anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
The present invention relates to the delivery of pharmaceuticals and other compounds to any wet tissue surface with a preferred application on mucosal surfaces. The device consists of a layered film comprising an adhesive layer, an erodible backing layer and an optional outer layer to improve mouth feel. Upon application, the device adheres to a wet tissue surface, and based on the composition of the erodible backing layer which is laminated to the adhesive layer, the device erodes uniformly and at a constant rate from the outside in. Due to this constant and unexpected uniform erosion characteristic, any compound present in the adhesive layer will be delivered to the treatment site at a rate dependent only on the erosion rate of the device. A pseudo zero order delivery rate is attained when an active is delivered on the oral mucosa and this rate can be regulated simply by changing the composition and thickness of the erodible backing layer. This backing layer is composed of both water soluble and water insoluble polymers, and by careful manipulation of the amount of each, the erosion rates can be regulated and subsequent drug delivery rates can be reproducibly altered. In addition, by keeping the device attached to the mucosa for extended and controlled periods of time, the active will pass through the intercellular pathway and provide more rapid and increased therapeutic blood levels. By changing only the backing layer of the device, peak blood levels can be altered.
This disclosure provides compositions and methods for controlling pain. In particular the disclosure provides a method for controlling pain comprising co-administration of an NGF antagonist and a TNFa antagonist. The NGF antagonist and the TNFa antagonist can be separate molecules or part of a multifunctional polypeptide, e.g., a multispecific binding molecule that comprises an NGF antagonist domain and a TNFa antagonist domain. This disclosure also provides multifunctional polypeptides, e.g., multispecific binding molecules, comprising an NGF antagonist domain, and a TNFa antagonist domain. The method provides improved pain control. Administration of an NGF antagonist and a TNFa antagonist as provided herein can control pain in the subject more effectively than an equivalent amount of the NGF antagonist or the TNFa antagonist administered alone.
All patient had long stimulation protocol and IVF/ICSI. After mock embryo transfer women with any degree of difficulty will receive Indomethacin 100Mg Suppository 1-2 hours before embryo transfer.
Any patient hospitalised in intensive care for a COVID-19 infection. The health emergency of this pandemic and the potential therapeutic action of HDL particles justify the choice of this population for study.
The investigational therapy in this trial, regulatory T cells (Tregs), is evaluating an alternative to traditional immunosuppressive therapies for the treatment of systemic lupus erythematosus (SLE, lupus). Too frequently, aggressive therapies are inadequate in the control of the disease and have potent side effects and complications. The collection and expansion of one's own T cells harnesses a naturally occurring regulatory mechanism to restore self-tolerance in people with lupus. Tregs are a specialized subset of T cells that function to control the immune response. Studies have shown that in active lupus, the numbers and function of Treg cells are significantly decreased, which contributes to an overactive immune system and an increase in disease activity. The hope is that these naturally occurring Treg cells can be used for the treatment of autoimmune diseases, including lupus.
Obese patients are known to have low levels of vitamin D metabolites. There is some evidence that vitamin D and/or dietary calcium may influence energy metabolism and body weight. We therefore perform a prospective controlled trial with 200 overweight (Body mass index 27-29.9 kg/m2) and obese subjects (Body mass index \>= 30 kg/m2) who are on a telemedically guided weight loss program. Subjects randomly receive a daily vitamin D supplement or a placebo for 1 year. Participants have to send their body weight data to the study office weekly. In addition, a nutritionist at the study office has to be contacted weekly to receive further support concerning the weight loss program. Dietary records have to be completed monthly. Clinical parameters and blood samples are collected at baseline, and after 6 and 12 months. It is the aim of the study to investigate the vitamin D effects on weight loss and body composition. In addition, possible vitamin D effects on clinical and selected biochemical parameters should be assessed. These parameters include heart rate, blood pressure, inflammation markers, and parameters of lipid and glucose metablolism.
Stable pharmaceutical prepns contg. E-series prostaglandins contain at least one thiol cpd and/or water-soluble high-molecular cpd and/or water-soluble desoxycholic acid salt and are prepd in freeze-dried form. E-series prostaglandins are used for controlling uterus contraction, as hypotensives, for treating peptic ulcers, for controlling fat metabolism and as bronchodilators, etc. The prepns can be stored at room temp. for long periods without decompsn they can be administered as aq. injection solns.
