anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
In postmarketing experience, overdose with lorazepam has occurred predominantly in combination with alcohol and/or other drugs. Therefore, in the management of overdosage, it should be borne in mind that multiple agents may have been taken.  


Symptoms

Overdosage of benzodiazepines is usually manifested by varying degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, paradoxical reactions, dysarthria and lethargy. In more serious cases, and especially when other drugs or alcohol were ingested, symptoms may include ataxia, hypotonia, hypotension, cardiovascular depression, respiratory depression, hypnotic state, coma, and death.

MANAGEMENT

General supportive and symptomatic measures are recommended; vital signs must be monitored and the patient closely observed. When there is a risk of aspiration, induction of emesis is not recommended. Gastric lavage may be indicated if performed soon after ingestion or in symptomatic patients. Administration of activated charcoal may also limit drug absorption. Hypotension, though unlikely, usually may be controlled with norepinephrine bitartrate injection. Lorazepam is poorly dialyzable. Lorazepam glucuronide, the inactive metabolite, may be highly dialyzable.

The benzodiazepine antagonist flumazenil may be used in hospitalized patients as an adjunct to, not as a substitute for, proper management of benzodiazepine overdose. The prescriber should be aware of a risk of seizure in association with flumazenil treatment, particularly in long-term benzodiazepine users and in cyclic antidepressant overdose. The complete flumazenil package insert including CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS should be consulted prior to use.
This study combines alcohol challenge and progressive ratio self-administration methodologies to test the effects of each of the three dimensions of the Addictions Neuroclinical Assessment (ANA) on motivation for alcohol use. The experimental design consists of a translational study in which 210 individuals with current AUD (mild-to-severe) will complete an intravenous (IV) alcohol administration followed by a progressive ratio self-administration paradigm, where participants must press a button a number of times to receive an infusion of alcohol. All participants will be phenotyped for the three dimensions of the ANA, including incentive salience, negative emotionality, and executive dysfunction. For these models, the primary outcome in the progressive ratio self-administration paradigm will be: (a) breakpoint (i.e., the point in the progressive ratio model at which the participant stops button presses for alcohol) and (b) peak BrAC (i.e., the highest level of BrAC reached in the trial). At baseline and after the target BrAC of 0.06 g/dl in the alcohol challenge component of the paradigm, participants will report on (a) alcohol craving, (b) negative mood, and (c) loss of control over drinking. All participants will provide blood samples at baseline and at target BrAC =0.06 g/dl for analyses of the proposed exploratory biomarkers of HPA axis activation (ACTH, cortisol) and inflammation (IL-6, IL-10, TNF-α, CRP). The successful completion of this project will advance translational science of AUD by testing the ANA framework within a conceptually rich and valid translational task of motivation for alcohol in humans. Advanced data analytic methods (i.e., machine learning) and careful attention to AUD severity as a marker to AUD stage, will result in clinically useful findings that can inform AUD assessment, treatment, and biomarker development.
Olfactory dysfunction is increasingly recognized as an early indicator of Alzheimer's disease (AD). Aberrations in GABAergic function and the excitatory/inhibitory (E/I) balance within the olfactory bulb (OB) have been implicated in olfactory impairment during the initial stages of AD. While the neuregulin 1 (NRG1)/ErbB4 signaling pathway is known to regulate GABAergic transmission in the brain and is associated with various neuropsychiatric disorders, its specific role in early AD-related olfactory impairment remains incompletely understood. This study demonstrated that olfactory dysfunction preceded cognitive decline in young adult APP/PS1 mice and was characterized by reduced levels of NRG1 and ErbB4 in the OB. Further investigation revealed that deletion of ErbB4 in parvalbumin interneurons reduced GABAergic transmission and increased hyperexcitability in mitral and tufted cells (M/Ts) in the OB, thereby accelerating olfactory dysfunction in young adult APP/PS1 mice. Additionally, ErbB4 deficiency was associated with increased accumulation of Aβ and BACE1-mediated cleavage of APP, along with enhanced CDK5 signaling in the OB. NRG1 infusion into the OB was found to enhance GABAergic transmission in M/Ts and alleviate olfactory dysfunction in young adult APP/PS1 mice. These findings underscore