anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In the project proposed here our main aim is to shift pain modulation towards anti-nociception as a novel approach to pain prevention and treatment. Our first hypothesis is that individual's modulation profile, when not anti-nociceptive, can be pharmacologically shifted into being anti-nociceptive. We assert (the first hypothesis) that such shift can be optimized by coupling the drug's mode of action with the individual's pain modulation profile; based on limited available data, it is suggested that less efficient inhibitory pain modulation will be modified best by serotonin-norepinephrine reuptake inhibitors (SNRIs), whereas enhanced facilitatory modulation will be modified best by Ca++ channel ligands. Pain modulation will be assessed by psychophysical tools, and will include dynamic tests of pain modulation. The conditioned pain modulation (CPM) test protocol will be used for assessing pain inhibition, and the temporal summation (TS) test protocol will be used for assessment of pain facilitation. Our second hypothesis is that SNRIs will be most efficacious in shifting individuals into being antinociceptive if these individuals had lower activation of the anterior brain pain network in the CPM test paradigm. In turn, Ca++ channel ligands will be most efficacious for individuals showing enhanced activation of the posterior pain network sites in response to the TS test protocol. Our third hypothesis is that an anti-nociceptive pain modulation profile protects individuals from acquiring pain. The model we chose for this study is surgery for coronary artery bypass grafting (CABG). Individuals scheduled for surgery, who are pain free, will be assigned to 3 arms - (1) duloxetine (DUL) (SNRI), (2) pregabalin (PGB) (Ca++ channel ligand) and (3) placebo. Drugs will be taken for 48 hours prior to surgery in a double-blind non cross-over parallel design. Pain modulation will be assessed before treatment, 2-4 hours prior to surgery and at its end, 6 weeks before surgery. Post operative acute and chronic pain will be assessed up to 2 month after surgery.
The invention relates to chemical-pharmaceutical industry and concerns creation of novel suppositories, which can be used for treatment of gynecological inflammatory diseases, as well as genital viral infections (herpes, papillomavirus, cytomegalovirus). The task of the claimed invention is to create a medication, possessing higher level of anti-inflammatory and antibacterial activity. The set task is solved by that the medication for treatment of gynecological diseases is based on cocoa oil and propolis, where in accordance with the invention, the medication additionally contains thick liquorice extract with moisture content of not more than 25%, sea buckthorn oil, tea tree oil, milk thistle oil, wheat oil and 5 drops of iodine. Essence of the claimed invention is characterized by that the claimed composition possesses properties of antiseptic of natural origin of immunostimulating, anti-inflammatory, antimicrobial and antiviral action. Due to natural antibiotic and antiseptic properties it does not injure the healthy tissue, does not irritate especially sensitive skin regions, stimulates the immune system and can help in treatment of a number of diseases. Absence of side effects is an important advantage of the composition.
BACKGROUND: Hypertension and diabetes are major risk factors for cardiovascular diseases, stroke, and chronic kidney disease (CKD). Disparities in hypertension control persist among Black and Hispanic adults and persons living in poverty in the United States. The "LINKED-HEARTS Program" (a Cardiometabolic Health Program LINKED with Community Health WorkErs and Mobile HeAlth TelemonitoRing To reduce Health DisparitieS"), is a multi-level intervention that includes home blood pressure (BP) monitoring (HBPM), blood glucose telemonitoring, and team-based care. This study aims to examine the effect of the LINKED-HEARTS Program intervention in improving BP control compared to enhanced usual care (EUC) and to evaluate the reach, adoption, sustainability, and cost-effectiveness of the program.
METHODS: Using a hybrid type I effectiveness-implementation design, 428 adults with uncontrolled hypertension (systolic BP ≥ 140 mm Hg) and diabetes or CKD will be recruited from 18 primary care practices, including community health centers, in Maryland. Using a cluster-randomized trial design, practices are randomly assigned to the LINKED-HEARTS intervention arm or EUC arm. Participants in the LINKED-HEARTS intervention arm receive training on HBPM, BP and glucose telemonitoring, and community health worker and pharmacist telehealth visits on lifestyle modification and medication management over 12 months. The primary outcome is the proportion of participants with controlled BP (<140/90 mm Hg) at 12 months.
CONCLUSIONS: The study tests a multi-level intervention to control multiple chronic diseases. Findings from the study may be leveraged to reduce disparities in the management and control of chronic diseases and make primary care more responsive to the needs of underserved populations.
