anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Since adequate human reproduction studies have not been done with corticosteroids, the use of these drugs in pregnancy, nursing mothers or women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and embryo or fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy, should be carefully observed for signs of hypoadrenalism.

Average and large doses of hydrocortisone or cortisone can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.

While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunization procedures should not be undertaken in patients who are on corticosteroids, especially on high dose, because of possible hazards of neurological complications and a lack of antibody response.
The safety and efficacy of NYMALIZE (nimodipine oral solution) in the treatment of patients with SAH is based on adequate and well-controlled studies of nimodipine oral capsules in patients with SAH. NYMALIZE (nimodipine oral solution) has comparable bioavailability to nimodipine oral capsules.

Nimodipine has been shown in 4 randomized, double-blind, placebo-controlled trials to reduce the severity of neurological deficits resulting from vasospasm in patients who have had a recent SAH (Studies 1, 2, 3, and 4).

The trials used doses ranging from 20-30 mg to 90 mg every 4 hours, with drug given for 21 days in 3 studies, and for at least 18 days in the other. Three of the four trials followed patients for 3-6 months. Three of the trials studied relatively well patients, with all or most patients in Hunt and Hess Grades I - III (essentially free of focal deficits after the initial bleed). Study 4 studied much sicker patients with Hunt and Hess Grades III - V. Studies 1 and 2 were similar in design, with relatively unimpaired SAH patients randomized to nimodipine or placebo. In each, a judgment was made as to whether any late-developing deficit was due to spasm or other causes, and the deficits were graded. Both studies showed significantly fewer severe deficits due to spasm in the nimodipine group; Study 2 showed fewer spasm-related deficits of all severities. No effect was seen on deficits not related to spasm. See Table 2. 

Study 3 was a 554-patient trial that included SAH patients with all grades of severity (89% were in Hunt and Hess Grades I-III). In Study 3, patients were treated with placebo or 60 mg of nimodipine every 4 hours. Outcomes were not defined as spasm related or not but there was a significant reduction in the overall rate of brain infarction and severely disabling neurological outcome at 3 months (Table 3):

Study 4 enrolled much sicker patients, (Hunt and Hess Grades III-V), who had a high rate of death and disability, and used a dose of 90 mg every 4 hours, but was otherwise similar to Study 1 and Study 2. Analysis of delayed ischemic deficits, many of which result from spasm, showed a significant reduction in spasm-related deficits. Among analyzed patients (72 nimodipine, 82 placebo), there were the following outcomes (Table 4).

When data were combined for Study 3 and Study 4, the treatment difference on success rate (i.e., good recovery) on the Glasgow Outcome Scale was 25.3% (nimodipine) versus 10.9% (placebo) for Hunt and Hess Grades IV or V. Table 5 demonstrates that nimodipine tends to improve good recovery of SAH patients with poor neurological status post-ictus, while decreasing the numbers with severe disability and vegetative survival.

