anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The invention comprises the cyclic polypeptide of the formula p I, <FORM:0928607/IV(a)/1> and the nonapeptide of the formula II, <FORM:0928607/IV(a)/2> in which R and R1 each represents a protective group for the sulphhydryl group, with the proviso that R and R1 need not be dissimilar, and R11 and R111 each represents a protective group for the amino group with the proviso that R11 and R111 need not be dissimilar and with the further proviso that all of R, R1, R11 and R111 may represent hydrogen atoms and pharmaceutical compositions containing the polypeptide. The groups R and R1 are particularly benzyl groups, R11 a carbobenzoxy group and R111 a p-toluenesulphonyl group. The compounds of the invention may be prepared by condensing the hexapeptide VIII, <FORM:0928607/IV(a)/3> after splitting off the carbobenzoxy group, with the azide of the tripeptide VIII, <FORM:0928607/IV(a)/4> to give the nonapeptide II, treating this with an alkali metal in liquid ammonia to yield the free nonapeptide and oxidising this to the cyclic polypeptide I by air or hydrogen peroxide. The hexapeptide VIII is prepared by condensing N-carbobenzoxy-L-glutaminyl-L-asparaginyl- S-benzyl- L-cysteinyl -azide with L-propyl-e -N-p-toluenesulphonyl- L-lysylgylcinamide prepared by hydrolysis of N-carbobenzoxy-L -prolyl-e -N- p-toluenesulphonyl-L-lysylglycinamide with hydrobromic acid. The tripeptide azide VIII is prepared by condensing N-carbobenzoxy- S-benzyl-L-cysteinyl-L-phenyl-alanine with L-phenylalanine methyl ester and converting the tripeptide ester in the azide with hydrazine. Pharmaceutical compositions comprise the cyclic polypeptide in addition to an inert carrier. The compositions may be formulated as solutions for injection or as nasal sprays. The peptide may be stored in the dry state when mixed with a water soluble carrier, e.g. sodium chloride, to increase its stability. The compositions have vasopressor activity.
FIELD: pharmaceutical engineering. SUBSTANCE: method involves working with fine dispersed powder of medical preparation having particle size less than 10 mcm and low yield point by agglomerating the fine dispersed powder of medical preparation in delivering the substance to worm feeder and producing agglomerates after its passing through the worm feeder. The produced agglomerates are spheroidized to obtain more consistent and compact bodies when compared to agglomerates produced by applying agglomeration process in worm feeder. The agglomerates are sorted according to their sizes and end product of uniform size is produced. The device has agglomerator unit having biconcave worms, spheroidizing unit being an agglomerating bin with scrubbers, unit for sorting agglomerates according to their sizes. Finished medical preparation is composed of agglomerates having specific surface of 2-20 m 2 /g. EFFECT: improved production process with no binding material needed; provided satisfactory viscosity and low cohesion coefficient in inhalation device. 13 cl, 7 dwg
The present application is directed to systems and methods providing a pathway configurable and executable via a pathway engine on a device. A device may establish a pathway configured via a pathway engine to execute on the device to monitor data points of a user and to generate actions based on monitoring of the data points. A monitor of the pathway engine may monitor data points of the user received by the device. The monitor may compare each value of the data points to the expected value and the predetermined threshold specified for the trigger condition. The pathway, based on the comparison, may determine that the trigger condition has been triggered. The pathway, responsive to the triggering of the trigger condition, may initiate an alert to identify the trigger condition and execution of the action specified by the pathway.
Worldwide more than half a million new cases of lung cancer are diagnosed annually. About 80% of these tumours are of non-small cell histological type. Surgery is the treatment of choice, but only about 20% of tumours are suitable for potentially curative resection. Concurrent chemoradiotherapy is the standard treatment for locally advanced NSCLC. When Iressa was used in the first-line treatment of advanced NSCLC with EGFR mutations positive, the 12-month rates of progression-free survival were 24.9%. Therefore, we speculate that the EGFR mutations in patients with locally advanced NSCLC, Gefitinib combined with radiotherapy may be better than chemoradiotherapy. We design the study to access the effect and safety of radiotherapy combined whth Iressa for patients with locally advanced non-small cell lung cancer with harboring active EGFR mutations.
