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OBJECTIVES: Mental health remains an unmet need among Chinese Americans. This study aims to identify specific needs and strategies that may address the needs. DESIGN: A total of 55 Chinese Americans consented and participated in online focus groups conducted in either Chinese or English using nominal group technique. Participants discussed the following questions, achieved themes, and provided ranking of themes in importance for each: (1) In general, what do people in the Chinese American community think about mental health or emotional well-being? (2) What have you found to be helpful for accessing mental health or emotional well-being services or care in the Chinese American population? And (3) What actions would you suggest to improve mental health and emotional well-being in the Chinese American population? RESULTS: Across the focus groups, we observed high consistency of top ranked themes including lack of knowledge and awareness, negative impression, lack of Chinese-speaking providers, and that the most helpful factor toward access to care was education and increased awareness. Seminars and trainings was the top actionable suggestion. CONCLUSION: The findings are consistent with previous findings and continue to show that Chinese Americans need more education and training and that providers who can speak the language and understand the culture would be very helpful to increase access to care. This study emphasizes addressing mental health disparities in the Chinese American community through awareness, tailored interventions, and barrier removal. Promoting equal access also underscores the need for ongoing assessment and responsive strategies.
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PURPOSE: To provide a method for the differential diagnosis of Robert's uterus with adenomyosis, a rare uterine malformation, and determine the best course of treatment. METHODS: A patient who had Robert's uterus with adenomyosis was admitted to our hospital in December 2022. We analyzed and summarized her case . RESULTS: Our patient complained of progressively worsening primary dysmenorrhea over the course of 3 years and lower abdominal pain lasting for 2 days. Her carbohydrate antigen 125 (CA125) level was 372.10 U/mL. Examinations conducted by several hospitals indicated that she had a single-horned uterus and a residual horned uterus, and our hospital's examination identified Robert's uterus. This malformation was corrected by open abdominal surgery. For the procedure, pelvic adhesions were first isolated, after which the closed uterine cavity and adenomyosis were resected. Subsequently, the left ovarian endometriosis cyst was resected and right tubal ligation was performed. After surgery, three injections of gonadotropin-releasing hormone A (GnRH-A) were administered, which lowered the patient's CA125 level to 14 U/mL and normalized her condition. CONCLUSION: We pioneered a new therapeutic approach for the treatment of Robert's uterus with adenomyosis. Some valuable references are provided for clinical practice.
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Adenomiosis , Útero , Humanos , Femenino , Adenomiosis/cirugía , Adenomiosis/complicaciones , Adenomiosis/diagnóstico , Útero/anomalías , Útero/cirugía , Adulto , Antígeno Ca-125/sangre , Anomalías Urogenitales/cirugía , Anomalías Urogenitales/diagnóstico , Anomalías Urogenitales/complicaciones , Hormona Liberadora de Gonadotropina/análogos & derivados , Hormona Liberadora de Gonadotropina/uso terapéutico , Dismenorrea/etiología , Endometriosis/cirugía , Endometriosis/complicaciones , Endometriosis/diagnósticoRESUMEN
BACKGROUND: The clinical features, liver histology, and genetic variants in 57 patients with moderate to severe immune-mediated liver injury from checkpoint inhibitors (ILICI) are presented. METHODS: Between 2010 and 2022, 57 high-causality ILICI cases were enrolled in the Drug-Induced Liver Injury Network. HLA and selected candidate gene variants were tested for association with ILICI risk compared to the general population and other DILI controls. RESULTS: The 57 high-causality cases were attributed to pembrolizumab (16), ipilimumab (15), ipilimumab and nivolumab (13), and other immune checkpoint inhibitors (13) and occurred at a median of 72 days after the first infusion. Median age was 57.8 years, 66% male, and 89% were non-Hispanic Whites. At DILI onset, 53% had hepatocellular, 35% mixed, and 15% cholestatic, with younger patients more likely to have hepatocellular