the critical role of NRG1/ErbB4 signaling in regulating GABAergic transmission and E/I balance within the OB, contributing to olfactory impairment in young adult APP/PS1 mice, and provide novel insights for early intervention strategies in AD. This work has shown that ErbB4 deficiency increased the burden of Aβ, impaired GABAergic transmission, and disrupted the E/I balance of mitral and tufted cells (M/Ts) in the OB, ultimately resulting in olfactory dysfunction in young adult APP/PS1 mice. NRG1 could enhance GABAergic transmission, rescue E/I imbalance in M/Ts, and alleviate olfactory dysfunction in young adult APP/PS1 mice. OB: olfactory bulb, E/I: excitation/inhibition, Pr: probability of release, PV: parvalbumin interneurons, Aβ: β-amyloid, GABA: gamma-aminobutyric acid.
This invention relates to a two-part system useful for treating proteinaceous substrates. The two-part system has a first part comprising a water-soluble/dispersible reactive imido or polyimido compound and a second part comprising a nucleophilic catalytic agent. The polyimido compounds may be selected from the group consisting of polysuccinimide compounds, polyglutimide compounds, and copolymers of thereof. The imido or polyimido compound may also comprise a functionalizing moiety that provides functionality to the imido or polyimido compound and is preferably derived from a nucleophilic moiety selected from the group consisting of amines, alcohols, phenols, thiols, and carboxylates; and a water-solubilizing/dispersing moiety that provides water-solubility and/or water-dispersibility to the polyimido compound and is preferably derived from a nucleophilic moiety selected from the group consisting of amines, alcohols, phenols, thiols, and carboxylates. The nucleophilic catalytic agent is believed to catalyze nucleophilic substitution of the imido or polyimido compound by the proteinaceous substrate. The invention also pertains to a method for treating a proteinaceous substrate with the two-part system and to a composition comprising a mixture of the imido or polyimido compound and the nucleophilic catalytic agent.
Patients undergo RT (3DCRT or IMRT) daily Monday-Friday for up to 7-8 weeks and receive chemotherapy based on physician's choice as in Arm I. Patients also receive atezolizumab IV over 30-60 minutes on day 1 of each cycle. Treatment repeats every 21 days for up to 9 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo a TURBT with bladder biopsy at randomization and week 18 as well as cystoscopy at randomization, at weeks 18, 30, 42, 54, then every 3 months through year 2, followed by every 6months through year 5 and CT or MRI at randomization, at weeks 18, 30, 42, 54, then every 6 months through year 2, followed by every 12 months through year 5.
PURPOSE:To obtain a sustained release preparation of nicardipine hydrochloride useful as an agent for the treatment of cerebrovascular disorder, hypertension, stenocardia, etc., by treating nicardipine hydrochloride crystal with D-mannitol and a polymeric base. CONSTITUTION:This sustained release preparation is produced by dissolving nicardipine hydrochloride crystal in a proper solvent (e.g. methanol) together with D-mannitol and a polymeric base such as cellulose derivative, polyvinyl pyrrolidone and polyvinyl acetal diethylaminoacetate and spraying and drying the solution. The amounts of D-mannitol and polymeric base are 0.1-1,000 pts.wt. each based on 1 pt.wt. of nicardipine hydrochloride crystal. The dissolution rate of nicardipine hydrochloride in the intestines can be improved while maintaining the crystalline state. An especially excellent sustained release preparation can be produced by treating the above sustained release preparation with a polymeric base such as polyethyl acrylate or polymethyl methacrylate to control the dissolution rates of the nicardipine hydrochloride in the stomach and in the intestines.
The potential patients will be screened by the STOP-Bang questionnaire. Those with a score ≥4 will be randomized into Sleep Study group or Oximetry group. The patients in the Sleep Study group will be referred to a sleep medicine specialist who is part of the Bariatric Surgery Psychosocial Program. In the Sleep Study group, patients will undergo sleep studies overnight in a sleep laboratory. At the same time, they will also wear the oximeter wristwatch to measure overnight oximetry. Depending on the sleep study results and medical history, a decision will be made regarding therapeutic options. If the patient has severe sleep apnea (AHI\>30) or moderate sleep apnea (AHI\>15 to \<30) with significant co-morbidities (e.g. cardiovascular disease, diabetes), CPAP treatment will be recommended. For mild sleep apnea (AHI\>5 to \<15) or moderate sleep apnea without significant co-morbidities, CPAP will not be required. If patient is not able to tolerate or refuses CPAP, dental device and positional therapy will be recommended.