TRIAL REGISTRATION: ClinicalTrials.gov. Identifier: NCT05321368.
With the substantial increase in the overuse of glucocorticoids (GCs) in clinical medicine, the prevalence of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) continues to rise in recent years. However, the optimal treatment for GC-ONFH remains elusive. Rotating magnetic field (RMF), considered as a non-invasive, safe and effective approach, has been proved to have multiple beneficial biological effects including improving bone diseases. To verify the effects of RMF on GC-ONFH, a lipopolysaccharide (LPS) and methylprednisolone (MPS)-induced invivo rat model, and an MPS-induced invitro cell model have been employed. The results demonstrate that RMF alleviated bone mineral loss and femoral head collapse in GC-ONFH rats. Meanwhile, RMF reduced serum lipid levels, attenuated cystic lesions, raised the expression of anti-apoptotic proteins and osteoprotegerin (OPG), while suppressed the expression of pro-apoptotic proteins and nuclear factor receptor activator-κB (RANK) in GC-ONFH rats. Besides, RMF also facilitated the generation of ALP, attenuated apoptosis and inhibits the expression of pro-apoptotic proteins, facilitated the expression of OPG, and inhibited the expression of RANK in MPS-stimulated MC3T3-E1 cells. Thus, this study indicates that RMF can improve GC-ONFH in rat and cell models, suggesting that RMF have the potential in the treatment of clinical GC-ONFH.
(1) Background: Valproic acid (VPA) is one of the frequently prescribed antiepileptic drugs and is generally considered well tolerated. However, VPA neurologic adverse effects in the absence of liver failure are fairly common, suggesting that in the mechanism for the development of VPA-induced encephalopathy, much more is involved than merely the exposure to hyperammonemia (HA) caused by liver insufficiency to perform detoxification. Taking into account the importance of the relationship between an impaired brain energy metabolism and elevated ammonia production, and based on the ability of VPA to interfere with neuronal oxidative pathways, the current study intended to investigate a potential regional ammoniagenic effect of VPA on rats' brains by determining activities of the enzymes responsible for ammonia production and neutralization. (2) Methods: Rats received a single intraperitoneal injection of VPA (50, 100, 250, 500 mg/kg). Plasma, the neocortex, the cerebellum, and the hippocampus were collected at 30 min after injection. The levels of ammonia, urea, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in blood plasma. The activities of glutaminase and glutamate dehydrogenase (GDH) in mitochondria and the activities of AMP deaminase (AMPD), adenosine deaminase (ADA), and glutamine synthetase (GS) in cytosolic fractions isolated from rat brain regions were measured. Ammonia, ALT, and AST values were determined in the mitochondrial and cytosolic fractions. (3) Results: Multi-dose VPA treatment did not significantly affect the plasma levels of ammonia and urea or the ALT and AST liver enzymes. Significant dose-independent increases in the accumulation of ammonia were found only in the cytosol from the cerebellum and there was a strong correlation between the ammonia level and the ADA activity in this brain structure. A significant decrease in the AMPD and AST activities was observed, while the ALT activity was unaffected. Only the highest VPA dose (500 mg/kg) was associated with significantly less activity of GS compared to the control in all studied brain structures. In the mitochondria of all studied brain structures, VPA caused a dose-independent increases in ammonia levels, a high concentration of which was strongly and positively correlated with the increased GDH and ALT activity, while glutaminase activity remained unchanged, and AST activity significantly decreased compared to the control in all studied brain structures. (4) Conclusions: This study highlights the rat brain region-specific ammoniagenic effects of VPA, which may manifest themselves in the absence of hyperammonemia. Further research should analyze how the responsiveness of the different brain regions may vary in VPA-treated animals that exhibit compromised energy metabolism, leading to increased ammoniagenesis.