injury. The incidence of ANA, smooth muscle antibody, and elevated IgG levels was low (17%, 23%, and 0%), but corticosteroids were given to 86%. Microgranulomas and hepatic steatosis were seen in 54% and 46% of the 26 liver biopsies, respectively. The HLA alleles associated with autoimmune hepatitis were not over-represented, but 2 host immune response genes (EDIL3 and SAMA5A) and 3 other genes (GABRP, SMAD3, and SLCO1B1) were associated with ILICI (OR: 2.08-2.4, p<0.01). CONCLUSIONS: ILICI typically arises within 12 weeks of initiating immunotherapy and is self-limited in most cases. Genetic variants involved in host T-cell regulation and drug disposition were identified, implicating these pathways in the pathogenesis of ILICI. If validated, these findings could lead to improved diagnostic instruments and possible treatments for ILICI.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Inhibidores de Puntos de Control Inmunológico , Humanos , Masculino , Persona de Mediana Edad , Femenino , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Anciano , Adulto , Variación Genética , Ipilimumab/efectos adversos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Nivolumab/efectos adversos , Nivolumab/uso terapéuticoRESUMEN
BACKGROUND: Azithromycin (AZ) is a widely used antibiotic. The aim of this study was to characterise the clinical features, outcomes, and HLA association in patients with drug-induced liver injury (DILI) due to AZ. METHODS: The clinical characteristics of individuals with definite, highly likely, or probable AZ-DILI enrolled in the US Drug-Induced Liver Injury Network (DILIN) were reviewed. HLA typing was performed using an Illumina MiSeq platform. The allele frequency (AF) of AZ-DILI cases was compared to population controls, other DILI cases, and other antibiotic-associated DILI cases. RESULTS: Thirty cases (4 definite, 14 highly likely, 12 probable) of AZ-DILI were enrolled between 2004 and 2022 with a median age of 46 years, 83% white, and 60% female. Median duration of AZ treatment was 5 days. Latency was 18.5 days. 73% were jaundiced at presentation. The injury pattern was hepatocellular in 60%, cholestatic in 27%, and mixed in 3%. Ten cases (33%) were severe or fatal; 90% of these were hepatocellular. Two patients required liver transplantation. One patient with chronic liver disease died of hepatic failure. Chronic liver injury developed in 17%, of which 80% had hepatocellular injury at onset. HLA-DQA1*03:01 was significantly more common in AZ-DILI versus population controls and amoxicillin-clavulanate DILI cases (AF: 0.29 vs. 0.11, p = 0.001 and 0.002, respectively). CONCLUSION: Azithromycin therapy can lead to rapid onset of severe hepatic morbidity and mortality in adult and paediatric populations. Hepatocellular injury and younger age were associated with worse outcomes. HLA-DQA1*03:01 was significantly more common in AZ cases compared to controls.
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Antibacterianos , Azitromicina , Enfermedad Hepática Inducida por Sustancias y Drogas , Humanos , Femenino , Masculino , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Persona de Mediana Edad , Azitromicina/efectos adversos , Adulto , Antibacterianos/efectos adversos , Anciano , Adulto Joven , Antígenos HLA/genética , Adolescente , Frecuencia de los Genes , Cadenas alfa de HLA-DQRESUMEN
Obesity is endemic to many developed countries. Overweight or obesity is associated with an increased risk of developing cancer. Dysfunctional adipose tissue alters cancer cell proliferation and migration; however, whether and how neoplastic epithelial cells communicate with adipose tissue and the underlying mechanism are less clear. BTG3 is a member of the anti-proliferative BTG/Tob family and functions as a tumor suppressor. Here, we demonstrated that BTG3 levels are downregulated in basal cell carcinoma and squamous cell carcinoma compared to normal skin tissue, and Btg3 knockout in mice augmented the development of papilloma in a mouse model of DMBA/TPA-induced skin carcinogenesis. Mechanistically, BTG3-knockout keratinocytes promoted adipocyte differentiation mainly through the release of IL1α, IL10, and CCL4, as a result of elevated NF-κB activity. These adipocytes produced CCL20 and FGF7 in a feedback loop to promote keratinocyte migration. Thus, our findings showcased the role of BTG3 in guarding the interplay between keratinocytes and adjacent adipocytes, and identified the underlying neoplastic molecular mediators that may serve as possible targets in the treatment of skin cancer.