BACKGROUND: The mitochondrial dysfunction and oxidative stress imbalance caused by macrophage polarization play a role in the progression of COPD, with CDGSH iron-sulfur domain-containing protein 1 (CISD1) playing a key role. This study revealed the role and mechanism of CISD1 in smoke-induced macrophages.
METHODS: Using a pure cigarette smoke exposure-induced COPD mouse model, stimulation of Raw264.7 macrophages with cigarette smoke extract mimics the COPD environment. Knocking down CISD1 expression in macrophages and combining it with high-throughput sequencing to obtain subsequent differentially expressed genes and pathways. Macrophage polarization tendency under different treatments was determined using flow cytometry. Meanwhile, Mitosox, JC-1, DCFH-DA fluorescence intensity was measured to detect mitochondrial function and cellular oxidative stress levels. Western Blot technique was employed to validate autophagy (mitochondrial autophagy) pathway-related proteins. In addition, Elisa technique was used to measure inflammatory factors (IL-6, TNF-a) in the cell supernatant after co-culturing macrophages (Raw264.7) with epithelial cells (MLE12).
RESULTS: CISD1 is underexpressed in peripheral blood monocytes of COPD patients. Under in vitro conditions, we verified that cigarette smoke (smoke extract) indeed inhibits CISD1 expression in macrophages. Subsequently, we found that macrophages with knocked-down CISD1 tend to polarize towards M1 phenotype, and exhibit signs of mitochondrial dysfunction and oxidative stress imbalance. In addition, we observed significant activation of the autophagy pathway in CISD1-inhibited macrophages, with upregulation of LC3A/B and downregulation of p62 protein, as well as increased expression of mitochondrial autophagy-related proteins (PINK1, PARKN). Furthermore, co-culturing CISD1-knockdown macrophages (Raw264.7) with epithelial cells (MLE12) resulted in upregulation of inflammatory factors in the supernatant.
CONCLUSIONS: Smoke-induced reduction of CISD1 in macrophages promotes M1 polarization and mitochondrial dysfunction by activating the autophagy pathway, thereby promoting the occurrence and development of COPD.
UNLABELLED: Congenital central hypoventilation syndrome (CCHS), a rare disease caused by paired-like homeobox 2B variants, affects control of breathing. We report on a 21-month-old boy with CCHS caused by a novel nonpolyalanine repeat mutation, neuroblastoma, severe obstructive and central sleep apnea, and sleep-related hypoxemia without hypoventilation. At 10 months, due to persistent central sleep apnea during serial polysomnography, bilevel positive airway pressure therapy was initiated despite the absence of hypoventilation. Nonpolyalanine repeat mutations are associated with severe phenotypes requiring continuous assisted ventilation, Hirschsprung's disease, and neural crest tumors; however, our patient had a relatively milder respiratory phenotype requiring sleep-only assisted ventilation without tracheostomy. Although alveolar hypoventilation is the hallmark of CCHS, our patient lacked hypoventilation. Bilevel positive airway pressure could be considered in some infants with CCHS requiring sleep-only assisted ventilation for tracheostomy avoidance. Our case demonstrates the expanding phenotypic spectrum in CCHS and the importance of formulating an individualized care plan.
CITATION: Fain ME, Raghunandan S, Pencheva B, Leu RM, Kasi AS. Images: atypical presentation of congenital central hypoventilation syndrome in an infant with central and obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):478-481.
OBJECTIVE: The lactational period is associated with profound hyperphagia to accommodate the energy demands of nursing. These changes are important for the long-term metabolic health of the mother and children as altered feeding during lactation increases the risk of mothers and offspring developing metabolic disorders later in life. However, the specific behavioral mechanisms and neural circuitry mediating the hyperphagia of lactation are incompletely understood.
METHODS: Here, we utilized home cage feeding devices to characterize the dynamics of feeding behavior in lactating mice. A combination of pharmacological and behavioral assays were utilized to determine how lactation alters meal structure, circadian aspects of feeding, hedonic feeding, and sensitivity to hunger and satiety signals in lactating mice. Finally, we utilized chemogenetic, immunohistochemical, and in vivo imaging approaches to characterize the role of hypothalamic agouti-related peptide (AgRP) neurons in lactational-hyperphagia.
