anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
OBJECTIVE: Pharmacological activation of neuronal Kv7 channels by the antiepileptic drug retigabine (RTG; ezogabine) has been proven effective in treating partial epilepsy. However, RTG was withdrawn from the market due to the toxicity caused by its phenazinium dimer metabolites, leading to peripheral skin discoloration and retinal abnormalities. To address the undesirable metabolic properties of RTG and prevent the formation of phenazinium dimers, we made chemical modifications to RTG, resulting in a new RTG derivative, 1025c, N,N'-{4-[(4-fluorobenzyl) (prop-2-yn-1-yl)amino]-1,2-phenylene}bis(3,3-dimethylbutanamide).
METHODS: Whole-cell recordings were used to evaluate Kv7 channel openers. Site-directed mutagenesis and molecular docking were adopted to investigate the molecular mechanism underlying 1025c and Kv7.2 interactions. Mouse seizure models of maximal electroshock (MES), subcutaneous pentylenetetrazol (scPTZ), and PTZ-induced kindling were utilized to test compound antiepileptic activity.
RESULTS: The novel compound 1025c selectively activates whole-cell Kv7.2/7.3 currents in a concentration-dependent manner, with half-maximal effective concentration of .91 ± .17 μmol·L-1. The 1025c compound also causes a leftward shift in Kv7.2/7.3 current activation toward a more hyperpolarized membrane potential, with a shift of the half voltage of maximal activation (ΔV1/2) of -18.6 ± 3.0 mV. Intraperitoneal administration of 1025c demonstrates dose-dependent antiseizure activities in assays of MES, scPTZ, and PTZ-induced kindling models. Moreover, through site-directed mutagenesis combined with molecular docking, a key residue Trp236 has been identified as critical for 1025c-mediated activation of Kv7.2 channels. Photostability experiments further reveal that 1025c is more photostable than RTG and is unable to dimerize.
SIGNIFICANCE: Our findings demonstrate that 1025c exhibits potent and selective activation of neuronal Kv7 channels without being metabolized to phenazinium dimers, suggesting its developmental potential as an antiseizure agent for therapy.
Rivastigmine is well absorbed with absolute bioavailability of about 40% (3 mg dose). It shows linear pharmacokinetics up to 3 mg BID but is non-linear at higher doses. Doubling the dose from 3 to 6 mg BID results in a 3-fold increase in AUC. The elimination half-life is about 1.5 hours, with most elimination as metabolites via the urine.  
  
Absorption: Rivastigmine is rapidly and completely absorbed. Peak plasma concentrations are reached in approximately 1 hour. Absolute bioavailability after a 3 mg dose is about 36%. Administration of Rivastigmine Tartrate Capsules with food delays absorption (tmax) by 90 minutes, lowers Cmax by approximately 30% and increases AUC by approximately 30%.  
  
Distribution: Rivastigmine is widely distributed throughout the body with a volume of distribution in the range of 1.8 to 2.7 L/kg. Rivastigmine penetrates the blood brain barrier, reaching CSF peak concentrations in 1.4 to 2.6 hours. Mean AUC1-12hr ratio of CSF/plasma averaged 40 ± 0.5% following 1 to 6 mg BID doses.  
  
Rivastigmine is about 40% bound to plasma proteins at concentrations of 1 to 400 ng/mL, which cover the therapeutic concentration range. Rivastigmine distributes equally between blood and plasma with a blood-to-plasma partition ratio of 0.9 at concentrations ranging from 1 to 400 ng/mL.  
  
Metabolism: Rivastigmine is rapidly and extensively metabolized, primarily via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. Based on evidence from in vitro and animal studies, the major cytochrome P450 isozymes are minimally involved in rivastigmine metabolism. Consistent with these observations is the finding that no drug interactions related to cytochrome P450 have been observed in humans [see Drug-Drug Interactions].  
  