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Adipocitos , Queratinocitos , Ratones Noqueados , Transducción de Señal , Neoplasias Cutáneas , Animales , Queratinocitos/metabolismo , Queratinocitos/patología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/metabolismo , Neoplasias Cutáneas/genética , Adipocitos/metabolismo , Adipocitos/patología , Ratones , Humanos , Carcinogénesis/patología , Carcinogénesis/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/patología , Diferenciación Celular , Proteínas Supresoras de Tumor/metabolismo , Proteínas Supresoras de Tumor/genética , Movimiento Celular , Factor 7 de Crecimiento de Fibroblastos/metabolismo , FN-kappa B/metabolismo , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Proteínas de Ciclo CelularRESUMEN
This study aimed to investigate the effects of germination and roasting on the flavor of quinoa. Firstly, the aroma of quinoa and germinated quinoa roasted under different conditions was analyzed using sensory evaluation and electronic nose (E-nose). Results showed that the best favorable aroma of quinoa and germinated quinoa was obtained when roasted at 160 °C for 15 min. Then, a total of 34 and 80 volatile organic compounds (VOCs) of quinoa and germinated quinoa roasted at 160 °C for 15 min were determined using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) and headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS), respectively. Germination and roasting effectively reduced the contents of VOCs that produced undesirable flavor. Moreover, germination improved the floral aromas, while roasting mainly produced caramel, cocoa, and roasted nut aromas of quinoa. This study indicated that germination and roasting treatments might serve as promising processing methods to improve the flavor of quinoa.
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We aimed to identify serum biomarkers that predict knee osteoarthritis (OA) before the appearance of radiographic abnormalities in a cohort of 200 women. As few as six serum peptides, corresponding to six proteins, reached AUC 77% probability to distinguish those who developed OA from age-matched individuals who did not develop OA up to 8 years later. Prediction based on these blood biomarkers was superior to traditional prediction based on age and BMI (AUC 51%) or knee pain (AUC 57%). These results identify a prolonged molecular derangement of joint tissue before the onset of radiographic OA abnormalities consistent with an unresolved acute phase response. Among all 24 protein biomarkers predicting incident knee OA, the majority (58%) also predicted knee OA progression, revealing the existence of a pathophysiological "OA continuum" based on considerable similarity in the molecular pathophysiology of the progression to incident OA and the progression of established OA.
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Biomarcadores , Progresión de la Enfermedad , Osteoartritis de la Rodilla , Humanos , Biomarcadores/sangre , Femenino , Osteoartritis de la Rodilla/metabolismo , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/fisiopatología , Persona de Mediana Edad , AncianoRESUMEN
Fuchs endothelial corneal dystrophy (FECD) is a leading indication for corneal transplantation, but its molecular etiology remains poorly understood. We performed genome-wide association studies (GWAS) of FECD in the Million Veteran Program followed by multi-ancestry meta-analysis with the previous largest FECD GWAS, for a total of 3970 cases and 333,794 controls. We confirm the previous four loci, and identify eight novel loci: SSBP3, THSD7A, LAMB1, PIDD1, RORA, HS3ST3B1, LAMA5, and COL18A1. We further confirm the TCF4 locus in GWAS for admixed African and Hispanic/Latino ancestries and show an enrichment of European-ancestry haplotypes at TCF4 in FECD cases. Among the novel associations are low frequency missense variants in laminin genes LAMA5 and LAMB1 which, together with previously reported LAMC1, form laminin-511 (LM511). AlphaFold 2 protein modeling, validated through homology, suggests that mutations at LAMA5 and LAMB1 may destabilize LM511 by altering inter-domain interactions or extracellular matrix binding. Finally, phenome-wide association scans and colocalization analyses suggest that the TCF4 CTG18.1 trinucleotide repeat expansion leads to dysregulation of ion transport in the corneal endothelium and has pleiotropic effects on renal function.