The patients in the Oximetry group will undergo overnight pulse oximetry. The patients with ODI\>10 events/hour will be referred to the sleep medicine specialist. Since the patients with ODI\>10 had a high probability 69%) to have moderate and severe OSA. A split- night PSG will be employed to confirm OSA diagnosis and to titrate CPAP with in patients with ODI\>10. The 1st part of the night will be a sleep study and depending on AHI, CPAP titration will be done for the 2nd part of the night. Compared to Sleep Study group, only one night instead of two nights of sleep studies is needed in patients with ODI\>10 events/hour. The patients with ODI ≤ 10 events/h will undergo surgery with routine care plus sleep apnea perioperative precautions.
Hydrocortisone Rectal Suspension, USP should be used with caution where there is a probability of impending perforation, abscess or other pyogenic infection; fresh intestinal anastomoses; obstruction; or extensive fistulas and sinus tracts. Use with caution in presence of active or latent peptic ulcer; diverticulitis; renal insufficiency; hypertension; osteoporosis; and myasthenia gravis.

Steroid therapy might impair prognosis in surgery by increasing the hazard of infection. If infection is suspected, appropriate antibiotic therapy must be administered, usually in larger than ordinary doses.

Drug-induced secondary adrenocortical insufficiency may occur with prolonged Hydrocortisone Rectal Suspension, USP therapy. This is minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

There is an enhanced effect of corticosteroids on patients with hypothyroidism and in those with cirrhosis.

Corticosteroid should be used cautiously in patients with ocular herpes simplex because of possible corneal perforation.

The lowest possible dose of corticosteroid should be used to control the conditions under treatment, and when reduction in dosage is possible, the reduction should be gradual.

Psychic derangement may appear when corticosteroids are used, ranging from euphoria, insomnia, mood swings, personality changes, and severe depression, to frank psychotic manifestations. Also, existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.

Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinemia.
1432095 Photo-oxidation sterilization BAYLOR COLLEGE OF MEDICINE 2 April 1974 [16 April 1973 26 Dec 1973] 14537/74 Heading C1C [Also in Divisions A5 and C5] A photo-oxidation process for sterilizing liquid contaminated with organisms comprises: sensitizing the organisms by adjusting the pH of the liquid to basic, intimately mixing from 0À1 to 100% by wt. of a photo-reactive dye with the liquid, exposing the water-dye mixture to a light of wavelength and intensity sufficient to excite the dye thereby inactivating the organisms. The process is suitable for treating liquid wastes, e.g. sewage, water, oil contaminated with water, oil-water mixtures or a biological. The dye may be removed after exposure to light. A photo-oxidation treating system is also claimed. This comprises a conduit, means for introducing influent and injecting a base into the conduit, means for mixing base and influent, means for injecting a dye into the conduit and into the influent, mixer means for mixing the influent and the dye to form a water-dye mixture, a chamber downstream of the mixer means and connected to the conduit, a photooxidizing light in the chamber having a wavelength and intensity sufficient to excite the dye, a discharge conduit extending from the chamber whereby the water-dye mixture flows through the chamber and into exposure with the photooxidizing light, and is discharged from the chamber. In Example 1 raw sewage was treated with a cation resin exchanger (not charged) to remove divalent cations, treated with methylene blue (1% by wt. at pH 10À5 and 37 C. for ¢ hour). It was then exposed to a photo-oxidizing light for 30 sees. The treated product did not contain any detectable microbiological flora. In Example 2 sewage containing added viruses was treated so that these were removed.
An increasing number of elderly individuals are experiencing postoperative cognitive dysfunction (POCD) problems after undergoing hip replacement surgery, with gut microbiota metabolites playing a role in its pathogenesis. Among these, the specific effects of trimethylamine N-oxide (TMAO) on POCD are still unclear. This study aimed to explore the role of TMAO on cognitive dysfunction and underlying mechanisms in mice. The POCD model was created through femoral fracture surgery in elderly mice, followed by cognitive function assessments using the Morris Water Maze and Novel Object Recognition tests. The gut microbiota depletion and fecal microbiota transplantation were performed to examine the relationship between TMAO levels and cognitive outcomes. The effects of TMAO treatment on cognitive dysfunction, microglial activation, and inflammatory cytokine levels in the brain were also evaluated, with additional assessment of the role of microglial ablation in reducing TMAO-induced cognitive impairment. Elevated TMAO levels were found to be associated with cognitive decline in mice following femoral fracture surgery, with gut microbiota depletion mitigating both TMAO elevation and cognitive dysfunction. In contrast, fecal microbiota transplantation from postoperative mice resulted in accelerated cognitive dysfunction and TMAO accumulation in germ-free mice. Furthermore, TMAO treatment worsened cognitive deficits, neuroinflammation, and promoted microglial activation, which were reversed through the ablation of microglia. TMAO exacerbates cognitive dysfunction and neuroinflammation in POCD mice, with microglial activation playing a crucial role in this process. Our findings may provide new therapeutic strategies for managing TMAO-related POCD and improving the quality of life for elderly patients.
Age-related macular degeneration (AMD) is a leading cause of blindness featuring pathogenic neovascularization of the choroidal vasculature (CNV). Although systemic immunity plays a role in AMD, the ocular signals that recruit and activate immune cells remain poorly defined. Using single-cell RNA sequencing, we prospectively profile peripheral blood mononuclear cells from 65 individuals including AMD and controls, which we integrate with existing choroid data. We generate a network of choroid-peripheral immune interactions dysregulated in AMD, including known AMD-relevant gene vascular endothelial growth factor (VEGF) receptor 2. Additionally, we find CYR61 is upregulated in choroidal veins and may signal to circulating monocytes. In mice, we validate that CYR61 is abundant in endothelial cells within CNV lesions neighboring monocyte-derived macrophages. Mechanistically, CYR61 activates macrophage anti-angiogenic gene expression, and ocular Cyr61 knockdown increases murine CNV size, indicating CYR61 inhibits CNV. This study highlights the potential of multi-tissue human datasets to identify disease-relevant and potentially therapeutically modifiable targets.
Children between the age of 5 and \<8 years who are patients of the participating investigators will be screened for participation in the study. This may be at a regularly planned visit or the investigators may invite children who would be suitable candidates. Children who agree to participate will be invited to come back to the clinic on a single Study Day and will be randomised to a particular sequence of flavours. On the Study Day, all children will be given 3 different flavoured samples of Eslicarbazepine acetate (ESL) oral suspension for tasting, in the sequence to which they were randomised, in a double-blind, standardized setting. Each sample will consist of 2.5 mL and is to be given with a spoon in a double-blind manner, and is not to be swallowed. After tasting and spitting out each sample the child will be asked to rate the taste on a 10 cm visual analogue scale incorporating a facial hedonic scale. At the end of the session, the child will also be asked which flavour they thought tasted the best and which tasted the worst, to assess overall taste. A follow-up telephone contact interview will be performed between 1 and 4 days after the Study Day to collect adverse event (AE) data.
Informed written consent was taken from all the participants. Participants were asked to discontinue any topical or systemic antipruritic drugs, for least 1 week prior to the study. Demographic, clinical and laboratory data (complete blood count, renal function tests, liver function tests, serum electrolytes and ultrasound abdomen) was evaluated at baseline. Glomerular Filtration Rate (GFR) and stage of chronic kidney disease was calculated. Participants were randomly allocated to two groups. One group received loratadine 10mg daily and the other received gabapentin 100mg daily. Those participants undergoing hemodialysis received their respective dose after the dialysis session. Both groups were given treatment for 4 weeks. Participants were asked to grade the severity of pruritus on a numerical rating scale and also answer the Dermatology Life Quality Index Questionnaire.These proformas were filled once at the start of the study, at 2 weeks and then at the end of study i.e. 4 weeks. Participants were also asked to report any adverse events, if occurred.