RESULTS: The lactational period is associated with increased meal size, altered circadian patterns of feeding, reduced sensitivity to gut-brain satiety signals, and enhanced sensitivity to negative energy balance. Hypothalamic AgRP neurons display increased sensitivity to negative energy balance and altered in vivo activity during the lactational state. Further, using in vivo imaging approaches we demonstrate that AgRP neurons are directly activated by lactation. Chemogenetic inhibition of AgRP neurons acutely reduces feeding in lactating mice, demonstrating an important role for these neurons in lactational-hyperphagia.
CONCLUSIONS: Together, these results show that lactation collectively alters multiple components of feeding behavior and position AgRP neurons as an important cellular substrate mediating the hyperphagia of lactation.
NIPPV is provided via binasal prongs. Ventilator settings:FiO2:21-40%,peak inspiratory pressure( PIP)：12-22cm H2O,positive and expiratory pressure(PEEP):5-7cm H2O,Rate:30-60 per minute to maintain SaO2 at 90-95%,The weaning process is left to the discretion of the attending physician,when FiO2: 25%,mean airway pressure (MAP):6cm H2O,R:30 per minute .
Participants randomly assigned to the event-driven TAF/FTC arm will be instructed to take one single tablet containing coformulated TAF/FTC (25/200mg) with or without food 2 to 24 hours before sexual intercourse followed by a second pill 24 hours after the first drug intake. In case of daily sexual intercourses, they will be instructed to take one pill per day until the last sexual intercourse and then a last pill 24 hours later.
A pilot study to develop the MTO-model including 10-15 patients, will be carried out and appropriate adjustments to the model will be made before starting the main study. Patients meeting the inclusion criteria will be invited to participate in the study and sent three questionnaires, MARS-5, EQ-5D-5L and BMQ-general, to fill in before starting the intervention. Baseline in this digital intervention is a medication interview with a clinical pharmacist. Based on the information from this interview, journal- and laboratory data, a comprehensive medication review will be conducted and a preliminary proposal discussed in a digital interdisciplinary meeting resulting in a final MTO-plan. The patients will be informed by their physician if any medication changes have been made and follow-up meetings with a pharmacist will take place 1-2,4 and 12 weeks after baseline and in addition of requested by the patients or if the pharmacist consider it necessary. In addition to the prescheduled meetings with the patient, the intervention includes repeated medical journal reviews every second week during the 12-weeks intervention. After the last follow-up at 12 weeks, the patient will be asked to fill in the three questionnaires; MARS-5, EQ-5D-5L and BMQ-general.
Tramadol HCl/acetaminophen is approved for short-term (five days or less) management of acute pain. The combination of tramadol HCl/acetaminophen provides a more rapid onset of action compared with tramadol HCl alone and a longer duration of action than acetaminophen alone. Therefore, the combination of tramadol HCl/acetaminophen may be effective for the treatment of acute musculoskeletal pain. The current study is a multicenter, randomized, double-blind, inpatient/outpatient, active-controlled, placebo-controlled, parallel-group study. Patients who are experiencing at least moderate acute musculoskeletal pain from an ankle sprain severe enough to require prescription medication will be enrolled. Patients will be randomized to receive either oral tramadol HCl/acetaminophen, hydrocodone bitartrate/acetaminophen or placebo. Patients will receive 2 capsules tramadol HCl/acetaminophen 37.5/325 milligrams or 1 capsule hydrocodone bitartrate/acetaminophen 7.5/650 milligrams + 1 capsule placebo or 2 capsules placebo. Patient may take 1 or 2 capsules up to 4 times daily as needed but no more than 8 capsules per day for 5 daysThe first dose of study medication will be given at the study site. Patients will complete a Pain Visual Analog Scale, Pain Relief Rating Scale and Pain Intensity Scale at 1, 2, 3 and 4 hours after the first dose of study medication. On Day 1, after the 4-hour evaluations, patients will be dispensed study medication for use throughout the rest of the study. Patients will also evaluate and record in a daily diary the pain intensity ratings and pain relief scores for Days 1-5 of the double-blind phase. At the final visit, patients will complete a Pain Intensity Scale and Pain Relief Rating Scale, an Activity Impairment Assessment and a Subject Overall Medication Assessment. At the first dose, patients are dispensed 2 capsules of study medication. Thereafter, patients may take 1 or 2 capsules of study medication orally up to 4 times per day, as needed for pain, but no more than 8 capsules per day. The objective of this study is to compare the pain-relieving effectiveness and safety of tramadol HCl/acetaminophen versus hydrocodone bitartrate/acetaminophen versus placebo for the treatment of acute musculoskeletal pain from an ankle sprain with a partial ligament tear.