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Distrofia Endotelial de Fuchs , Humanos , Distrofia Endotelial de Fuchs/genética , Distrofia Endotelial de Fuchs/metabolismo , Estudio de Asociación del Genoma Completo , Factor de Transcripción 4/genética , Colágeno , Laminina/genéticaRESUMEN
Interfacial solar vapor generation (ISVG) is an emerging technology to alleviate the global freshwater crisis. However, high-cost, low freshwater collection rate, and salt-blockage issues significantly hinder the practical application of solar-driven desalination devices based on ISVG. Herein, with a low-cost copper plate (CP), nonwoven fabric (NWF), and insulating ethylene-vinyl acetate foam (EVA foam), a multistage device is elaborately fabricated for highly efficient simultaneous freshwater and salt collection. In the designed solar-driven device, a superhydrophobic copper plate (SH-CP) serves as the condensation layer, facilitating rapid mass and heat transfer through dropwise condensation. Moreover, the hydrophilic NWF is designed with rational hydrophobic zones and specific high-salinity solution outlets (Design-NWF) to act as the water evaporation layer and facilitate directional salt collection. As a result, the multistage evaporator with eight stages exhibits a high water collection rate of 2.25 kg m-2 h-1 under 1 sun irradiation. In addition, the desalination device based on the eight-stage evaporator obtains a water collection rate of 13.44 kg m-2 and a salt collection rate of 1.77 kg m-2 per day under natural irradiation. More importantly, it can maintain a steady production for 15 days without obvious performance decay. This bifunctional multistage device provides a feasible and efficient approach for simultaneous desalination and solute collection.
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Agua Dulce , Luz Solar , Salinidad , Purificación del AguaRESUMEN
Hybridizing aqueous electrolytes with organic co-solvents can effectively expand the voltage window of aqueous electrolytes while reducing salt usage, but most reported co-solvents are usually flammable and toxic, hardly achieving compatibility between safety and electrochemical performance. Here, a new non-flammable and non-toxic low-salt-concentration (1.85 m) aqueous electrolyte is reported using the green co-solvent isosorbide dimethyl ether (IDE). Owing to its unique 3D molecular structure, IDE can form a five-membered ring structure by binding the Li ion. The steric hindrance effect from IDE weakens its solvation ability, generating anion-participated solvation structures that produce a robust and uniform LiF-rich solid electrolyte interphase layer while containing elastic IDE-derived organics. Moreover, the multiple O atoms in IDE can effectively regulate the intermolecular hydrogen bonding networks, reducing H2O molecule activity and expanding the electrochemical window. Such unique solvation structures and optimized hydrogen bonding networks enabled by IDE effectively suppress electrode/electrolyte interfacial side reactions, achieving a 4.3 V voltage window. The as-developed Li4Ti5O12(LTO)||LiMn2O4(LMO) full cell delivers outstanding cycling performance over 450 cycles at 2 C. The proposed green hybrid aqueous electrolyte provides a new pathway for developing high-voltage aqueous lithium batteries.