Elimination: The major pathway of elimination is via the kidneys. Following administration of 14C-rivastigmine to 6 healthy volunteers total recovery of radioactivity over 120 hours was 97% in urine and 0.4% in feces. No parent drug was detected in urine. The sulfate conjugate of the decarbamylated metabolite is the major component excreted in urine and represents 40% of the dose. Mean oral clearance of rivastigmine is 1.8 ± 0.6 L/min after 6 mg BID.
The present invention discloses a medicine for hemostasis, blood stasis removal and coaptation, which is prepared from 17 kinds of medicines, such as frankincense, rhubarb, dragon's blood, angelica, borax, myrrh, ground beetle, drynaria, cinnabar, safflower, native copper, catechu, dipsacus root, notoginseng, borneol, scorpion, Chinese ephedra, etc. The medicines are ground into powders after being mixed. The medicine is externally applied while orally taken by patients. The medicine can treat traumatic injuries, such as incised wounds, gunshot wounds, contusion, stremma, etc., fractures and old fractures, and especially have bone regeneration effect on old fractures. The medicine has the functions of hemostasis, acesodyne, blood activation, blood stasis removal, channels and collaterals dredging, fracture setting, and cold and dampness elimination. The effective rate and the cure rate of the medicine for treating traumatic injuries respectively reach 100% and 99%; the effective rate and the cure rate of the medicine for the coaptation for fracture patients respectively reach 99% and 98%, without toxic or side effect.
Psychiatric Adverse Reactions

Scopolamine has been reported to exacerbate psychosis. Other psychiatric reactions have also been reported, including acute toxic psychosis, agitation, speech disorder, hallucinations, paranoia, and delusions [see Adverse Reactions (6.2)]. Monitor patients for new or worsening psychiatric symptoms during treatment with TRANSDERM SCŌP. Also, monitor patients for new or worsening psychiatric symptoms during concomitant treatment with other drugs that are associated with similar psychiatric effects [see Drug Interactions (7.1)]. In cases of psychiatric reactions occurring TRANSDERM SCŌP should be removed at once. If, despite this, the symptoms persist in a severe form, instruct patients to seek medical attention.

Seizures

Seizures and seizure-like activity have been reported in patients receiving scopolamine. Weigh this potential risk against the benefits before prescribing TRANSDERM SCŌP to patients with a history of seizures, including those receiving anti-epileptic medication or who have risk factors that can lower the seizure threshold. 

Cognitive Adverse Reactions

Scopolamine can cause drowsiness, disorientation, and confusion. Discontinue TRANSDERM SCŌP if signs or symptoms of cognitive impairment develop. If, despite this, the symptoms persist in a severe form, instruct patients to seek medical attention. Elderly and pediatric patients may be more sensitive to the neurological and psychiatric effects of TRANSDERM SCŌP. Consider more frequent monitoring during treatment with TRANSDERM SCŌP in elderly patients [see Use in Specific Populations (8.5)]. TRANSDERM SCŌP is not approved for use in pediatric patients [see Use in Specific Populations (8.4)].