BACKGROUND: Kawasaki disease (KD), an acute febrile illness and systemic vasculitis, is the leading cause of acquired heart disease in children in industrialized countries. KD leads to the development of coronary artery aneurysms (CAA) in affected children, which may persist for months and even years after the acute phase of the disease. There is an unmet need to characterize the immune and pathological mechanisms of the long-term complications of KD.
METHODS: We examined cardiovascular complications in the Lactobacillus casei cell wall extract (LCWE) mouse model of KD-like vasculitis over 4 months. The long-term immune, pathological, and functional changes occurring in cardiovascular lesions were characterized by histological examination, flow cytometric analysis, immunofluorescent staining of cardiovascular tissues, and transthoracic echocardiogram.
RESULTS: CAA and abdominal aorta dilations were detected up to 16 weeks following LCWE injection and initiation of acute vasculitis. We observed alterations in the composition of circulating immune cell profiles, such as increased monocyte frequencies in the acute phase of the disease and higher counts of neutrophils. We determined a positive correlation between circulating neutrophil and inflammatory monocyte counts and the severity of cardiovascular lesions early after LCWE injection. LCWE-induced KD-like vasculitis was associated with myocarditis and myocardial dysfunction, characterized by diminished ejection fraction and left ventricular remodeling, which worsened over time. We observed extensive fibrosis within the inflamed cardiac tissue early in the disease and myocardial fibrosis in later stages.
CONCLUSION: Our findings indicate that increased circulating neutrophil counts in the acute phase are a reliable predictor of cardiovascular inflammation severity in LCWE-injected mice. Furthermore, long-term cardiac complications stemming from inflammatory cell infiltrations in the aortic root and coronary arteries, myocardial dysfunction, and myocardial fibrosis persist over long periods and are still detected up to 16 weeks after LCWE injection.
Chronic pain is a universal public health problem with nearly one third of global human involved, which causes significant distressing personal burden. After painful stimulus, neurobiological changes occur not only in peripheral nervous system but also in central nervous system where somatosensory cortex is important for nociception. Being an ion channel, transient receptor potential vanilloid 1 (TRPV1) act as an inflammatory detector in the brain. Thymic stromal lymphopoietin (TSLP) is a potent neuroinflammation mediator after nerve injury. Bleomycin is applied to treat dermatologic diseases, and its administration elicits local painful sensation. However, whether bleomycin administration can cause chronic pain remains unknown. In the present study, we aimed to investigate how mice develop chronic pain after receiving repeated bleomycin administration. In addition, the relevant neurobiological brain changes after noxious stimuli were clarified. C57BL/6 mice aged five- to six-weeks were randomly classified into two group, PBS (normal) group and bleomycin group which bleomycin was intradermally administered to back five times a week over a three-week period. Calibrated forceps testing was used to measure mouse pain threshold. Western blots were used to assess neuroinflammatory response; immunofluorescence assay was used to measure the status of neuron apoptosis, glial reaction, and neuro-glial communication. Bleomycin administration induced mechanical nociception and activated both TRPV1 and TSLP/TSLPR/pSTAT5 signals in mouse somatosensory cortex. Through these pathways, bleomycin not only activates glial reaction but also causes neuronal apoptosis. TRPV1 and TSLP/TSLPR/pSTAT5 signaling had co-labeled each other by immunofluorescence assay. Taken together, our study provides a new chronic pain model by repeated intradermal bleomycin injection by activating TRPV1 and glial reaction-mediated neuroinflammation via TSLP/TSLPR/pSTAT5 signals.
PURPOSE: A system and a method for disclosing an injustice medical charge claim are provided to make a patient compare the medical treatment details of a medical organization with the medical treatment details of the patient by connecting to a server and to report the abnormality. CONSTITUTION: A personal information receiving module(26) receives the personal information of the patient by displaying an input module to a terminal of the patient and the medical organization. A personal information storing module(21) stores the received personal information. A claim details receiving module(27) receives the claim details of the patient. A providing module(25) provides the medical charge details of the patient to the terminal of the patient. A confirmation receiving module(28) enables a patient and an official organization to check the injustice claim details by providing the input module to input the confirmation of the injustice claims. An injustice claim details storing module(23) stores the injustice claim details received by the confirmation receiving module.