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OBJECTIVE: To better understand the pathogenesis of knee osteoarthritis (OA) through identification of serum diagnostics. DESIGN: We conducted multiple reaction monitoring mass spectrometry analysis of 107 peptides in baseline sera of two cohorts: the Foundation for National Institutes of Health (NIH) (n = 596 Kellgren-Lawrence (KL) grade 1-3 knee OA participants); and the Johnston County Osteoarthritis Project (n = 127 multi-joint controls free of radiographic OA of the hands, hips, knees (bilateral KL=0), and spine). Data were split into (70%) training and (30%) testing sets. Diagnostic peptide and clinical data predictors were selected by random forest (RF); selection was based on association (p < 0.05) with OA status in multivariable logistic regression models. Model performance was based on area under the curve (AUC) of receiver operating characteristic (ROC) and precision-recall (PR) curves. RESULTS: RF selected 23 peptides (19 proteins) and body mass index (BMI) as diagnostic of OA. BMI weakly diagnosed OA (ROC-AUC 0.57, PR-AUC 0.812) and only symptomatic OA cases. ACTG was the strongest univariable predictor (ROC-AUC 0.705, PR-AUC 0.897). The final model (8 serum peptides) was highly diagnostic (ROC-AUC 0.833, 95% confidence interval [CI] 0.751, 0.905; PR-AUC 0.929, 95% CI 0.876, 0.973) in the testing set and equally diagnostic of non-symptomatic and symptomatic cases (AUCs 0.830-0.835), and not significantly improved with addition of BMI. The STRING database predicted multiple high confidence interactions of the 19 diagnostic OA proteins. CONCLUSIONS: No more than 8 serum protein biomarkers were required to discriminate knee OA from non-OA. These biomarkers lend strong support to the involvement and cross-talk of complement and coagulation pathways in the development of OA.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/patología , Proteómica , Biomarcadores , PéptidosRESUMEN
BACKGROUND: Intravenous vancomycin therapy can cause liver injury as well as "drug reaction with eosinophilia and systemic symptoms" (DRESS) syndrome. This study aimed to better define the clinical features and HLA associations of vancomycin-induced liver injury. OBJECTIVE: To describe clinical, biochemical, and temporal characteristics of vancomycin-induced liver injury. METHODS: Cases of liver injury with recent exposure to vancomycin who were enrolled in the US Drug-induced Liver Injury Network between 2004 and 2020 were assessed. Sequencing of HLA alleles was performed on stored blood samples. RESULTS: Among 1697 cases of drug-induced liver injury identified between 2004 and 2021, 9 (0.5%) were attributed to intravenous vancomycin. The 9 cases included 6 men, median age 60 years (range, 23-85 days), and treatment for 26 days (range, 1-34 days). The clinical presentation was DRESS syndrome in 8 patients, of whom 6 received corticosteroids. Liver injury varied from hepatocellular to cholestatic and from mild (n = 5) to fatal (n = 1). In survivors, liver injury and DRESS syndrome ultimately resolved. HLA typing demonstrated the HLA-A∗32:01 allele in 7 vancomycin cases (78%, all with DRESS syndrome), versus 1 of 81 cases (1.2%) exposed but not attributed to vancomycin, and 113 of 1708 cases (6.6%) without vancomycin exposure. The allele frequency in vancomycin cases was 0.44 compared with less than 0.04 in US populations. CONCLUSIONS: Vancomycin-induced liver injury is commonly associated with DRESS syndrome and linked to HLA-A∗32:01. HLA-A∗32:01 testing could be considered early to risk-stratify patients using long-term intravenous vancomycin therapy.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Síndrome de Hipersensibilidad a Medicamentos , Eosinofilia , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/complicaciones , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/tratamiento farmacológico , Síndrome de Hipersensibilidad a Medicamentos/tratamiento farmacológico , Eosinofilia/tratamiento farmacológico , Antígenos HLA-A , Vancomicina/efectos adversos , FemeninoRESUMEN
INTRODUCTION: To investigate human leukocyte antigen alleles associated with liver injury due to antiepileptic drugs (AEDs) in African Americans (AA). METHODS: In this study, 21 AA with AED drug-induced liver injury (DILI), 176 AA with DILI due to non-AEDs, and 5816 AA population controls were included. RESULTS: HLA-B*53:01 was significantly associated with aromatic AED-DILI (odds ratio: 4.52, 95% confidence interval: 2.42-8.44, P = 1.46 × 10 -5 ). Phenytoin DILI showed the strongest association with HLA-B*53:01 (odds ratio: 9.17; 95% confidence interval: 3.61-23.28, P = 1.1 × 10 -5 ). The HLA-B*53:01 allele was carried by 8 of 9 AA phenytoin DILI cases. DISCUSSION: HLA-B*53:01 is a significant risk factor of liver injury due to antiepileptics, particularly phenytoin, in AA.