Hazardous Activities

TRANSDERM SCŌP may impair the mental and/or physical abilities required for the performance of hazardous tasks such as driving a motor vehicle, operating machinery or participating in underwater sports. Concomitant use of other drugs that cause central nervous system (CNS) adverse reactions (e.g., alcohol, sedatives, hypnotics, opiates, and anxiolytics) or have anticholinergic properties (e.g., other belladonna alkaloids, sedating antihistamines, meclizine, tricyclic antidepressants, and muscle relaxants) may increase this effect [see Drug Interactions (7.1)]. Inform patients not to operate motor vehicles or other dangerous machinery or participate in underwater sports until they are reasonably certain that TRANSDERM SCŌP does not affect them adversely.
The invention provides novel methods and compositions for the treatment of immune system-mediated arthritis, including rheumatoid arthritis. The subject compositions comprise one or more different types of collagen or collagen derivatives and a mucosa binding structure. Specific combinations of collagen and/or collagen derivatives may be used to treat specific types of arthritis. The collagen and/or collagen derivatives used in the subject compositions may be either obtained from natural sources or produced by recombinant genetic engineering techniques by chemical modification. Another aspect of the invention is to provide methods for treating various types of arthritis by administering an effective amount of the subject collagen-containing compositions. The methods of the invention involve the oral administration of a collagen or collagens found in a specific tissue, so as to induce the suppression (immunological tolerance) of inflammation against the tissue from which the collagen is found to occur in nature. The methods of the invention include the administration of the subject collagen and/or collagen derivative containing compositions into the intestines so as to induce immune tolerance, e.g., oral administration.
The study team will recruit 60 teens and young adults with persistent asthma who are at high risk for future exacerbation from the University of North Carolina at Chapel Hill (UNC) Children's Allergy and Asthma Center in Raleigh, NC. Participants will complete 13 study visits: an initial in-person visit (the study team will make every attempt to coordinate this visit with a scheduled clinic visit) and 12 monthly virtual follow up visits. Participants will be asked to use an at home spirometer once daily in the evening and will also complete an electronic asthma survey each night. Participants will also be provided with a sensor that tracks their rescue medication use throughout the study. Participants will undergo collection of nasal epithelial lining fluid (NELF) at the baseline visit. During the 12 months of study, participants will self-collect NELF samples if certain prespecified criteria for asthma exacerbation are met. Samples will be analyzed for IL-1β, interleukin receptor antagonist (IL-1RA) and other mediators associated with acute asthma exacerbation. Virtual follow up visits using a video platform will occur monthly for 12 months. Participants will self-report healthcare utilization and prescription for systemic corticosteroids. Spirometry and symptom survey data will be matched to subject-reported asthma exacerbations. The study design is adapted to minimize in-person visits, using web-based platforms for virtual visits and self-collection of samples to prioritize safety during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic.
Subjects will receive single oral dose of 400 milligram (mg) un-labeled GW842166X. After 2-5 hours subjects will receive \[carbonyl-\^11C\]GW842166.
BACKGROUND: Chronic shoulder pain is a common musculoskeletal problem associated with unreleased pain and functional dysfunction that can evolve into central sensitization. Some forms of manual therapy may exacerbate pain and central sensitization. This study investigated the impact of joint position sense therapy (JPST), a moderate joint proprioception training technique, on central sensitization, shoulder functional dysfunction, and pain in patients with chronic shoulder pain compared with more intense exercises or aggressive manual therapies.
METHODS: We assessed the pressure pain threshold (PPT) in 30 patients with and 30 patients without chronic shoulder pain. The assessment focused on 4 muscle sites: deltoid, upper trapezius, brachioradialis, and tibialis anterior. Thirty patients with chronic shoulder pain were randomly divided into the JPST and control groups. The JPST group underwent additional shoulder joint position-sense training. The efficiency outcomes were the disabilities of the arm, shoulder, and hand questionnaire, visual analog scale (VAS), and PPT, evaluated at baseline and after the intervention.
RESULTS: Significant differences were observed in the PPT values at the brachioradialis (P < .05), deltoid (P < .01), and trapezius (P < .001) among the non-chronic and chronic groups, but not in the tibialis anterior muscle (P > .05). Although both control and JPST interventions effectively improved the disabilities of the arm, shoulder, and hand questionnaire score, pain intensity, and PPT values in the upper limb, the outcomes in the JPST group were significantly different from those in the control group.
CONCLUSIONS: Generalized hyperalgesia changes limited to the upper limbs were observed in patients with chronic shoulder pain. JPST has beneficial effects on pain control and functional dysfunction in patients with chronic shoulder pain.
1384267 Foamed polymeric cleansing pads BRISTOL MYERS CO 24 July 1972 [28 July 1971] 34483/72 Heading C5D [Also in Division C3] Cleansing compositions consist of a detergent within a polymeric foamed structure, e.g. an applicator pad, which is made from an oil-inwater emulsion comprising a continuous phase of water containing a foam-stabilizing agent and dispersed in the water, as a discontinuous phase, a solution of a film-forming synthetic polymer in a liquid propellant, i.e. a volatile organic compound boiling below 45‹ F. at atmospheric pressure and retained in the liquid phase at super-atmospheric pressure, and dispersed or dissolved in the emulsion a detergent which is deposited with the water phase in the cells and walls of the foamed structure produced when the propellant volatilizes and which can be removed from the cells of the structure. The emulsion can be formed into a foamed structure by expelling it from a closed container, e.g. an aerosol container, and volatilizing the propellant at atmospheric pressure and temperature so as to foam the synthetic polymer and form a foamed structure.  In Examples 1-11 cleansing pads were made by expelling from aerosol cans oil-in-water emulsions containing as the aqueous phase water with triethanolamine lauryl sulphate or polyoxyethylene lauryl ether and optionally isopropanol or ethyl alcohol and as the oil phase a solution of polymer (vinyl toluene-acrylate copolymer, polyvinyl acetate, cellulose acetate butyrate or polyisobutylmethacrylate and optionally oleyl alcohol) in propellant (trichlorofluoromethane dichlorodifluoromethane, 1- chloro-1,1-difluoroethane and/or 1,2-dichlorotetrafluoroethane).
Age-related macular degeneration (AMD), characterized by macular retinal degeneration, poses a significant health concern due to the lack of effective treatments for prevalent dry AMD. The progression of AMD is closely linked to reactive oxygen species and Fas signaling, emphasizing the need for targeted interventions. In this study, we utilized a NaIO3-induced retinal degeneration mouse model to assess the efficacy of Fas-blocking peptide (FBP). Intravitreal administration of FBP successfully suppressed Fas-mediated inflammation and apoptosis, effectively arresting AMD progression in mice. We developed a 6R-conjugated FBP (6R-FBP) for eye drop administration. 6R-FBP, administered as an eye drop, reached the retinal region, attenuating degeneration by modulating the expression of inflammatory cytokines and blocking Fas-mediated apoptosis in rodent and rabbit NaIO3-induced retinal degeneration models to address practical concerns. Intravitreal FBP and 6R-FBP eye drops effectively reduced retinal degeneration and improved retinal thickness in rodent and rabbit models. This study highlights the therapeutic potential of FBP, particularly 6R-FBP as an eye drop, in inhibiting Fas-mediated cell signaling and protecting against retinal cell death and inflammation in dry AMD. Future investigations should explore the translational prospects of this approach in primates with eye structures comparable to those of humans.
Premenopausal women with endometriosis-related CPP scheduled for laparoscopic surgery to our Academic Department of Gynecology will be consecutively enrolled. Subjects with hystologically confirmed endometriosis at laparoscopy (stage I-IV of the American Society Reproductive Medicine), a subjective severity of pelvic pain by using a visual analogue scale (VAS 1-100) of at least 70, and without immediate desire of pregnancy will be enrolled.