Doxorubicin (DOX) is a broad-spectrum antibiotic with potent anti-cancer activity. Nevertheless, despite having effective anti-neoplasm activity, its use has been clinically restricted due to its life-threatening side effects, such as cardiotoxicity. It is evident that betaine has anti-oxidant, and anti-inflammatory activity and has several beneficial effects, such as decreasing the amyloid-β generation, reducing obesity, improving steatosis and fibrosis, and activating AMP-activated protein kinase (AMPK). However, whether betaine could mitigate DOX-induced cardiomyopathy is still unexplored. Cardiomyopathy was induced in male Sprague Dawley rats using DOX (4 mg/kg dose with a cumulative dose of 20 mg/kg, i.p.). Further, betaine (200 and 400 mg/kg) was co-treated with DOX through oral gavage for 28 days. After the completion of the study, several biochemical, oxidative stress parameters, histopathology, western blotting, and qRT-PCR were performed. Betaine treatment significantly reduced CK-MB, LDH, SGOT, and triglyceride levels, which are associated with cardiotoxicity. DOX-induced increased oxidative stress was also mitigated by betaine intervention as the SOD, catalase, MDA, and nitrite levels were restored. The histopathological investigation also confirmed the cardioprotective effect of betaine against DOX-induced cardiomyopathy as the tissue injury was reversed. Further, molecular analysis revealed that betaine suppressed the DOX-induced increased expression of phospho-p53, phospho-p38 MAPK, NF-kB p65, and PINK 1 with an upregulation of AMPK and downregulation of Nrf2 expression. Interestingly, qRT-PCR experiments show that betaine treatment alleviates the DOX-induced increase in inflammatory (TNF-α, NLRP3, and IL-6) and fibrosis (TGF-β and Acta2) related gene expression, halting the cardiac injury. Interestingly, betaine also improves the mRNA expression of Nrf2, thus modulating the expression of antioxidant proteins and preventing oxidative damage. Here, we provide the first evidence that betaine treatment prevents DOX-induced cardiomyopathy by inhibiting oxidative stress, inflammation, and fibrosis by regulating AMPK/Nrf2/TGF-β expression. We believe that betaine can be utilized as a potential novel therapeutic strategy for preventing DOX-induced cardiotoxicity.
A randomized clinical trial research design is planned. Investigators will obtain baseline and final measures on the intervention and control groups. A sample of 60 adult Hispanic heart failure patients will be recruited. Each patient will either participate in the psychoeducational intervention or usual care. A repeated measures (longitudinal) analysis will be used to examine these aims by employing a linear mixed models approach. The basic analysis has one between subjects (fixed) factor, group, with 2 levels (education and control) and one repeated factor, time, with 2 levels (baseline and 12 months). This analysis allows for testing the main effect of group, main effect of time, and the group by time interaction. The potential benefit of improving heart failure knowledge and self-care in Hispanic heart failure patients is that these patients may better understand how to care for themselves. This study will provide data to examine the longer-term outcomes of emergency department visits and hospitalization events in Hispanic patients.
Malnutrition among critically ill older patients is a frequent problem in intensive care units (ICUs) and is associated with a higher risk of hospital/ICU length of stay (LOS) and mortality. The aim of this study was to evaluate malnutrition in older patients staying in an ICU using the hemoglobin, albumin, lymphocyte, platelet (HALP) score, modified nutrition risk in the critically Ill (mNUTRIC), prognostic nutritional index (PNI), and geriatric nutritional risk index (GNRI) and to determine the consistency between these tools and their association with clinical outcomes. This cross-sectional retrospective, observational, hospital-based study included 153 older patients (≥65 years of age), who were admitted to an internal medicine ICU. Sequential organ failure assessment (SOFA) scores and acute physiology and chronic health evaluation (APACHE) II were used to assess disease severity. Nutritional status was evaluated using mNUTRIC, GNRI, PNI, and HALP scores, and their association with ICU LOS and mortality was evaluated using ROC and regression analyses. The mortality rate of the patients was 43.1%. The risk of malnutrition was higher among non-survivors, with mNUTRIC scores showing a significant difference between the groups. The scores for all indices, except HALP, showed significant differences between the groups. APACHE-II, SOFA, and mNUTRIC were the strongest prognostic indices for ICU mortality, with mNUTRIC having the highest sensitivity and negative predictive value. The HALP score was not associated with ICU LOS or a significant prognostic factor for mortality. All indices except HALP were good indicators of clinical outcomes in the study population including older patients. Prospective studies in larger and specific patient populations are needed to draw a strict conclusion in this subject.
