anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Holiday Heart Syndrome (HHS) is caused by excessive binge alcohol consumption, and atrial fibrillation (AF) is the most common arrhythmia among HHS patients. AF is associated with substantial morbidity and mortality, making its prevention and treatment of high clinical interest. This study defines the anti-AF action of Alda-1 (an established cardioprotective agent) and the underlying mechanisms of the action in our well-characterized HHS and cellular models. We found that Alda-1 effectively eliminated binge alcohol-evoked Ca2+ triggered activities (Ca2+ waves, prolonged Ca2+ transient diastolic decay) and arrhythmia inducibility in intact mouse atria. We then demonstrated that alcohol impaired human RyR2 channels (isolated from organ donors' hearts). The functional role of alcohol-caused RyR2 channel dysfunction in Ca2+ triggered arrhythmic activities was evidenced in a unique transgenic mouse model with a loss-of-function mutation (RyR2E4872Q+/-). Alda-1 is known to activate aldehyde dehydrogenase 2 (ALDH2), a key enzyme in alcohol detoxification. However, we found an increased level of ALDH2 and a preserved normal balance of pro- vs anti-apoptotic signaling in binge alcohol exposed hearts and H9c2 differentiated myocytes, which suggests that the link of alcohol-ALDH2-apoptosis is unlikely to be a key factor leading to binge alcohol-evoked arrhythmogenicity. We have previously reported that binge alcohol-activated stress response kinase JNK2 causatively drives Ca2+-triggered atrial arrhythmogenicity. Here, we found that JNK2-specific inhibition in either isolated human RyR2 channels or intact mouse atria abolished alcohol-evoked RyR2 channel dysfunction and Ca2+ triggered arrhythmic activities, suggesting a strong alcohol-JNK2-RyR2 interaction in atrial arrhythmogenicity. Furthermore, we revealed, for the first time, that Alda-1 suppresses JNK2 (but not JNK1) enzyme activity independently of ALDH2, which in turn alleviates binge alcohol-evoked Ca2+ triggered atrial arrhythmogenesis. Our findings provide novel mechanistic insights into the anti-arrhythmic action of Alda-1 and suggest that Alda-1 represents a potential preventative agent for AF management for HHS patients.
Functional nausea patients with a score of 0-2 on the BARF (BAxter Retching Faces) scale will be given questionnaires and testing by EGG and/or MGG after an overnight fast to determine nausea parameters. They will also have a EKG and do some testing after being fed a protein bar.
Mitochondrial calcium overload plays an important role in the neurological insults in seizure. The Rab7 GTPase-activating protein, Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15), is involved in the regulation of mitochondrial calcium dynamics by mediating mitochondria-lysosome membrane contact. However, whether TBC1D15-regulated mitochondria-lysosome membrane contact and mitochondrial calcium participate in neuronal injury in seizure is unclear. We aimed to investigate the effect of TBC1D15-regulated mitochondria-lysosome membrane contact on epileptiform discharge-induced neuronal damage and further explore the underlying mechanism. Lentiviral vectors (Lv) infection and stereotaxic adeno-associated virus (AAV) injection were used to regulate TBC1D15 expression before establishing in vitro epileptiform discharge and in vivo status epilepticus (SE) models. TBC1D15's effect on inter-organellar interactions, mitochondrial calcium levels and neuronal injury in seizure was evaluated. The results showed that abnormalities in mitochondria-lysosome membrane contact, mitochondrial calcium overload, mitochondrial dysfunction, increased levels of reactive oxygen species, and prominent neuronal damage were partly relieved by TBC1D15 overexpression, whereas TBC1D15 knockdown markedly deteriorated these phenomena. Further examination revealed that epileptiform discharge-induced mitochondrial calcium overload in primary hippocampal neurons was closely associated with abnormal mitochondria-lysosome membrane contact. This study highlights the crucial role played by TBC1D15-regulated mitochondria-lysosome membrane contact in epileptiform discharge-induced neuronal injury by alleviating mitochondrial calcium overload.