Briefly, all patients will undergo conservative laparoscopic surgery for endometriosis. Thereafter, a low-dose monophasic OC containing 2.0 mg clormadinone acetate plus 0.03 mg ethinil-estradiol (Belara®, Grunenthal, Milan, Italy) will be administered. Patients from the experimental group will be treated with a continuous regimen, while patients from the control group will receive the OC with a cyclic regimen consisting of 21 days of active pills with 7 days of placebo. The drug and the placebo will be similar and will be labelled according to the subject number. For the overall study-period, operators and patients will be blind to the treatment allocation.
This study will be enrolled using a 3+3 model. Patients will receive one dose of neoadjuvant durvalumab 1500 mg approximately 3-6 weeks prior to standard of care surgery. It will be given concurrently with the first dose of radiation (RT). The starting RT dose level will be given as 6 Gy for 2 fractions (12 Gy total) every other day over approximately one week to sites of gross disease (Table 1) only to minimize exposure to normal tissue. If toxicity develops and surgery is delayed by more than 8 weeks (qualifying as a DLT), the radiation dose will be dropped per protocol for the next set of patients. If this dose is tolerated, the dose will be increased to 6 Gy for 3 fractions (18 Gy total) for the next 3 patients. Patients will proceed to surgical resection approximately 3-6 weeks after radiation as recommended by the ENT surgeon.
In order to diagnose human health as precisely as possible, it is necessary to measure and analyze as much as possible the human and his environmental factors. With increasing environmental factors and the increasing amount of data, it is difficult for medical professionals to choose the factors necessary for measurement, to properly configure the measurement, analysis, and diagnostic equipment. This invention is a new measurement, analysis and diagnostic equipment used in a medical field for measuring and analyzing cardiac activity. Measured parameters of human and his environmental factors are synchronized in accordance with cardiac activity parameters (Recg or RRI). The measurement, analysis and diagnostic equipment is composed of at least a central processing unit and sensors. Unlike the related art, sensors process the measured data and transmit only a significant feature or sequence over time of features to the central unit, i. e. provides already processed data. In this way, technical resources of the central unit can be used to process and deliver the data in real time, to perform an advanced analysis, to include a large amount of the measured parameters.
All women with fetuses having either severe LUTO with intrauterine renal failure or bilateral renal agenesis that meet the inclusion criteria will be invited to participate in this study. For those patients, the actual standard of care is expectant prenatal management or termination of pregnancy (\<22 weeks according to law). This study will offer serial amnioinfusions for patients with LUTO or bilateral renal agenesis. Due to the rarity and complexity of these cases, the investigators expect to enroll a maximum of 5 women with affected fetuses per year. After two years (approximately 10 cases), a review of the data will be completed including all outcomes to determine whether to continue towards the original goal of treating 40 patients (20 mothers with affected fetuses) or to close the study,.