FIELD: medicine, ophthalmology. SUBSTANCE: three variants of improved ophthalmological composition are described which are especially useful for decreasing glaucoma- associated intraocular pressure. Compositions contain active substance out of prostaglandins' class, for example, isopropyl ether 13,14,dihydro-15-keto-20-ethyl-PGF 2 α, in combination with certain nonionogenic surface-active substances, conservants and nonionic tonicity-regulating agents. New modified compositions based upon prostaglandins are manufactured by a simple method and possess balanced efficiencies in decreasing intraocular pressure and conservation, tolerance for an eye and storage duration. EFFECT: higher efficiency. 23 cl, 14 ex, 3 tbl
PROBLEM TO BE SOLVED: To provide a combination of MEK inhibitor and Aurora-A kinase selective inhibitor.SOLUTION: The present invention relates to a method of treating proliferative disorders. In particular, the present invention provides a method of treating proliferative disorders by administering a combination of MEK inhibitor and Aurora-A kinase selective inhibitor. The present invention provides a novel combination therapy for treating proliferative disorders. In particular the present invention provides a method of treating patients suffering from proliferative disorders, including the administration of a combination of MEK inhibitor and Aurora-A kinase selective inhibitor, the amount of each inhibitor being therapeutically effective when used in combination. The present invention also provides MEK inhibitor combined with Aurora-A kinase selective inhibitor for use in the production of drugs for treating proliferative disorders with the amount of each inhibitor being therapeutically effective when used in combination. The present invention also provides a pharmaceutical composition comprising MEK inhibitor combined with Aurora-A kinase selective inhibitor and a kit.SELECTED DRAWING: None
The invention relates to the discovery and characterization of several genes and the polypeptides they encode: thymotaxin (Tango-45), Tango-63d, Tango-63e, Tango-67, and huchordin (Tango-66). Thymotaxin is a new member of the C—C family of chemokines. Tango-63d and Tango-63e are two novel polypeptides within the tumor necrosis factor (TNF) receptor superfamily. Tango-67 is related to a number of growth factors. particularly members of the connective tissue growth factor family. Huchordin is related to chordin, a known protein that is involved in the induction of twinned axes, can completely rescue axial development in ventralized embryos, is a potent dorsalizing factor, and plays a crucial role in regulating cell-cell interactions in the organizing centers of head, trunk, and tail development. The invention encompasses nucleic acid molecules encoding nucleic acids and polypeptides of the invention, or mutant forms thereof that encode dysfunctional receptor polypeptides, vectors containing these nucleic acid molecules, cells harboring recombinant DNA molecules encoding nucleic acids or polypeptides of the invention, or mutant forms thereof, host fusion proteins that include functional or dysfunctional polypeptides of the invention, transgenic animals that express nucleic acids or polypeptides of the invention, screening methods and therapeutic methods employing the nucleic acid molecules and polypeptides described above, substantially purified nucleic acids and polypeptides of the invention, and therapeutic compositions containing these nucleic acid molecules and polypeptides.
A composition for conditioning the skin and retarding the rate of moisture loss therefrom comprises substantially 50 to 70% by weight of a mixture and triglycerides comprising substantially 45 to 65% by weight of saturated triglycerides of higher fatty acids and substantially 55 to 35% by weight of unsaturated triglycerides of higher fatty acids, said acids having 12 to 18 carbon atoms, substantially 15 to 30% by weight of wax comprising the esters of higher fatty acids having 10 to 32 carbon atoms with higher aliphatic monohydric alcohols having 14 to 32 carbon atoms and substantially 10 to 25% by weight of high molecular weight hydrocarbons containing from 10 to 60 carbon atoms, substantially 30 to 70% by weight of said hydrocarbons consisting of squalene, and if desired, some sterols, sterol esters or mixtures thereof. Specified saturated triglycerides are those formed from myristic, palmitic and stearic acid and unsaturated triglycerides are formed from acids such as palmitoleic, oleic, linoleic and linoleric acid.  Natural sources of the mixtures of saturated and unsaturated triglycerides are cocoa butter, lard, palm oil, beef tallow, mutton tallow, chinese tallow, hydrogenated cotton seed oil, hydrogenated coconut oil, sperm body oil or sperm head oil. Specified saturated waxes are cetyl palmitate, stearyl stearate, myristyl behenate, myricyl cerotate, arachyl melissate, ceryl cerotate, ceryl palmitate or pisangceryl carnaubate. Unsaturated waxes are oleyl oleate, palmitoleyl palmitate, oleyl cerotate or myristyl oleate.  Natural wax sources are beeswax, spermaceti wax, sperm oil, carnauba wax, chinese insect wax or banana wax. Hydrocarbons used are petrolatum and mineral oil.  Specified sterols are cholesterol, dihydrocholesterol, 7 - oxocholesterol, dihydrolanosterol, cholest - zen - 3 - ol, cholestan - 3,5,6 - triol, agnosterol, lanosterol or esters thereof.  The compositions may also include cosmetic carriers such as glycerin, stearic or oleic acid, ethylene glycol monostearate, polyethylene glycol, diethylene glycol monolaurate, sorbitol, sorbitan sesquioleate, lanolin alcohols, sodium lauryl sulphate, white wax, paraffin wax, candella wax, ozokerite wax, castor oil, perfumes, colouring agents, preservatives, germicides, fungicides or ultra-violet screening compounds. Specified forms are ointments, lotions, oils, creams, sprays, lipsticks or pastes.