An emulsified mouth wash comprises from 0.25 to 10 per cent by weight of an ethanol-soluble organopolysiloxane having an average of from 1 to 3 monovalent hydrocarbon radicals per silicon atom, these radicals being alkyl, aryl, or aralkyl; from 0.05 to 20 per cent by weight of a non-toxic emulsifying agent; from 1 to 50 per cent by weight of ethanol; and from 30 to 98.7 per cent by weight of water.  Specified organic radicals for the polysiloxanes are methyl, ethyl, butyl, octadecyl, phenyl, tolyl, chlorophenyl, xenyl, and benzyl.  The ethanol may be used alone or admixed with diluents such as glycerine, ethylene or propylene glycol, dipropylene glycol or polyglycols. Specified emulsifying agents are glyceryl mono-oleate, propylene glycol monolaurate, glyceryl monolaurate, monostearate, or oleostearate, polyoxethylene stearate, polyethylene glycol stearate, gums such as tragacanth, arabic, paraya and locust bean; and the amides of sulphonated fatty acids.  Other specified additions are boric acid, benzoic acid, zinc chloride, sodium chloride, thymol, zinc phenol sulphonate, phenol, hexylresorcinol, oils of winter green, peppermint, clove, sage, sassafras, lemon, and marjoram, sucrose, saccharine, caramel and cinnamon.ALSO:An emulsified mouth wash comprises from 0.25 to 10 per cent by weight of an ethanol-soluble organopolysiloxane having an average of from 1 to 3 monovalent hydrocarbon radicals per silicon atom, these radicals being alkyl, aryl, or arakyl; from 0.05 to 20 per cent by weight of a non-toxic emulsifying agent; from 1 to 50 per cent by weight of ethanol; and from 30 to 98.7 per cent by weight of water.  Specified organic radicals for the polysiloxanes are methyl, ethyl, butyl, octadecyl, phenyl, tolyl, chlorophenyl, xenyl, and benzyl.  The ethanol may be used alone or admixed with diluents such as glycerine ethylene or propylene glycol, dipropylene glycol or polyglycols. Specified emulsifying agents are glyceryl mono-oleate, propylene glycol mono-laurate, glyceryl monolaurate, monostearate, or oleosterate, polyoxethylene stearate, polyethylene glycol stearate, gums such as tragacanth, arabic, paraya and locust bean; and the amides of sulphonated fatty acids.  Other specified additions are boric acid, benzoic acid, zinc chloride, sodium chloride, thymol, zinc phenol sulphonate, phenol, hexylresorcinol, oils of winter green, peppermint, clove, sage, sassafras, lemon, and marjoram, sucrose, saccharine, caramel and cinnamon.
Intravenous fluid administration was administered as soon as possible following randomization (not to exceed 12 hours prior to anticipated contrast exposure) and continued for 12 hours post CT. Patients randomized to the experimental arm received intravenous normal saline plus NAC 10 grams IV (5 g pre and 2.5 g at 6 and 12 hours post-exposure) for a total of 3 doses.
Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.
PURPOSE: Despite understanding the connection between obesity and fracture risk, there is limited research on the implications of lower limb fractures on subsequent changes in body mass index (BMI). Our study aimed to assess the impact of lower limb fractures on BMI alterations over an 18-month period.
METHODS: A multi-center, prospective cohort study was conducted between January 2021 to June 2023, involving 494 adults with lower limb fractures. Participants were recruited within 2 weeks post-injury and were assessed for demographics, injury details, and weight at seven distinct time points. By 18 months, the primary outcome was the mean weight gain.
RESULTS: The average age of the participants was 39 (± 12.7) with a baseline weight and BMI of 80.4 kg and 27.6, respectively. At the 18-month follow-up, 75% of patients experienced an average weight increase in 4 kg (± 5.39 kg), equating to a BMI rise of 1.39 (± 1.88). Most patients attributed weight changes to their injury, with nearly half expressing distress from their weight change. Only 37% believed that they had resumed their previous activity levels by the final follow-up. Approximately 31% of the patients sought some form of external weight management care in the form of nutritionist advice, training programs, medication and weight management procedures.
CONCLUSIONS: Lower limb fractures significantly affect weight gain over an 18-month period, with substantial psychological and physical consequences. Healthcare providers should anticipate potential weight gain post-fracture and incorporate strategies addressing both physical and mental aspects of rehabilitation to enhance recovery outcomes. Early and even immediate weight bearing may play a pivotal role in mitigating weight changes and returning the patient to their previous level of activity. Further detailed studies focusing on different fractures and postoperative interventions are recommended.
SPRAVATO ®contains esketamine hydrochloride, a non-competitive N-methyl- D-aspartate (NMDA) receptor antagonist. Esketamine is the S-enantiomer of racemic ketamine. The chemical name is (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride. Its molecular formula is C 13H 16ClNO.HCl and its molecular weight is 274.2. The structural formula is: 