All procedures are anticipated to take place in the Family Birth Center at Mayo Clinic, Rochester. Serial ultrasound-guided amnioinfusion procedures will be performed on fetuses having severe LUTO or bilateral renal agenesis that are diagnosed between 18 0/7-25 6/7 weeks. This procedure will be performed in a sterile fashion within the operating room using the same technique that is routinely used to perform the ultrasound-guided amnioinfusion. Once consented, weekly ultrasound monitoring will be conducted and if the amniotic fluid index (AFI) is determined to be \<2 cm, amnioinfusion will proceed. Prior to each infusion, 5mLs of amniotic fluid will be collected to study surrogate markers of lung function (research only). Using a 22-gauge needle, warm sterile lactated ringer solution will be infused into the amniotic cavity until the AFI is equal to 8 cm. Some studies have demonstrated that the composition of the amniotic fluid during second and third trimester is closer to the lactated ringer solution. This procedure will be continued weekly until the fetus reaches 34 weeks, after which only monitoring will occur. If preterm premature rupture of the membranes (PPROM) occurs prior to 34 weeks, no further amnioinfusion procedures will be performed. Patients with PPROM will be managed according to the standardized clinical management. The anticipated length of stay in the hospital after each infusion is approximately 2 days if no uterine contractions are observed.

The prenatal care, delivery and postnatal management of the infant will be conducted according to the standardized clinical care. Delivery will be scheduled at the Mayo Clinic Family Birth Center and the infants will be followed for 24 months by the multi-specialty team as part of the standard clinical management including follow-up with neonatologist (NICU team), pediatric nephrology and transplant team according to the clinical protocol for postnatal renal replacement therapy and transplant. Neurodevelopment of the children will assessed using a combination of clinical examination and the Bayley Scale of Infant Development during the first 24 months of life.
Bowel strictures are well recognized as one of the most severe complications in Crohn's disease, with variable impacts on the prognosis and often needing surgical or endoscopic treatment. Distinguishing inflammatory strictures from fibrotic ones is of primary importance due to the different therapeutic approaches required. Indeed, to better understand the pathogenesis of fibrosis, it is crucial to investigate molecular processes involving genetic factors, cytokines, alteration of the intestinal barrier, and epithelial and endothelial damage, leading to an increase in extracellular matrix synthesis, which ultimately ends in fibrosis. In such a complex mechanism, the gut microbiota also seems to play a role. A better comprehension of molecular processes underlying bowel fibrosis, in addition to radiological and histopathological findings, has led to the identification of high-risk patients for personalized follow-up and testing of new therapies, primarily in preclinical models, targeting specific pathways involving Transforming Growth Factor-β, interleukins, extracellular matrix balance, and gut microbiota. Our review aims to summarize current evidence about molecular factors involved in intestinal fibrosis' pathogenesis, paving the way for potential diagnostic biomarkers or anti-fibrotic treatments for stricturing Crohn's disease.