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Anticonvulsivantes , Enfermedad Hepática Inducida por Sustancias y Drogas , Antígenos HLA-B , Humanos , Alelos , Anticonvulsivantes/efectos adversos , Negro o Afroamericano/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Antígenos HLA-B/genética , Fenitoína/efectos adversos , Factores de RiesgoRESUMEN
BACKGROUND: Deep hypothermia has been the standard for hypothermic circulatory arrest (HCA) during aortic arch surgery. However, centers worldwide have shifted toward lesser hypothermia with antegrade cerebral perfusion. This has been supported by retrospective data, but there has yet to be a multicenter, prospective randomized study comparing deep versus moderate hypothermia during HCA. METHODS: This was a randomized single-blind trial (GOT ICE [Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest]) of patients undergoing arch surgery with HCA plus antegrade cerebral perfusion at 4 US referral aortic centers (August 2016-December 2021). Patients were randomized to 1 of 3 hypothermia groups: DP, deep (≤20.0 °C); LM, low-moderate (20.1-24.0 °C); and HM, high-moderate (24.1-28.0 °C). The primary outcome was composite global cognitive change score between baseline and 4 weeks postoperatively. Analysis followed the intention-to-treat principle to evaluate if: (1) LM noninferior to DP on global cognitive change score; (2) DP superior to HM. The secondary outcomes were domain-specific cognitive change scores, neuroimaging findings, quality of life, and adverse events. RESULTS: A total of 308 patients consented; 282 met inclusion and were randomized. A total of 273 completed surgery, and 251 completed the 4-week follow-up (DP, 85 [34%]; LM, 80 [34%]; HM, 86 [34%]). Mean global cognitive change score from baseline to 4 weeks in the LM group was noninferior to the DP group; likewise, no significant difference was observed between DP and HM. Noninferiority of LM versus DP, and lack of difference between DP and HM, remained for domain-specific cognitive change scores, except structured verbal memory, with noninferiority of LM versus DP not established and structured verbal memory better preserved in DP versus HM (P = 0.036). There were no significant differences in structural or functional magnetic resonance imaging brain imaging between groups postoperatively. Regardless of temperature, patients who underwent HCA demonstrated significant reductions in cerebral gray matter volume, cortical thickness, and regional brain functional connectivity. Thirty-day in-hospital mortality, major morbidity, and quality of life were not different between groups. CONCLUSIONS: This randomized multicenter study evaluating arch surgery HCA temperature strategies found low-moderate hypothermia noninferior to traditional deep hypothermia on global cognitive change 4 weeks after surgery, although in secondary analysis, structured verbal memory was better preserved in the deep group. The verbal memory differences in the low- and high-moderate groups and structural and functional connectivity reductions from baseline merit further investigation and suggest opportunities to further optimize brain perfusion during HCA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02834065.