Esketamine hydrochloride is a white or almost white crystalline powder that is freely soluble in water and in methanol, and soluble in ethanol.

SPRAVATO nasal spray is intended for nasal administration. Esketamine hydrochloride is contained as a solution in a stoppered glass vial within the nasal spray device. Each device delivers two sprays with a total of 32.3 mg of esketamine hydrochloride (equivalent to 28 mg of esketamine) in 0.2 mL of a clear, colorless aqueous solution with a pH of 4.5.

The inactive ingredients are citric acid monohydrate, edetate disodium, sodium hydroxide, and water for injection.
FIELD: medicine, ophthalmology. SUBSTANCE: invention relates to preparations used for treatment of sicknesses associated with metabolic disorders and eye retina and cornea inflammation. Drug is 0.02% isotonic solution of equinochrome di- and trisodium salt ("Gistokhrom"). This drug is used in sicknesses associated with disorder of metabolic and inflammatory processes in retina, vascular membrane and cornea for improvement of trophics, edema decrease and acceleration of epithelization. Drug is used in proliferative processes, degenerations and hemophthalms of different genesis and in contusia and eye penetrating wounding also. Drug shows retinoprotective, anti-inflammatory and anticataractous properties and shows good tolerance by patients. EFFECT: enhanced effectiveness of preparation. 1 ex
Agave inulin 2.3 g, by mouth, every 12 hours for 3 months. Plus recommendations to decrease calories intake an do exercise.
Inflammatory bowel disease (IBD) is strongly related to the occurrence of accumulation of toxic reactive oxygen species (ROS), inflammation of the mucosa, and an imbalance of intestinal microbes. However, current treatments largely focus on a single factor, yielding unsatisfactory clinical outcomes. Herein, we report a biocompatible and IBD-targeted metabolic nanoregulator (TMNR) that synergistically regulates cellular and bacterial metabolism. The TMNR comprises a melanin-gallium complex (MNR) encapsulated within a thermosensitive and colitis-targeting hydrogel, all composed of natural and FDA-approved components. The TMNR confers superior broad-spectrum antioxidant properties, effectively scavenging reactive oxygen species (ROS) and blocking inflammatory signaling pathways. The presence of Ga3+ in TMNR selectively disrupts iron metabolism in pathogenic microorganisms due to its structural resemblance to the iron atom. Additionally, incorporating a thermosensitive injectable hydrogel enables targeted delivery of TMNR to inflammatory regions, prolonging their retention time and providing a physical barrier function for optimizing IBD treatment efficacy. Collectively, TMNR effectively modulates the redox balance of inflamed colonic epithelial tissue and disrupts iron metabolism in pathogenic microorganisms, thereby eliminating inflammation and restoring intestinal homeostasis against IBD. Hence, this work presents a comprehensive approach for precise spatiotemporal regulation of the intestinal microenvironmental metabolism for IBD treatment.
Long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of an NSAID results in a dose-dependent decrease in prostaglandin synthesis and, secondarily, in a reduction of renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state.

### Advanced Renal Disease

No information is available from controlled clinical studies regarding the use of nabumetone tablets in patients with advanced renal disease. Therefore, treatment with nabumetone tablets is not recommended in these patients with advanced renal disease. If nabumetone tablet therapy must be initiated, close monitoring of the patient's renal function is advisable.

Because nabumetone undergoes extensive hepatic metabolism, no adjustment of the dosage of nabumetone is generally necessary in patients with mild renal insufficiency; however, as with all NSAIDs, patients with impaired renal function should be monitored more closely than patients with normal renal function (see CLINICAL PHARMACOLOGY). In subjects with moderate renal impairment (creatinine clearance 30 to 49 mL/min) there is a 50% increase in unbound plasma 6MNA and dose adjustment may be warranted. The oxidized and conjugated metabolites of 6MNA are eliminated primarily by the kidneys.
Zolpidem tartrate, like other sedative-hypnotic drugs, has CNS-depressant effects. Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression [see Drug Interactions (7.1)] . Dosage adjustments of zolpidem tartrate and of other concomitant CNS depressants may be necessary when zolpidem tartrate is administered with such agents because of the potentially additive effects. The use of zolpidem tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended [see Dosage and Administration (2.3)]. 

The risk of next-day psychomotor impairment, including impaired driving, is increased if zolpidem tartrate is taken with less than a full night of sleep remaining (7 to 8 hours); if a higher than the recommended dose is taken; if coadministered with other CNS depressants or alcohol; or if coadministered with other drugs that increase the blood levels of zolpidem. Patients should be warned against driving and other activities requiring complete mental alertness if zolpidem tartrate is taken in these circumstances [see Dosage and Administration (2), Clinical Studies (14.3)]. 

Vehicle drivers and machine operators should be warned that, as with other hypnotics, there may be a possible risk of adverse reactions including drowsiness, prolonged reaction time, dizziness, sleepiness, blurred/double vision, reduced alertness, and impaired driving the morning after therapy. In order to minimize this risk a full night of sleep (7-8 hours) is recommended.