2 capsules tramadol HCl/acetaminophen 37.5/325 milligrams or 1 capsule hydrocodone bitartrate/acetaminophen 7.5/650 milligrams + 1 capsule placebo or 2 capsules placebo; patient may take 1 or 2 capsules orally up to 4 times daily as needed but no more than 8 capsules per day for 5 days
The treatment guidelines for valvular heart disease indicate that surgical correction of primary mitral valve regurgitation (MR) is a Class I recommendation. Recent evidence indicates that valve replacement is at least as effective as repair in both primary and secondary MR patients. However, many patients are not referred for surgery as they are considered to be too high of a risk to undergo on-pump, open-heart procedures. Percutaneous aortic valve replacement has made treatment of stenosed aortic valves available to high-risk surgical patients who would have otherwise been medically managed. Percutaneous mitral valve (MV) replacement offers similar advantages. The feasibility of percutaneous MV replacement has been demonstrated in early feasibility studies. To meet this medical need, Caisson Interventional has developed a percutaneous delivery system for a bioprosthetic mitral valve. As with patients with aortic valve (AV) deficiencies, this device can be used to provide needed therapy to patients who might not otherwise receive treatment beyond medical therapy. This study will provide information on the safety and performance of this system.
Adrecizumab (HAM 8101) on top of standard of care. Adrecizumab (HAM8101) is a humanized IgG1 monoclonal antibody (mAb). 2 mg/kg body weight Adrecizumab diluted in up to 100 mL saline as single dose infusion.
BACKGROUND: Pericytes are a vital component of the blood-brain barrier, and their involvement in acute inflammation was recently suggested. However, it remains unclear whether pericytes contribute to hypothalamic chronic inflammation and energy metabolism in obesity. The present study investigated the impact of pericytes on the pathophysiology of obesity by focusing on platelet-derived growth factor (PDGF) signaling, which regulates pericyte functions.
METHODS: Tamoxifen-inducible systemic conditional PDGF receptor β knockout mice (Pdgfrb∆SYS-KO) and Calcium/calmodulin-dependent protein kinase type IIa (CaMKIIa)-positive neuron-specific PDGF receptor β knockout mice (Pdgfrb∆CaMKII-KO) were fed a high-fat diet, and metabolic phenotypes before and 3 to 4 weeks after dietary loading were examined. Intracellular energy metabolism and relevant signal transduction in lipopolysaccharide- and/or platelet-derived growth factor-BB (PDGF-BB)-stimulated human brain pericytes (HBPCs) were assessed by the Seahorse XFe24 Analyzer and Western blotting. The pericyte secretome in conditioned medium from HBPCs was studied using cytokine array kit, and its impact on polarization was examined in bone marrow-derived macrophages (BMDMs), which are microglia-like cells.
RESULTS: Energy consumption increased and body weight gain decreased after high-fat diet loading in Pdgfrb∆SYS-KO mice. Cellular oncogene fos (cFos) expression increased in proopiomelanocortin (POMC) neurons, whereas microglial numbers and inflammatory gene expression decreased in the hypothalamus of Pdgfrb∆SYS-KO mice. No significant changes were observed in Pdgfrb∆CaMKII-KO mice. In HBPCs, a co-stimulation with lipopolysaccharide and PDGF-BB shifted intracellular metabolism towards glycolysis, activated mitogen-activated protein kinase (MAPK), and modulated the secretome to the inflammatory phenotype. Consequently, the secretome showed an increase in various proinflammatory chemokines and growth factors including Epithelial-derived neutrophil-activating peptide 78 (C-X-C motif chemokine ligand (CXCL)5), Thymus and activation-regulated chemokine (C-C motif chemokine (CCL)17), Monocyte chemoattractant protein 1 (CCL2), and Growth-regulated oncogene α (CXCL1). Furthermore, conditioned medium from HBPCs stimulated the inflammatory priming of BMDMs, and this change was abolished by the C-X-C motif chemokine receptor (CXCR) inhibitor. Consistently, mRNA expression of CXCL5 was elevated by lipopolysaccharide and PDGF-BB treatment in HBPCs, and the expression was significantly lower in the hypothalamus of Pdgfrb∆SYS-KO mice than in control Pdgfrbflox/flox mice (FL) following 4 weeks of HFD feeding.