The Statistical Package for the Social Sciences (SPSS) version 25.0 was used to analyze the data. Qualitative data (like gender, dialysis status, etc.) was expressed in the form of frequency and percentages while quantitative data (like age, weight, serum creatinine levels, etc.) was represented as mean and standard deviations (Mean±SD). The reduction in scores of numerical rating scale and Dermatology Life Quality Index Questionnaire was calculated from baseline. Mean reduction in scores were compared between the two groups and independent sample t-test was applied. p-value \<0.05 was considered as significant.
The environment of the test laboratory affects the reproducibility of treatment effects on physiological phenotypes of rodents and may be attributed to the plasticity of the epigenome due to nutrient-gene-environment interactions. Here, we explored the reproducibility of adding a multi-vitamin-mineral (MVM) mix to a nutrient-balanced high-fat (HF) diet on obesity, insulin resistance (IR), and gene expression in the tissues of adult male mice. Experiments of the same design were conducted in three independent animal facilities. Adult C57BL/6J male mice were fed an HF diet for 6 weeks (diet induced-obesity model) and then continued for 9-12 weeks on the HF diet with or without 5-fold additions of vitamins A, B1, B6, B12, Zn, and 2-fold Se. The addition of the MVM affected body weight, fat mass, gene expression, and markers of IR in all three locations (p < 0.05). However, the direction of the main effects was influenced by the interaction with the experimental location and its associated environmental conditions known to affect the epigenome. In conclusion, MVM supplementation influenced phenotypes and expression of genes related to adipose function in obese adult male mice, but the experimental location and its associated conditions were significant interacting factors. Preclinical studies investigating the relationship between diet and metabolic outcomes should acknowledge the plasticity of the epigenome and implement measures to reproduce studies in different locations.
Epidemiological studies have revealed an inverse relationship between the incidence of Alzheimer's disease (AD) and various cancers, including colorectal cancer (CRC). We aimed to determine whether the incidence of CRC is reduced in AD-like mice and whether gut microbiota confers resistance to tumorigenesis through inducing inflammatory tolerance using 16S ribosomal RNA gene sequencing and fecal microbiota transplantation (FMT). AD-like mice experienced a significantly decreased incidence of CRC tumorigenesis induced by azoxymethane-dextran sodium sulfate as evidenced by suppressed intestinal inflammation compared with control mice. However, FMT from age-matched control mice reversed the inhibitory effects on the tumorigenesis of CRC and inflammatory response in AD-like mice. The key bacterial genera in gut microbiota, including Prevotella, were increased in both the AD-like mice and in patients with amnestic mild cognitive impairment (aMCI) but were decreased in patients with CRC. Pretreatment with low-dose Prevotella-derived lipopolysaccharides (LPS) induced inflammatory tolerance both in vivo and in vitro and inhibited CRC tumorigenesis in mice. Imbalanced gut microbiota increased intestinal barrier permeability, which facilitated LPS absorption from the gut into the blood, causing cognitive decline in AD-like mice and patients with aMCI. These data reveal that intestinal Prevotella-derived LPS exerts a resistant effect to CRC tumorigenesis via inducing inflammatory tolerance in the presence of AD. These findings provide biological evidence demonstrating the inverse relationship between the incidence of AD and CRC.
Participants will receive RO7515629 intravenously, as a single agent on cycle 0 day -7 and 7 days later on cycle 1 day 1 followed by every three-week dosing frequency. In case of toxicity, step up dosing (single or double) may be implemented. Treatment may continue for up to 12 months maximum or until progression, loss of clinical benefit, intolerable toxicity, withdrawal from study treatment or death.
The mothers who were included in the control group were informed about the use of milking pumps in the routine application of the hospital, the data collection form and the state anxiety scale were filled out on the first day. These mothers were told by the researcher how to fill out the breast milk follow-up form for 4 days as long as they were in the hospital. Milk amounts are measured in ml. On the last day, the state anxiety scale has been filled.