anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin-like growth factor-II receptor α (IGF-IIRα) acts as a stress-inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF-IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)-induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF-IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF-IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy-related and inflammation-related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF-IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS-treated H9c2 cardiac myoblasts with IGF-IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis-related cardiac mechanisms. Our study suggests that under sepsis-like conditions in the heart with IGF-IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF-IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.
This work aimed to study the role and mechanism of SIRT5 regulation of ferroptosis in cerebral ischemia-reperfusion (I/R) injury. A model of middle cerebral artery occlusion in rats was prepared using the method of thread occlusion. The ferroptosis inhibitor was injected intraperitoneally while the SIRT5 interfering lentivirus were injected into the brain, and neurological disorders were scored in the rats. TTC staining was used to detect infarct volume, and immunohistochemistry was used to detect the expression of SIRT5 in tissues. Rat hippocampal neuronal cells H19-7 were transduced with SIRT5 interfering lentivirus and ferroptosis was induced using erastin. The CCK8 detection kit was used to detect cell viability. Commercial kits were used to detect levels of iron ions, ROS, MDA, SOD, and inflammatory factor (TNF-α and IL-6) in brain tissue or cell supernatant. Western blot was used to detect the expression changes of ferroptosis related proteins GPX4, Nrf2, and HO-1 in tissues or cells. Compared with the sham group, the MCAO model group showed higher levels of neurological impairment score, increased cerebral infarction volume, iron ions, inflammatory factors, and oxidative stress levels in rats. Compared with the MCAO group, the MCAO + fer-1 group exhibited lower levels of neurological impairment scores, cerebral infarction volume, decreased iron ions, inflammatory factors, and oxidative stress levels in rats. Meanwhile, compared with the MCAO + DMSO/LV-shRNA group, the MCAO + fer-1/LV-shSIRT5 group showed a significant decrease in neurological impairment scores, cerebral infarction volume, iron ions, inflammatory factors, and oxidative stress levels in rats. In vitro experiments have found that LV-shSIRT5 can prevent erastin-induced cell ferroptosis. In summary, SIRT5 regulates ferroptosis through the Nrf2/HO-1 signaling axis to participate in ischemia-reperfusion injury in ischemic stroke.
Spinal cord contusion injury results in Wallerian degeneration of spinal cord axonal tracts, which are necessary for locomotor function. Axonal swelling and loss of axonal density at the contusion site, characteristic of Wallerian degeneration, commence within hours of injury. Tempol, a superoxide dismutase mimetic, was previously shown to reduce the loss of spinal cord white matter and improve locomotor function in an experimental model of spinal cord contusion, suggesting that tempol treatment might inhibit Wallerian degeneration of spinal cord axons. Here, we report that tempol partially inhibits Wallerian degeneration, resulting in improved locomotor recovery. We previously reported that Wallerian degeneration is reduced by inhibitors of aldose reductase (AR), which converts glucose to sorbitol in the polyol pathway. We observed that tempol inhibited sorbitol production in the injured spinal cord to the same extent as the AR inhibitor, sorbinil. Tempol also prevented post-contusion upregulation of AR (AKR1B10) protein expression within degenerating axons, as previously observed for AR inhibitors. Additionally, we hypothesized that tempol inhibits axonal degeneration by preventing loss of the glutathione pool due to polyol pathway activity. Consistent with our hypothesis, tempol treatment resulted in greater glutathione content in the injured spinal cord, which was correlated with increased expression and activity of gamma glutamyl cysteine ligase (γGCL; EC 6.3.2.2), the rate-limiting enzyme for glutathione synthesis. Administration of the γGCL inhibitor buthionine sulfoximine abolished all observed effects of tempol administration. Together, these results support a pathological role for polyol pathway activation in glutathione depletion, resulting in Wallerian degeneration after spinal cord injury (SCI). Interestingly, methylprednisolone, oxandrolone, and clenbuterol, which are known to spare axonal tracts after SCI, were equally effective in inhibiting polyol pathway activation. These results suggest that prevention of AR activation is a common target of many disparate post-SCI interventions.