Participants in the intervention group will receive oxygen inhalation through a mask at a rate of 10 L/min at 1 absolute atmosphere pressure (1 ATA = 101.325 kPa) after randomization until adimisson to the hospital. Participants will subsequently receive standard diagnosis and treatment service according to the guidelines during hospitalization.
BACKGROUND AND OBJECTIVES: Sarcopenia has garnered extensive attention in clinical practice since its high prevalence and significant impact on clinical outcomes. Multiple organizations have published guidance documents on sarcopenia, offering evidence-based recommendations for clinical practice and/or research. We aimed to appraise the methodological quality of the included documents and synthesize available recommendations for the screening, diagnosis, and intervention of sarcopenia.
METHODS AND STUDY DESIGN: We conducted a search on PubMed, Embase, Scopus, Cochrane Library, China National Knowledge Infrastructure, guideline database, and guideline organizations and professional societies websites for clinical practices, consensus statements and position papers in terms of sarcopenia, muscle atrophy or muscle loss published before April 17, 2023. The AGREE II instrument was used by three independent reviewers to assess the methodological quality of these documents.
RESULTS: Thirty-six guidance documents published between 2010 and 2023 were included. Seven documents fulfilled ≥ 50% of all the AGREE II domains. Seven underwent a Delphi process and six graded the strength of the recommendations. The process of screening (n=21), early diagnosis of sarcopenia (n=12), diagnosis of sarcopenia and severe sarcopenia (n=10), and management (n=21) were increasingly recommended. SARC-F (n=14) was the most recommended screening tool, and the assessment of muscle function was considered the first step in diagnosing sarcopenia. The management strategy for both age-related and disease-related sarcopenia mainly focused on exercise and nutrition intervention.
CONCLUSIONS: The guidance documents have provided referential recommendations that have great guiding significance. But the inconsistency in recommendations and variation in methodological rigour suggests that high-quality evidence is lacking yet.
Method for introducing substituents in the 10-beta position of 19-nor-steroids consists of reacting 5-alpha 10-beta-epoxysteroids with nucleophilic reagents such as aliphatic and aromatic amines N-contg. aromatic heterocyclic compds. sulphonamides, H2S, hydrohalogen acids etc. in a polyhydric alcohol or other suitable solvent or in the nucleophilic reagent itself as solvent in the presence of proton - or Lewis acids as catalysts. Nucleophilic reagents of strong acidity are pref. used in teh form of their salts. The products possess oestrogenic gestagenic and anti-gonadotropin activity. Examples of such introduced 10-beta groups are mercapto, methanesulphonamido, butylamino, anilino, imidazolyl and 5-amino-tetrazolyl.
To evaluate the impact of CO2 fractional laser combined with recombinant human epidermal growth factor (rhEGF) gel on skin barrier in acne scar patients. In a retrospective analysis, we examined 105 acne scar patients admitted between July 2018 and August 2021. Of these, 51 received only CO2 fractional laser (control group), while 54 underwent a combination of CO2 fractional laser and rhEGF gel (observation group). We assessed treatment efficacy, symptom relief, skin barrier parameters, pre- and posttreatment inflammatory factors, adverse reactions, posttreatment quality of life, and patient satisfaction. The observation group exhibited a higher overall response rate, significantly shorter wound healing, scab formation, and scab detachment times. Additionally, this group showed increased stratum corneum water content, decreased pH, and transdermal water loss (TEWL), and reduced hypersensitive C-reactive protein and interleukin-6 expression posttreatment. Quality of life scores were higher, with fewer adverse reactions and greater treatment satisfaction. Combining CO2 fractional laser with rhEGF gel markedly improves acne scar treatment efficacy, enhances skin barrier function, reduces inflammation, and elevates quality of life. Its safety profile supports its broader clinical adoption.
BACKGROUND: Microplastics and nanoplastics (MNPs) are emerging as a potential risk factor for cardiovascular disease in preclinical studies. Direct evidence that this risk extends to humans is lacking.