Because Zolpidem tartrate can cause drowsiness and a decreased level of consciousness, patients, particularly the elderly, are at higher risk of falls.
A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of sedative/hypnotics. Some of these changes may be characterized by decreased inhibition (e.g., aggressiveness and extroversion that seem out of character), similar to effects produced by alcohol and other CNS depressants. Other reported behavioral changes have included bizarre behavior, agitation, hallucinations and depersonalization. Amnesia and other neuropsychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of sedative/hypnotics.

Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported. These events can occur in sedative-hypnotic-naïve as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving may occur with eszopiclone alone at therapeutic doses, the use of alcohol and other CNS depressants with eszopiclone appears to increase the risk of such behaviors, as does the use of eszopiclone at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of eszopiclone should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviors (e.g., preparing and eating food, making phone calls or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events.

It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above are drug-induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
The iCBT program (clinician follow-up with the therapist and 4 online modules) will be administered for 8 weeks. The four modules: "1) psychoeducation about emotions, including a functional nature of emotions; 2) alteration of antecedent cognitive misappraisals; 3) prevention of emotional avoidance; and 4) modification of emotion-driven \[behaviours\] (EDBs)", are adapted from The Unified Protocol (UP) for transdiagnostic treatment of emotional disorders. UP is a CBT consisting of four overarching themes- "increasing emotional awareness, facilitating flexibility in appraisals, identifying and preventing \[behavioural\] and emotional awareness, and situational and interoceptive exposure to emotion cues".
OBJECTIVE: To assess the cumulative rates of re-operations after hypospadias repair and evaluate long-term surgical outcomes at a tertiary paediatric urology centre.
PATIENTS AND METHODS: Retrospective analysis of 293 boys born between 1991 and 2003 undergoing hypospadias surgery was conducted. The study included 274 patients: 165 with distal, 34 with midshaft, and 75 with proximal hypospadias. Kaplan-Meier methods were used to evaluate the re-operation data.
RESULTS: The median age at primary surgery was 1.3 years, with a median follow-up of 14.4 years. The overall re-operation rate was 48.2%, with approximately half of the problems detected within the first 3 months after surgery. The risk of re-operation was correlated with hypospadias severity, with 5- and 15-year re-operation risks at 39.3% and 51.8%, respectively. Limitations of the study include its retrospective nature and variations in surgical techniques from current standards.
CONCLUSION: There is a significant risk of unplanned re-operations following hypospadias repair, increasing with the severity of the original condition. This underscores the need for extended follow-up and effective communication with patients and their families about the likelihood of requiring multiple surgeries for optimal outcomes.
Subjects will be randomized for the treatment of fish oil capsules. Subjects will take daily supplements of two or four fish oil capsules per day, 2 and 4 g respectively. Treatment will continue for 16 weeks. Fish oil capsules are enriched in omega-3 polyunsaturated fatty acids.
Abemaciclib (LY2835219) will be administered orally on a twice daily basis continuously for 28 days, which defines one cycle. The maximum treatment duration will be 2 years. Investigators plan to treat a maximum of 4 cohorts of research participants (dosage levels 1, 2, 3, and 4) with escalating doses of abemaciclib starting with dose level 1 (80% of adult dose). Dose escalation will be independent of Stratum A escalation. A cycle is defined as 28 days and the first 4 weeks of therapy will constitute the DLT-evaluation period. Participants must take abemaciclib by mouth as intact capsules.
The treatment of patients with metastatic prostate cancer (PCa) is considered to be a long‑standing challenge. Conventional treatments for metastatic PCa, such as radical prostatectomy, radiotherapy and androgen receptor‑targeted therapy, induce senescence of PCa cells to a certain extent. While senescent cells can impede tumor growth through the restriction of cell proliferation and increasing immune clearance, the senescent microenvironment may concurrently stimulate the secretion of a senescence‑associated secretory phenotype and diminish immune cell function, which promotes PCa recurrence and metastasis. Resistance to established therapies is the primary obstacle in treating metastatic PCa as it can lead to progression towards an incurable state of disease. Therefore, understanding the molecular mechanisms that underly the progression of PCa is crucial for the development of novel therapeutic approaches. The present study reviews the phenomenon of treatment‑induced senescence in PCa, the dual role of senescence in PCa treatments and the mechanisms through which senescence promotes PCa metastasis. Furthermore, the present review discusses potential therapeutic strategies to target the aforementioned processes with the aim of providing insights into the evolving therapeutic landscape for the treatment of metastatic PCa.