Hypertension is currently highly prevalent worldwide and serves as one of the significant risk factors for chronic diseases and mortality. Adult hypertension can be traced back to, as well as prevented starting in, childhood and adolescence. However, due to the lack of surveillance among children and adolescents, the prevalence and influencing factors of hypertension-related conditions have not been well described. Hence, a total of 67,947 children and adolescents aged 6 to 17 from China Nutrition and Health Surveillance (2015-2017) were enrolled to describe the weighted average blood pressure level and the weighted prevalence of hypertension, pre-hypertension, and their distribution and to analyze the risk factors for hypertension and pre-hypertension among Chinese children and adolescents at a nationwide level. In summary, the weighted mean values of systolic blood pressure and diastolic blood pressure were 111.8 (95% CI, 111.2-112.5) mmHg and 66.5 (95% CI, 66.0-67.0) mmHg, respectively. The weighted prevalence of hypertension and pre-hypertension was 24.9% and 17.1%, respectively. Moreover, general obesity, overweight, and central obesity served as risk factors for hypertension and pre-hypertension among Chinese children and adolescents. The current study indicated that the prevalence of hypertension and pre-hypertension in Chinese children and adolescents was at a high level. Moreover, blood pressure screening should be further intensified for children and adolescents at a high risk of being overweight or obese.
Particles of active substance are encapsulated by spraying them with a thermoplastic silicone copolymer in solution in an organic solvent or in an aqueous dispersion or emulsion and removing the solvent or water by drying with hot air. The spraying/drying process employed is, for example, the Wurster process. The copolymer employed can be made up of a succession of polydiorganosiloxane segments or blocks and of organic segments or blocks (polyesters, polyethers, polyurethanes, polystyrenes, and the like). It can also be a polydiorganosiloxane grafted with organic chains. The active substance is in the form of particles with a particle size of between 50 μm and 5 mm. It may be a catalyst, a perfume, a colorant, a cosmetic product, a medication, a plant-protection product, plant seeds, and the like. 
     The invention is especially useful for controlling the release of active substance in an aqueous medium.
BACKGROUND: Glucocorticoids (GC) are the standard treatment for giant cell arteritis (GCA), even though they are associated with adverse side effects and high relapse rates. Tocilizumab (TCZ), an interleukin-6 receptor antagonist, has shown promise in sustaining remission and reducing the cumulative GC dosage, but it increases the risk of infections and is expensive. After discontinuation of TCZ, only about half of patients remain in remission. Additionally, only few studies have been conducted looking at remission maintenance, highlighting the need for alternative strategies to maintain remission in GCA. Methotrexate (MTX) has been shown to significantly decrease the risk of relapse in new-onset GCA and is already a proven safe drug in many rheumatologic diseases.
METHODS: This study aims to evaluate the efficacy and safety of MTX in maintaining remission in patients with GCA who have previously been treated with GC and at least 6 months with TCZ. We hypothesize that MTX can maintain remission in GCA patients, who have achieved stable remission after treatment with GC and TCZ, and prevent the occurrence of relapses. The study design is a monocentric, randomized, double-blind, placebo-controlled, parallel-group phase II trial randomizing 40 GCA patients 1:1 into a MTX or placebo arm. Patients will receive 17.5 mg MTX/matching placebo weekly by subcutaneous injection for 12 months, with the possibility of dose reduction if clinically needed. A 6-month follow-up will take place. The primary endpoint is the time to first relapse in the MTX group versus placebo during the 12-month treatment period. Secondary outcomes include patient- and investigator-reported outcomes and laboratory findings, as well as the prevalence of aortitis, number of vasculitic vessels, and change in intima-media thickness during the study.
DISCUSSION: This is the first clinical trial evaluating remission maintenance of GCA with MTX after a previous treatment cycle with TCZ. Following the discontinuation of TCZ in GCA, MTX could be a safe and inexpensive drug.