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Aorta Torácica , Hipotermia , Humanos , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Estudios Retrospectivos , Estudios Prospectivos , Calidad de Vida , Método Simple Ciego , Temperatura Corporal , Paro Circulatorio Inducido por Hipotermia Profunda/efectos adversos , Perfusión/efectos adversos , Perfusión/métodos , Cognición , Circulación Cerebrovascular , Resultado del TratamientoRESUMEN
Objective: To further validate a serum proteomics panel for predicting radiographic (structural) knee OA progression. Design: Serum peptides were targeted by multiple-reaction-monitoring mass spectrometry in the New York University cohort (n â= â104). Knee OA progression was defined as joint space narrowing ≥1 in the tibiofemoral compartment of one knee per study participant over a 24-month follow-up. The discriminative ability of an 11-peptide panel was evaluated by multivariable logistic regression and area under the receiver operating characteristic curve (AUC), without and with demographic characteristics of age, sex, and body mass index. The association of each peptide with OA progression was assessed by odds ratios (OR) in multivariable logistic regression models adjusted for demographics. Results: The cohort included 46 (44%) knee OA progressors. The panel of 11 peptides alone yielded AUC â= â0.66 (95% CI [0.55, 0.77]) for discriminating progressors from non-progressors; demographic traits alone yielded AUC â= â0.66 (95% CI [0.55, 0.77]). Together the 11 peptides and demographics yielded AUC â= â0.72 (95% CI [0.62, 0.83]). CRAC1 had the highest odds for predicting OA progression (OR 2.014, 95% CI [0.996, 4.296], p â= â0.058). Conclusions: We evaluated a parsimonious serum proteomic panel and found it to be a good discriminator of knee radiographic OA progression from non-progression. Since these biomarkers are quantifiable in serum, they could be deployed relatively easily to provide a simple, cost-effective strategy for identifying and monitoring individuals at high risk of knee OA progression.
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The objective of this study was to investigate the protective effects of quinoa protein (QPro) and its derived peptides (QPep) in dextran sulfate sodium (DSS)-induced colitis in mice. The results demonstrated that oral administration of QPro and QPep significantly alleviated colitis symptoms, including diarrhea, abdominal pain, bloody stools, weight loss, as well as reduced colonic shortening, inflammatory factor release, and intestinal barrier injury. Short-chain fatty acids (SCFAs) production rose as QPro and QPep modulated the composition of the intestinal microbiota. Western blotting results revealed that QPro and QPep also suppressed TLR4 levels and inhibited IκB-α and NF-κB phosphorylation in colon tissue, implying that the TLR4/IκB-α/NF-κB signaling pathway may be involved in the amelioration of QPro and QPep in DSS-induced colitis. These results indicate the potential of quinoa protein and its hydrolysate to serve as bioactive components in functional diets for intestinal health and to significantly lower intestinal inflammation.
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Chenopodium quinoa , Colitis Ulcerosa , Colitis , Microbioma Gastrointestinal , Animales , Ratones , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Colon , Sulfato de Dextran/efectos adversos , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Colitis Ulcerosa/metabolismoRESUMEN
This paper aimed to investigate the in vivo absorption of egg white hydrolysate (EWH) in rats and the transport route across the intestinal epithelium. Results showed that the level of plasma peptide-bound amino acid (PAA) of the EWH-supplemented rats (EWH-R) was determined to be 2012.18 ± 300.98 µmol/L, 10.72% higher than that of the control group, and was significantly positively correlated to that of EWH. Thirty-three egg white-derived peptides were successfully identified from the plasma of EWH-R, and 20 of them were found in both EWH-R plasma and EWH, indicating that these peptides tend to be absorbed through the intestinal epithelium in intact forms into the blood circulation. In addition, 637 up-regulated and 577 down-regulated genes in Caco-2 cells incubated with EWH were detected by RNA-sequencing and the clathrin-dependent endocytosis was the most enriched pathway in KEGG analysis. EWH significantly increased the mRNA levels of the key genes involved in the clathrin-dependent endocytosis but these changes would be inhibited by the clathrin-dependent endocytosis inhibitor of chlorpromazine. Moreover, the transepithelial transport of EWH across Caco-2 cell monolayers was significantly reduced by chlorpromazine. This study provided molecular-level evidence for the first time that clathrin-dependent endocytosis might be the main transport route of EWH in the intestinal epithelium.