METHODS: We conducted a prospective, multicenter, observational study involving patients who were undergoing carotid endarterectomy for asymptomatic carotid artery disease. The excised carotid plaque specimens were analyzed for the presence of MNPs with the use of pyrolysis-gas chromatography-mass spectrometry, stable isotope analysis, and electron microscopy. Inflammatory biomarkers were assessed with enzyme-linked immunosorbent assay and immunohistochemical assay. The primary end point was a composite of myocardial infarction, stroke, or death from any cause among patients who had evidence of MNPs in plaque as compared with patients with plaque that showed no evidence of MNPs.
RESULTS: A total of 304 patients were enrolled in the study, and 257 completed a mean (±SD) follow-up of 33.7±6.9 months. Polyethylene was detected in carotid artery plaque of 150 patients (58.4%), with a mean level of 21.7±24.5 μg per milligram of plaque; 31 patients (12.1%) also had measurable amounts of polyvinyl chloride, with a mean level of 5.2±2.4 μg per milligram of plaque. Electron microscopy revealed visible, jagged-edged foreign particles among plaque macrophages and scattered in the external debris. Radiographic examination showed that some of these particles included chlorine. Patients in whom MNPs were detected within the atheroma were at higher risk for a primary end-point event than those in whom these substances were not detected (hazard ratio, 4.53; 95% confidence interval, 2.00 to 10.27; P<0.001).
CONCLUSIONS: In this study, patients with carotid artery plaque in which MNPs were detected had a higher risk of a composite of myocardial infarction, stroke, or death from any cause at 34 months of follow-up than those in whom MNPs were not detected. (Funded by Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale and others; ClinicalTrials.gov number, NCT05900947.).
Surgical drains are utilized in spinal surgery to reduce the incidence of epidural hematomas (EDHs) and to facilitate optimal wound healing. Despite their widespread use, there is a paucity of data to support their utility. The goal of this systematic review and meta-analysis is to compare the effect of using drains versus no drains on postoperative outcomes in adult and pediatric patients undergoing posterior spinal fusions for deformity or degenerative conditions. The following outcomes were assessed: SSIs, EDHs, reoperations, transfusions, and length of stay (LOS). A systematic review of the literature in databases was conducted for all relevant literature. Exclusion criteria included single level decompressions, minimally invasive fusions, anterior-only approaches, and any surgical procedures performed for tumor, trauma, and osteomyelitis. Forest plots for Odds Ratios (ORs) and Mean Differences (MDs) were generated using random effects model. The search identified 2,210 titles, of which 11 studies were chosen for final analysis. 5 studies involved pediatric patients, while 6 included adult patients. A total of 3293 patients were analyzed-2,060 had a drain, and 1,233 had no drain. There were no statistically significant differences in the ORs of SSIs, EDHs, reoperations, and transfusions. LOS in adults was higher in the Drain group (MD 1.36 days 95% CI 0.25 - 2.47). This meta-analysis found no benefit in surgical drains in posterior spinal fusion in reducing the incidence of SSI, EDH, and reoperation. Drains may be associated with longer LOS in the adult population. PROSPERO registration number: CRD42023417315.
Increased vulnerability to seizures in aging has been well documented both clinically and in various models of aging in epilepsy. Seizures can exacerbate cognitive decline that is already prominent in aging. Senescent cells are thought to contribute to cognitive impairment in aging and clearing senescent cells with senolytic drugs improves cognitive function in animal models. It remains unclear whether senescent cells render the aged brain vulnerable to seizures. Here, we demonstrate that prophylactic senolytic treatment with Dasatinib and Quercetin (D&Q) reduced both seizure severity and mortality in aged C57BL/6J mice. We subjected the D&Q and VEH-treated aged mice to spatial memory testing before and after an acute seizure insult, Status Epilepticus [SE], which leads to epilepsy development. We found that senolytic therapy improved spatial memory before injury, however, spatial memory was not rescued after SE. Senescence-related proteins p16 and senescence-associated β-galactosidase were reduced in D&Q-treated aged mice. Our findings indicate that senescent cells increase seizure susceptibility in aging. Thus, prophylactically targeting senescent cells may prevent age-related seizure vulnerability.