TRIAL REGISTRATION: ClinicalTrials.gov, NCT05623592. Registered on 21 November 2022. EU Clinical Trials Register, 2022-501058-12-00. German Clinical Trials Register DRKS00030571.
Caudal protrusion of pelvic organs and dilatation and deviation of the rectum with perineal hernia (PH) have not previously been studied using CT, and it is not known how completely the changes normalize after PH repair. Objectives of this prospective experimental case series were to evaluate the dimensions and shape of the rectum and the volume, location, and other features (enhancement pattern, presence of cysts, and mineralizations) of the prostate of 66 dogs on CT before and 3 months after PH repair. The rectal cross-sectional areas were measured at intrapelvic and caudal locations, and the shape was categorized as straight, deviated, flexure, or caudal fold on dorsal images. According to paired samples t-tests, the caudal rectal dimensions were significantly larger (P < .001) than the intrapelvic dimensions both before and 3 months after PH repair, and according to linear mixed models, the intrapelvic dimensions increased significantly (P < .001) after repair. Before PH repair, the most common rectal shape was flexure (69.2%); after repair, the number of dogs having a straight rectum increased significantly (P < .001) according to the McNemar paired-samples proportion test. We were also able to show that rectal dimensions increased after PH repair despite straightening in most dogs. According to the linear mixed model, prostate ratio volume, and according to Wilcoxon signed ranks test, the number of prostates with intraprostatic cysts decreased significantly (both P < .001) after PH repair, but the proportion of prostates located in the caudal or perineal area did not. Small mineralizations remained in some dogs.
Subjects with Mild cognitive impairment (MCI) or Subjective Cognitive Impairment (SCD) are eligible for this study. MCI often represents the earliest stages of Alzheimer's disease (AD), as individuals meeting criteria for MCI are subsequently diagnosed with AD at much higher rates than their cognitively normal elderly peers. Subjects with MCI are at risk of developing AD, within 6 years. Subjects with SCD may be at risk to develop MCI. The study is stratified according to whether subjects have SCD or MCI. The goal of the current study is to determine whether dietary supplementation with a novel formulation of curcumin (a component of the curry spice turmeric), which is better absorbed and more efficiently transported into the brain, can alter biological and clinical markers associated with AD risk, and to determine whether the potential beneficial effects of curcumin supplementation are synergistic with aerobic exercise. The investigators will recruit 80 elderly participants meeting criteria for MCI. Over the second 6 months of the study, the curcumin and placebo groups will be further divided into groups receiving training in either aerobic or non-aerobic yoga to determine the synergism between curcumin supplementation and aerobic exercise. The effectiveness of these interventions will be measured using plasma samples (for expression of Alzheimer-related biomarkers), and neuropsychological, functional, and behavioral assessments (i.e. clinical measures) collected at baseline, 6 months, and 12 months after initiation of treatments, with a subset of participants receiving brain imaging at baseline and 6 months. Dosage is titered up two weeks prior to study start (1 capsule BID, first five days, then 2 capsules BID for five days, then 6 capsules BID for five days, then 8 capsules BID- study dosage). Over the first 6 months of the study, participants will be randomized into equal groups receiving dietary supplementation with either curcumin or placebo. Patients are stratified according to whether they have only subjective memory complaints without MCI versus those that have MCI. Over the second 6 months of the study, participants will be further randomized into equal groups receiving dietary supplementation with either curcumin or placebo.
PROBLEM TO BE SOLVED: To obtain a quaternary alkylamidoalditolammonium compd. which is expected to be used as a new cationic surfactant having low irritating properties and useful for cosmetics or hair-care compsns. by reacting an alkylamidoalditolamine with a quaternizing agent. SOLUTION: A quaternary alkylamidoalditolammonium compd. of formula I is obtd. by reacting 1 mol of a compd. of formula II (wherein Z is an aldityl or glycosylaldityl group; R1 and R2 are each a 1-4C alkyl or 2-4C hydroxyalkyl; R4 CO is a 2-22C aliph. acyl; and n is 1-4) with 0.95-3 mol of a quaternizing agent of formula III (wherein R3 is the same as R1 in formula II; and X is a halogen or SO3 -O-R3 ) at 0-130 deg.C in a solvent selected from among alcohols, ethers, and halohydrocarbons.