CONCLUSIONS: PDGF receptor β signaling in hypothalamic pericytes promotes polarization of macrophages by changing their secretome and contributes to the progression of obesity.
Method and system for determining glucose flux profiles in plasma during meals using continuous glucose sensors and insulin delivery. A database of plausible glucose flux profiles is encoded in dictionaries using sparse dictionary learning. A constrained Lasso minimization problem is formed that integrates a transport model for a patient with the dictionaries for estimating the glucose fluxes. Meal carbohydrates consumed by a patient is incorporated in the minimization problem through convex constraints. The estimated glucose fluxes resulting from solving the constrained Lasso minimization problem are glucose rate of appearance from the intestine, endogenous glucose production from the liver and insulin dependent glucose utilization. A method for determining patient carbohydrate to insulin ratio at the time of the meal by calculating the area under the curve of the estimated insulin dependent glucose utilization.
Usually, the fifth intercostal space was applied using the muscular-sparing technique. Fistula ligation, proximal pouch isolation and anastomosis were performed in turn.The fistula was then dissociated, ligated with 4-0 absorbable sutures, and divided. After identifying the proximal esophageal pouch with a nasogastatic tube, the proximal and distal blind ends were mobilized to prepare for anastomosis. Next, the tip of the blind ends was excised, and the anastomosis was completed with 5-0 absorbable sutures in an interrupted manner. A chest drain was placed alongside the anastomosis.
To investigate the feasibility of conventional (basketing + dusting) and Moses (pop-dusting) holmium lasers during flexible ureteroscopy (FURS) in the treatment of 2-3 cm renal calculi and to compare the efficiency and safety of the two methods, a total of 230 patients with 2-3 cm kidney stones who underwent FURS were randomly divided into the conventional group and the Moses group. The mode of lithotripsy in the conventional group was fragmentation and dusting. The mode of lithotripsy in the Moses group was dusting and pop-dusting. Clinical and perioperative variables and complications were compared between the two cohorts. Multivariate analyses of factors contributing to the stone-free rate (SFR) and operation time were performed. No statistically significant differences were found in the demographics, renal stone-related data, SFR, or complications between the cohorts. The laser energy was higher in the Moses cohort than in the conventional cohort (119.3 ± 15.2 vs. 92.8 ± 15.1 kJ; P < 0.001), and the operation time was shorter in the Moses cohort than in the conventional cohort (99.5 ± 18.9 vs. 105.3 ± 13.7 min; P = 0.009). When there was isolated stone, the operation time was shorter in the Moses cohort than in the conventional cohort (99.6 ± 17.5 vs. 111.4 ± 10.7 min; P < 0.001), while there was no significant difference between the two cohorts when there were multiple stones (99.5 ± 20 vs. 101.2 ± 14 min; P = 0.415). Multivariate analyses found that an increase in stone volume can decrease the SFR and prolong the operation time, and use of a Moses laser can shorten the operation time. Both holmium laser modes during FURS can effectively treat 2-3 cm renal calculi. The Moses mode is recommended as the first choice for the treatment of isolated 2-3 cm renal stones. When treating multiple stones, the efficiency of these two laser modalities is the same. TRIAL REGISTRATION: ChiCTR2200056091.
Control group will take conventional physiotherapy as in the literature. Diabetic individuals in routine takes aerobic exercise recommendation and resistive exercises. In our study control group will continue 12 sessions of resistive exercise program focused on upper extremity, also aerobic exercise recommendation.