimiba/administración & dosificación , Losartán/farmacocinética , Losartán/administración & dosificación , Adulto , Femenino , Adulto Joven , Persona de Mediana Edad , Antihipertensivos/farmacocinética , Antihipertensivos/administración & dosificación , Antihipertensivos/efectos adversos , Comprimidos , Anticolesterolemiantes/farmacocinética , Anticolesterolemiantes/administración & dosificación , Área Bajo la Curva

RESUMEN

An effective vaccine strategy is indispensable against infectious bronchitis virus (IBV) and fowl typhoid (FT), both of which threaten the poultry industry. This study demonstrates a vector system, pJHL270, designed to express antigens in prokaryotic and eukaryotic cells. The vector system stimulates immune responses via synchronized antigen presentation to MHC class-I and -II molecules to produce balanced Th1/Th2 responses. The vaccine antigens were crafted by selecting the consensus sequence of the N-terminal domain of the spike protein (S1-NTD) and a conserved immunogenic region of the nucleocapsid protein (N321-406 aa) from IBV strains circulating in South Korea. The vaccine antigen was cloned and transformed into a live-attenuated Salmonella Gallinarum (SG) strain, JOL2854 (∆lon, ∆cpxR, ∆rfaL, ∆pagL, ∆asd). Western blot analysis confirmed concurrent antigen expression in Salmonella and eukaryotic cells. Oral immunization with the SG-based IBV vaccine construct JOL2918 induced IBV antigen and Salmonella-specific humoral and cell-mediated immune responses in chickens. PBMCs collected from immunized chickens revealed that MHC class-I and -II expression had increased 3.3-fold and 2.5-fold, respectively, confirming MHC activation via bilateral antigen expression and presentation. Immunization induced neutralizing antibodies (NAbs) and reduced the viral load by 2-fold and 2.5-fold in the trachea and lungs, respectively. The immunized chickens exhibited multifaceted humoral, mucosal, and cell-mediated responses via parallel MHC class-I and -II activation as proof of a balanced Th1/Th2 immune response. The level of NAbs, viral load, and gross and histological analyses provide clear evidence that the construct provides protection against IBV and FT.

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Pollos , Infecciones por Coronavirus , Virus de la Bronquitis Infecciosa , Enfermedades de las Aves de Corral , Salmonella enterica , Vacunas Virales , Animales , Pollos/inmunología , Virus de la Bronquitis Infecciosa/inmunología , Enfermedades de las Aves de Corral/prevención & control , Enfermedades de las Aves de Corral/inmunología , Enfermedades de las Aves de Corral/virología , Infecciones por Coronavirus/veterinaria , Infecciones por Coronavirus/prevención & control , Infecciones por Coronavirus/virología , Infecciones por Coronavirus/inmunología , Salmonella enterica/inmunología , Vacunas Virales/inmunología , Serogrupo , Vectores Genéticos , Regiones Promotoras Genéticas , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/genética

RESUMEN

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan-Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Asunto(s)

Neoplasias de la Mama , Movimiento Celular , Proliferación Celular , Resistencia a Antineoplásicos , Regulación Neoplásica de la Expresión Génica , ARN Largo no Codificante , Tamoxifeno , Femenino , Humanos , Antineoplásicos Hormonales/farmacología , Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proliferación Celular/efectos de los fármacos , Regulación hacia Abajo/genética , Resistencia a Antineoplásicos/genética , Células MCF-7 , Invasividad Neoplásica , Pronóstico , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Tamoxifeno/farmacología , Tamoxifeno/uso terapéutico , Microambiente Tumoral/genética

RESUMEN

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by skin and internal organ fibrosis and obliterative vasculopathy. Few effective treatments are currently available for fibrosis in SSc, therefore, demand persists for novel therapies. Although use of Ginkgo biloba extract (GBE) has been reported to improve blood circulation and alleviate liver and lung fibrosis, its effect on skin fibrosis in SSc remains unclear. In this study, the effects and underlying mechanisms of GBE on skin fibrosis in bleomycin (BLM)-induced mouse model of SSc was investigated. GBE significantly reduced dermal thickness and protein levels of profibrotic factors in the BLM-induced SSc mouse model. Moreover, GBE inhibited the gene expression of profibrotic factors, such as COL1A1, α-SMA, and connective tissue growth factor (CTGF), in fibroblasts by suppressing transforming growth factor (TGF)-ß signaling. Furthermore, GBE inhibited the transdifferentiation of adipocytes into myofibroblasts. Thus, our findings suggest that GBE is a promising therapeutic candidate for the treatment of SSc.