PURPOSE:To obtain an antiviral polysaccharide substance useful as a drug, a food additive, a feed and a functional food, by refining the substance comprising as the component thereof polysaccharides including specific contents and having specific properties from an extract of Spirulina with boiling water. CONSTITUTION:An antiviral polysaccharide substance refined from an extract of Spirulina with boiling water (1) is polysaccharides contg. rhamnose, glucose, fructose, ribose, galactose, xylose, mannose, glucuronic acid, and galacturonic acid; (2) shows an absorption at 480nm in a phenol-sulfuric acid reaction; and (3) has a mol.wt. of 250,000 to 300,000 as measured by a gel filtration method. The word 'Spirulina' means algae which belong to the genus of Spirulina, among which all species contg. an antiviral substance soluble in boiling water can be used. Use of algae which belong to Spirulina platensis, which have heretofore been used in many foods, is pref. in the above-mentioned polysaccharide substance as well.
This study have only one arm that is the CTLA-4/PD-1 antibodies expressing mesoCAR-T cells group. All patients with advanced solid tumors will take part in the screening, who matching all the conditions will be chosen for the treatment.New CAR-T cells are cultured from PBMC and returned to the patients by venous transfusion.
FIELD: medicine, neurology, orthopedics. SUBSTANCE: the method deals with reflexotherapy and manual therapy and could be used to treat painful muscular syndromes of different etiology, for example, neurological manifestations of spinal osteochondrosis, pathology of articuloligamentous apparatus and some diseases of inner organs. The method deals with inactivation of trigger points by injecting per 2- 3 ml 50%-rheopolyglukin solution. The number of procedures corresponds to 3-5 seances at 1-d-long interval between each seance. The method increases anesthetization effect due to correction of hypotonic space of a trigger region. EFFECT: higher efficiency of therapy. 2 dwg, 4 tbl
BACKGROUND: Primary response genes play a pivotal role in translating short-lived stress signals into sustained adaptive responses. In this study, we investigated the involvement of ATL80, an E3 ubiquitin ligase, in the dynamics of gene expression following water deprivation stress. We observed that ATL80 is rapidly activated within minutes of water deprivation stress perception, reaching peak expression around 60 min before gradually declining. ATL80, despite its post-translational regulation role, emerged as a key player in modulating early gene expression responses to water deprivation stress.
RESULTS: The impact of ATL80 on gene expression was assessed using a time-course microarray analysis (0, 15, 30, 60, and 120 min), revealing a burst of differentially expressed genes, many of which were associated with various stress responses. In addition, the diversity of early modulation of gene expression in response to water deprivation stress was significantly abolished in the atl80 mutant compared to wild-type plants. A subset of 73 genes that exhibited a similar expression pattern to ATL80 was identified. Among them, several are linked to stress responses, including ERF/AP2 and WRKY transcription factors, calcium signaling genes, MAP kinases, and signaling peptides. Promoter analysis predicts enrichment of binding sites for CAMTA1 and CAMTA5, which are known regulators of rapid stress responses. Furthermore, we have identified a group of differentially expressed ERF/AP2 transcription factors, proteins associated with folding and refolding, as well as pinpointed core module genes which are known to play roles in retrograde signaling pathways that cross-referenced with the early ATL80 transcriptome.
CONCLUSIONS: Based on these findings, we propose that ATL80 may target one or more components within the retrograde signaling pathways for degradation. In essence, ATL80 serves as a bridge connecting these signaling pathways and effectively functions as an alarm signal.
OBJECTIVE: Alzheimer's disease (AD) is believed to be more common in African Americans (AA), but biomarker studies in AA populations are limited. This report represents the largest study to date examining cerebrospinal fluid AD biomarkers in AA individuals.