Under recuiting 480 patients come from 5 hospitals in China.Eligible patients will be randomly assigned into 2 groups: treatment group and control group. The treatment group will receive "Huo Xue San Feng" acupuncture combining 1 antihypertensive medication on the routine ischemic stroke treatments' basis. The control group will receive 1 antihypertensive medication and basic treatments for ischemic stroke. "Huo Xue San Feng" acupuncture will be given six sessions weekly for the first 6 weeks and three times weekly for the next 6 weeks. A 9-month follow-up will thereafter be conducted. Antihypertensive medications will be adjusted based on BP levels.
The N6-methyladenosine (m6A) modification of RNA is an emerging epigenetic regulatory mechanism that has been shown to participate in various pathophysiological processes. However, its involvement in modulating neuropathic pain is still poorly understood. In this study, we elucidate a functional role of the m6A demethylase alkylation repair homolog 5 (ALKBH5) in modulating trigeminal-mediated neuropathic pain. Peripheral nerve injury selectively upregulated the expression level of ALKBH5 in the injured trigeminal ganglion (TG) of rats. Blocking this upregulation in injured TGs alleviated trigeminal neuropathic pain, while mimicking the upregulation of ALKBH5 in intact TG neurons sufficiently induced pain-related behaviors. Mechanistically, histone deacetylase 11 downregulation induced by nerve injury increases histone H3 lysine 27 acetylation (H3K27ac), facilitating the binding of the transcription factor forkhead box protein D3 (FOXD3) to the Alkbh5 promoter and promoting Alkbh5 transcription. The increased ALKBH5 erases m6A sites in Htr3a messenger RNA (mRNA), resulting in an inability of YT521-B homology domain 2 (YTHDF2) to bind to Htr3a mRNA, thus causing an increase in 5-HT3A protein expression and 5-HT3 channel currents. Conversely, blocking the increased expression of ALKBH5 in the injured TG destabilizes nerve injury-induced 5-HT3A upregulation and reverses mechanical allodynia, and the effect can be blocked by 5-HT3A knockdown. Together, FOXD3-mediated transactivation of ALKBH5 promotes neuropathic pain through m6A-dependent stabilization of Htr3a mRNA in TG neurons. This mechanistic understanding may advance the discovery of new therapeutic targets for neuropathic pain management.
PCT No. PCT/US92/06776 Sec. 371 Date Feb. 24, 1994 Sec. 102(e) Date Feb. 24, 1994 PCT Filed Aug. 19, 1992 PCT Pub. No. WO93/03724 PCT Pub. Date Mar. 4, 1993The present invention provides a new composition, food product and uses for a known compound. More particularly, the present invention provides a new pharmaceutical composition containing 3-guanidinopropionic acid and a method of using 3-guanidinopropionic acid to prevent or treat obesity in non-insulin dependent diabetic (NIDDM) patients that is caused by treatment with anti-diabetic drugs, such as an insulin sensitizing drug or an insulin secretion stimulating drug. Examples of insulin sensitizing drugs are pioglitazone and pioglitazone hydrochloride. Examples of insulin secretion stimulating drugs are glyburide and glimepiride. The present invention also provides a new food product containing 3-guanidinopropionic acid and a method of using 3-guanidinopropionic acid to increase endurance, stamina and exercise capacity.
Intervention is administrated with an inspiratory muscle trainer (IMT). High intensity group: 15 cycles, 1 minute each one, 40% MIP with IMT. 1 minute to rest between cycles.
Abstract of the Disclosure Pharmaceutical composition for treating osteoporosis A pharmaceutical composition for treating osteoporosis which comprises as an active ingredient an effective amount of one or more compounds selected from the group comprising humulone, cohumulone, adhumulone, isohumulone, isocohumulone and isoadhumulone in combination with a pharmaceutically acceptable carrier or excipient. Humulone, cohumulone, adhumulone are the compounds belonging to .alpha. acids which are an ingredient extracted from hops, whilst isohumulone, isocohumulone and isoadhumulone are the compounds belonging to iso .alpha. acid derivatives which are isomers of .alpha. acids. The above described compounds have a bone resorption inhibiting activity and are useful for treating osteoporosis.