A dose-ranging study comparing 30 mg, 60 mg, and 90 mg doses found a generally low rate of spasm-related neurological deficits but no dose response relationship.
Methods and systems for developing and manufacturing componentized drug product precursor modules that can be simply assembled to create customized drug products are disclosed. Each module contains components of a final drug product (e.g., active pharmaceutical ingredients, nutritional ingredients, and/or excipients) in a fixed mixture selected to maximize desired pharmaceutical characteristics (e.g., stability, manufacturing efficiency) and minimize cost. The modules can be extensively tested for quality and assembled immediately, or at a later time, in multiple combinations to customize the final drug product characteristics (e.g., multiple active ingredients, doses, flavor, viscosity, etc.) to meet individual patient/consumer needs and/or preferences while assuring high quality. Permitted combinations may be maintained in a database to enable networked drug product selection, prescribing, and ordering. Each resulting customized drug product dose can be labeled to facilitate compliance and reduce the number of drug products administered per day.
INTRODUCTION: Acute febrile illness (AFI), traditionally attributed to malaria, is a common reason for seeking primary healthcare in rural South and Southeast Asia. However, malaria transmission has declined while health workers are often poorly equipped to manage non-malarial AFIs. This results in indiscriminate antibiotic prescribing and care escalation, which promotes antibiotic resistance and may increase healthcare costs. To address this problem, an electronic clinical decision support algorithm (eCDSA) called 'Electronic clinical Decision support for Acute fever Management (EDAM)' has been developed for primary health workers which integrates clinical, epidemiological and vital sign data with simple point-of-care tests to produce a diagnosis and management plan.
METHODS AND ANALYSIS: This is a pragmatic cluster-randomised trial aiming to assess the effect of EDAM and related training on antibiotic prescribing rates in rural Cambodian primary health centres (PHCs) as the primary outcome, along with a range of secondary outcomes including safety. Patients with AFI are eligible for recruitment if they are aged ≥1 year. A cluster is defined as a PHC and PHCs will be randomised to control (standard of care) and intervention (EDAM and associated training) arms, with 15 PHCs per arm. Patients will be followed up after 7 days to ascertain the safety profile of EDAM. Each PHC will recruit 152 patients (total 4560), based on a baseline antibiotic prescription rate of 25% and expected reduction to 17.5% with EDAM.
ETHICS AND DISSEMINATION: Results will be published in international peer-reviewed journals to inform the design of future versions of EDAM and of future trials of similar eCDSAs and other digital health interventions targeted towards rural populations. This study was approved by the Oxford University Tropical Research Ethics Committee (550-23) and the Cambodian National Ethics Committee for Health Research (395-NECHR).
TRIAL REGISTRATION NUMBER: International Standard Randomized Controlled Trial Number Registry (ISRCTN15157105).
Brucella infections are mainly caused by smooth strains; however, Brucella canis with a rough morphology is able to infect humans. From domestic animals, the dog is the animal more closely related to its owner; as a result the contact of the dog with the members of the family is higher, thus increasing the possibility of infection. There are differences between the virulence of smooth and rough brucella, which are not given by the LPS; for instance, the secretion system type IV, which contributes to the virulence of the smooth species of Brucella. The survival of rough Brucella and their capability for causing disease is of interest, the activity study of the virB locus in these organisms is important, since it is one of the main elements of virulence identified and represents a potential target for immune and therapeutic response mechanisms. Mutant strains were generated in this operon, where the capacity of infection and replication in a cell model was analysed. The B canis VirB mut ants are non-virulent strains, which immunogenic characteristics were evaluated for finally estimating the capacity thereof for acting as a vaccine candidate in an animal model. The Brucella canis VirB10 and AvirB11:Gm mutant strains conferred in mice a solid humoral and cellular immune response, and had a short residual virulence. The VirB10 protected, before the experimental challenge, the 100% of mice and the AvirB11::Gm protected the 93.75% of the mice.
IMPORTANCE AND OBJECTIVES: Sleep disturbance is one of the most common and debilitating symptoms experienced by women during the menopause transition. However, there are currently no therapies specifically approved for sleep disturbance associated with the menopause. Here, we consider how to characterize sleep disturbance associated with the menopause and discuss its etiology, including the latest advances in our understanding of the neuronal circuits that regulate reproduction, body temperature, sleep, and mood; and reflect on its impact on women's health and well-being. We also examine the current treatment landscape and look to the future of treatment for this condition.