METHODS: We analyzed 3,006 cerebrospinal fluid samples from controls, AD cases, and non-AD cases, including 495 (16.5%) self-identified black/AA and 2,456 (81.7%) white/European individuals using cutoffs derived from the Alzheimer's Disease Neuroimaging Initiative, and using a data-driven multivariate Gaussian mixture of regressions.
RESULTS: Distinct effects of race were found in different groups. Total Tauand phospho181-Tau were lower among AA individuals in all groups (p < 0.0001), and Aβ42 was markedly lower in AA controls compared with white controls (p < 0.0001). Gaussian mixture of regressions modeling of cerebrospinal fluid distributions incorporating adjustments for covariates revealed coefficient estimates for AA race comparable with 2-decade change in age. Using Alzheimer's Disease Neuroimaging Initiative cutoffs, fewer AA controls were classified as biomarker-positive asymptomatic AD (8.0% vs 13.4%). After adjusting for covariates, our Gaussian mixture of regressions model reduced this difference, but continued to predict lower prevalence of asymptomatic AD among AA controls (9.3% vs 13.5%).
INTERPRETATION: Although the risk of dementia is higher, data-driven modeling indicates lower frequency of asymptomatic AD in AA controls, suggesting that dementia among AA populations may not be driven by higher rates of AD. ANN NEUROL 2024;96:463-475.
All patients will receive Normosol or equivalent solution, 0.5 ml/kg/fasted hour IV (approximately from midnight to time of induction) during induction of anesthesia. All patients will then receive maintenance fluids consisting of Normosol or equivalent solution at 6 ml/kg/operative hour. Those patients randomized to the Liberal Arm will receive an additional Normosol bolus or equivalent solution equal to (another) 1.5 ml/kg/fasted hour IV (to bring the total to 2 ml/kg/fasted hour) plus an additional bolus of Normosol or equivalent solution 6ml/kg/operative hour to bring the hourly rate to 12ml/kg/operative hour with a maximum of 1000 ml/operative hour.
BACKGROUND: A significant percentage of patients with congenital heart disease surviving into adulthood will develop arrhythmias. These arrhythmias are associated with an increased risk of adverse events and death. We aimed to assess arrhythmia prevalence, risk factors, and associated health care usage in a large national cohort of patients with adult congenital heart disease.
METHODS AND RESULTS: Adults with a documented diagnosis of congenital heart disease, insured by Clalit and Maccabi health services between January 2007 and December 2011, were included. We assessed the associations between arrhythmia and subsequent hospitalization rates and death with mixed negative binomial and Cox proportional hazard models, respectively. Among 11 653 patients with adult congenital heart disease (median age, 47 years [interquartile range, 31-62]), 8.7% had a tachyarrhythmia at baseline, 1.5% had a conduction disturbance, and 0.5% had both. Among those without a baseline arrhythmia, 9.2% developed tachyarrhythmias, 0.9% developed a conduction disturbance, and 0.3% developed both during the study period. Compared with no arrhythmia (reference group), arrhythmia in the previous 6 months was associated with a higher multivariable adjusted hospitalization rate, 1.33-fold higher than the rate of the reference group (95% CI, 1.00-1.76) for ventricular arrhythmia, 1.27-fold higher (95% CI, 1.17-1.38) for atrial arrhythmias, and 1.33-fold higher (95% CI, 1.04-1.71) for atrioventricular block. Atrial tachyarrhythmias were associated with an adjusted mortality hazard ratio (HR) of 1.65 (95% CI, 1.44-2.94), and ventricular tachyarrhythmias with a >2-fold increase in mortality risk (HR, 2.06 [95% CI, 1.44-2.94]).
CONCLUSIONS: Arrhythmias are significant comorbidities in the adult congenital heart disease population and have a significant impact on health care usage and survival.
When cannabidiol and sirolimus are co-administered, closely monitor for an increase in sirolimus blood levels and for adverse reactions suggestive of sirolimus toxicity. A dose reduction of sirolimus should be considered as needed when sirolimus is co-administered with cannabidiol [see Dosage and Administration (Error! Hyperlink reference not valid.) and Drug Interactions (Error! Hyperlink reference not valid.)].