The blink reflex (BR) is integrated at the brainstem; however, it is modulated by inputs from various structures such as the striatum, globus pallidus, substantia nigra, and nucleus raphe magnus but also from afferent input from the peripheral nervous system. Therefore, it provides information about the pathophysiology of numerous peripheral and central nervous system disorders. The BR is a valuable tool for studying the integrity of the trigemino-facial system, the relevant brainstem nuclei, and circuits. At the same time, some neurophysiological techniques applying the BR may indicate abnormalities involving structures rostral to the brainstem that modulate or control the BR circuits. This is a state-of-the-art review of the clinical application of BR modulation; physiology is reviewed in part 1. In this review, we aim to present the role of the BR and techniques related to its modulation in understanding pathophysiological mechanisms of motor control and pain disorders, in which these techniques are diagnostically helpful. Furthermore, some BR techniques may have a predictive value or serve as a basis for follow-up evaluation. BR testing may benefit in the diagnosis of hemifacial spasm, dystonia, functional movement disorders, migraine, orofacial pain, and psychiatric disorders. Although the abnormalities in the integrity of the BR pathway itself may provide information about trigeminal or facial nerve disorders, alterations in BR excitability are found in several disease conditions. BR excitability studies are suitable for understanding the common pathophysiological mechanisms behind various clinical entities, elucidating alterations in top-down inhibitory systems, and allowing for follow-up and quantitation of many neurological syndromes.
BACKGROUND: The burgeoning demand for hepatectomy in elderly patients with hepatocellular carcinoma (HCC) necessitates improved perioperative care. Geriatric populations frequently experience functional decline and frailty, predisposing them to adverse postoperative outcomes. The Barthel Index serves as a reliable measure for assessing functional capacity, and this study evaluates its impact on surgical textbook outcomes (TOs) in elderly HCC patients.
METHODS: A multicenter retrospective cohort study analyzed elderly patients (≥70 years) following hepatectomy for HCC between 2013 and 2021. Utilizing a Barthel Index cut-off value of 85, patients were divided into two groups: with and without preoperative functional decline and frailty. The primary outcome was the rate of TO, encompassing seven criteria. TO rates were compared between groups, and multivariate logistic regression analyses identified independent risks for achieving TOs.
RESULTS: Of 497 elderly patients, 157 (31.6 ​%) exhibited preoperative functional decline and frailty (Barthel Index score <85). The overall TO rate was 58.6 ​%. Patients with preoperative Barthel Index score <85 had significantly lower TO rates compared to patients with score ≥85 (29.3 ​% vs. 72.1 ​%, P ​< ​0.001). Multivariate analysis revealed preoperative Barthel Index score <85 as an independent risk for achieving TO (odds ratio 3.413, 95 ​% confidence interval 1.879-6.198, P ​< ​0.001). Comparable results were observed in the subgroups of patients undergoing open and laparoscopic hepatectomy.
CONCLUSION: Preoperative Barthel Index-based assessment of functional decline and frailty significantly predicts TOs following hepatectomy in elderly HCC patients, enabling identification of high-risk patients and informing preoperative management and postoperative care within geriatric oncology.
Well-differentiated liposarcoma (WDLS) displays amplification of genes on chromosome 12 (Chr12) in supernumerary ring or giant marker chromosomes. These structures have been suggested to develop through chromothripsis, followed by circularization and breakage-fusion-bridge (BFB) cycles. To test this hypothesis, we compared WDLSs with Chr12 amplification in rod-shaped chromosomes with WDLSs with rings. Both types of amplicons share the same spectrum of structural variants (SVs), show higher SV frequencies in Chr12 than in co-amplified segments, have SVs that fuse the telomeric ends of co-amplified chromosomes, and lack interspersed deletions. Combined with the finding of cells with transient rod-shaped structures in tumors with ring chromosomes, this suggests a stepwise process starting with the gain of Chr12 material that, after remodeling which does not fit with classical chromothripsis, forms a dicentric structure with other chromosomes. Depending on if and when telomeres from other chromosomes are captured, circularized or linear gain of 12q sequences will predominate.