METHODS: We conducted a review of the literature and combined this with discussion with experts in the fields of sleep and menopause as well as experiences from our own clinical practices.
DISCUSSION AND CONCLUSIONS: Sleep disturbance associated with the menopause is characterized by frequent night-time awakenings and increased awake time after sleep onset. Its impacts are wide-ranging, negatively affecting health as well as personal and social relationships, productivity, and work performance. There is currently an unmet need for effective, safe, and well-tolerated treatments to address this important symptom, and wider recognition of the association between sleep disturbances and the menopause is needed. Sleep disturbances associated with the menopause can result from hormone changes as well as vasomotor and mood symptoms. Growing research has contributed to our knowledge of the role of hypothalamic estrogen-sensitive kisspeptin/neurokinin B/dynorphin neurons. These neurons are thought to integrate the gonadotropin-releasing hormone pathway and the pathways responsible for the homeostatic control of body temperature and the circadian regulation of sleep-wake cycles. Understanding these neurons offers the potential to create treatments that target a key cause of sleep disturbance associated with the menopause. Further research to understand their etiology and characterize the neuronal circuits responsible could benefit the development of these targeted treatment approaches.
A system is provided for aggregating user generated electronic data associated with a user from a plurality of computing machines located separately without user intervention. Metadata associated with the user generated electronic data is stored in an electronic record repository database to perform natural language processing and metadata analysis of the user generated electronic data to identify user verified data and user unverified data. A data object including query statements and approval options is generated and presented on a remotely located display unit accessible by the user. An input against each of the plurality of query statements is received. The system updates the unverified data based on the received input. The user generated electronic data is then pushed into the electronic transactional system which may communicate electronic data messages among a plurality of computer stations.
The rise in life expectancy has significantly increased the occurrence of age-related chronic diseases, leading to escalating expenses for both society and individuals. Among the main factors influencing health and lifespan, lifestyle takes a forefront position. Specifically, nutrition, mental activity, and physical exercise influence the molecular and functional mechanisms that contribute to the prevention of major age-related diseases. Gaining deeper insights into the mechanisms that drive the positive effects of healthy lifestyles is valuable for creating interventions to prevent or postpone the development of chronic degenerative diseases. This review summarizes the main mechanisms that underlie the positive effect of lifestyle factors in counteracting the major age-related diseases involving brain health, musculoskeletal function, cancer, frailty, and cardiovascular diseases, among others. This knowledge will help to identify high-risk populations for targeted intervention trials and discover new biomarkers associated with healthy aging.
PURPOSE: Optic nerve head (ONH) atrophy is frequently associated with hydrocephalic conditions. Cerebrospinal fluid (CSF)-containing meninges form a subarachnoid space that terminates at the ONH, which physically impacts it. This study aims to characterize optic neuropathy in congenital hydrocephalic mice with genetic disruption of the Ccdc13 gene.
METHODS: The ccdc13 germline knockout mice were generated. The hydrocephalus phenotype and subarachnoid space surrounding the optic nerve were evaluated using routine histology and Evans blue stain. Optic neuropathy was examined with immunohistochemistry and transmission electron microscopy (TEM). Axon transport was indicated by cholera toxin subunit B (CTB) fluorescence conjugate. Retinal function was evaluated by electroretinography (ERG), and Ccdc13 expression was revealed by a knock-in Gfp reporter.
RESULTS: Ccdc13 mutant mice manifested hydrocephalus at birth. ONH displacement, or negative cupping, and enlarged subarachnoid space at the optic terminus occurred as early as 1 month after birth. Intraocular pressure (IOP) was normal. Optic neuropathy was first observed at the ONH, followed by a distal-to-proximal progression of optic nerve pathology indicated by alteration of axonal ultrastructure and deposition of unphosphorylated neurofilament heavy chain. Anterograde axonal transport was also hampered. Retinal ganglion cell (RGC) function was compromised as early as postnatal day 21 (P21), along with reduced neurofilament heavy chain expression. Optic neuropathy caused by disruption of Ccd13 was non-cell autonomous, stemming from hydrocephalus with presumed high intracranial pressure (ICP), which physically impacts the ONH by increasing the translaminar pressure gradient.