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Clorpromazina , Clara de Huevo , Humanos , Ratas , Animales , Células CACO-2 , Clara de Huevo/química , Clorpromazina/farmacología , Mucosa Intestinal , Péptidos , Endocitosis , ClatrinaRESUMEN
SCOPE: The obesity epidemic continues to be a major global public health threat with limited effective treatments. Peptides are a group of promising bioactive molecules. Both in vivo and in vitro studies have demonstrated that quinoa has potential prebiotic benefits. Thus, the present study aims to investigate the influence of quinoa peptides (QP) consumption on obesity and its underlying mechanisms in high-fat diet (HFD)-induced mice. METHODS AND RESULTS: QP (1000 mg kg-1 day-1 ) is administered to HFD mice for 8 weeks, and is found to significantly reduce the body weight, and plasma levels of triacylglycerol (TG) and total cholesterol (TC) compare to the HFD group. In addition, QP significantly decreases lipid accumulation in the liver caused by HFD. The liver transcriptome analysis shows that the alleviation of QP on obesity is related to the PPAR signaling pathway. QP upregulates the expressions of PPAR-α and its related genes and downregulates the expressions of PPAR-γ and its downstream genes. Furthermore, QP remodels the community composition of gut microbiota by lowering the ratio of Firmicutes c Bacteroidetes (F/B). CONCLUSION: These findings suggest that QP consumption alleviates HFD-induced obesity by regulating the PPAR-α/γ signaling pathway in the liver and community structure of gut microbiota.
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Chenopodium quinoa , Microbioma Gastrointestinal , Animales , Ratones , Receptores Activados del Proliferador del Peroxisoma , Dieta Alta en Grasa/efectos adversos , Obesidad/tratamiento farmacológico , Obesidad/etiología , Péptidos/farmacología , Transducción de Señal , Ratones Endogámicos C57BLRESUMEN
Two-dimensional layered membranes with high and stable ion transport properties have various applications in nanofluidic devices; however, their construction remains a considerable challenge. Herein, we develop a superstable aramid nanofiber/graphite composite membrane with numerous one-dimensional and two-dimensional nano-confined interspaces for ultrafast ion transport. The fabricated flexible and scalable membrane exhibits high tensile strength (â¼115.3 MPa) even after immersion in water for 90 days. Further, the aramid nanofiber/graphite conductor features the surface-charge-governed ion transport behavior. The ionic conductivity of the membrane at a low potassium chloride concentration of 10-4 mol/L can be enhanced by 16 times that of the bulk counterpart. More importantly, its structure and ionic conductivity remain unchanged even after immersion in different harsh solutions (e.g., acid, base, and ethanol) for over 30 days. Molecular dynamics simulations reveal that the superstability of the membrane is attributable to the robust interchain interactions within the aramid nanofibers and the strong interfacial interactions between the aramid nanofibers and graphite nanosheets. This study highlights the superior structural stability of the proposed flexible and scalable aramid nanofiber/graphite composite membrane, which could be employed in advanced nanofluidic devices for application under extreme working environments.
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Li-S batteries with high energy density have the potential to become a viable alternative to Li-ion batteries. However, Li-S batteries still face several challenges, including the shuttle effect, low conversion kinetics, and Li dendrite growth. Natural clay minerals with porous structures, abundant Lewis-acid sites, high mechanical modulus, and versatile structural regulation show great potential for improving the performance of Li-S batteries. However, so far, relevant reviews focusing on the applications of natural clay minerals in Li-S batteries are still missing. To fill the gap, this review first presents an overview of the crystal structures of several natural clay minerals, including 1D (halloysites, attapulgites, and sepiolite), 2D (montmorillonite and vermiculite), and 3D (diatomite) structures, providing a theoretical basis for the application of natural clay minerals in Li-S batteries. Subsequently, research advancements in the natural clay-based energy materials in Li-S batteries have been comprehensively reviewed. Finally, the perspectives concerning the development of natural clay minerals and their applications in Li-S batteries are provided. We hope this review can provide timely and comprehensive information on the correlation between the structure and function of natural clay minerals in Li-S batteries and offer guidance for material selection and structure optimization of natural clay-based energy materials.