CONCLUSIONS: We provided knowledge of optic neuropathy from a congenital mouse model for hydrocephalus. The hydrocephalus in mice could damage the ONH by increasing the translaminar pressure gradient and negative cupping, leading to impairment in axoplasmic transport and RGC pathology. Our findings highlight the importance of the interplay between IOP and ICP in the development of glaucoma.
Right ventricular pacing (RVP) is the standard treatment for patients with continuous ventricular pacing needs. However, clinical studies have shown that RVP can cause electrical and mechanical dyssynchrony of the left ventricle and increase the risks of cardiac insufficiency, atrial fibrillation (AF) and death. Although emerging evidence demonstrated that left bundle branch pacing (LBBP) is a promising alternative for patients with either a bradycardia or a heart failure pacing indication. However, a direct comparison of the safety, efficacy and LV systolic synchrony between LBBP and RVP regimens was rare. In this study, the investigators aim to conduct a comparison of the safety and effectiveness performance between these two pacing methods for patients with atrioventricular block (AVB). The investigators focused on AVB patients undergoing permanent pacemaker implantations from the 1st of January 2018 to the 18th of November 2021 at West China Hospital.
Significance: Chronic limb threatening ischemia (CLTI) is a severe form of peripheral arterial disease (PAD) that is associated with high rates of morbidity and mortality, and especially limb loss. In patients with no options for revascularization, stem cell therapy is a promising treatment option. Recent Advances: Cell therapy directly delivered to the affected ischemic limb has been shown to be a safe, effective, and feasible therapeutic alternative for patients with severe PAD. Multiple methods for cell delivery, including local, regional, and combination approaches, have been examined in both pre-clinical studies and clinical trials. This review focuses on delivery modalities used in clinical trials that deliver cell therapy to patients with severe PAD. Critical Issues: Patients with CLTI are at high risk for complications of the disease, such as amputations, leading to a poor quality of life. Many of these patients do not have viable options for revascularization using traditional interventional or surgical methods. Clinical trials have shown therapeutic benefit for cell therapy in these patients, but methods of cell treatment are not standardized, including the method of cell delivery to the ischemic limb. Future Directions: The ideal delivery approach for stem cell therapy in PAD patients remains unclear. Further studies are needed to determine the best modality of cell delivery to maximize clinical benefits.
Breast cancer survivors often self-report cognitive deficits, primarily in executive functioning (planning, problem solving, multitasking), memory, and processing speed after cancer treatment, i.e., cancer-related cognitive impairment (CRCI). The prevalence of CRCI following breast cancer is as high as 78% and can persist chronically after treatment has ended. In other health conditions associated with cognitive impairment, such as traumatic brain injury, the only evidence-based recommended practice standard for deficits in executive function is metacognitive strategy training (MCST). In this approach, participants are taught a general cognitive strategy that can be applied in known and novel contexts to devise task specific strategies to successfully engage in an activity. While the cognitive deficits identified in and described by breast cancer survivors seem quite amenable to MCST, there is no study in the published literature which measures the efficacy of MCST on CRCI. The Cognitive Orientation to daily Occupational Performance (CO-OP) approach is a MCST intervention in which subjects are taught a general cognitive strategy that can be applied in known and novel contexts to devise task specific strategies to engage in an activity. Preliminary data suggest that CO-OP may have a positive impact on subjective and objective cognitive performance in breast cancer survivors with CRCI. Further, this study will evaluate the neurophysiological underpinnings associated with treatment changes through the use of neuroimaging methods.
An herbal formulation employing a plurality of ingredients extracted from a plurality of herbs for the regeneration of cardiomyocytes by reducing the after effects of myocardial infarction is disclosed. the herbal formulation made from one or all of the ingredients include Terminalia arjuna, Pashanbhedi (F3ergenialingulata), Jatamansi (Nardostachysjatainansi), Swarnabhasma (gold ultra fine powder), Gandhakrasayan, Trifala (Myrabilis), Commiphoramukul, Triphala (three myrobalans) andcalcined pearl shell powder (Mukthapisthi) in appropriate percentage by weight of the conipoisition. According to the method of preparing the herbal formulation. the ingredients are purified by liquid solvent extraction and homogenization of herbal ingredients is achieved to attain a homogenous fortnulation. The .fonnulation is prepared in any of the forms include but not limited to a gelatin capsule. a vegetarian capsule, a tablet, a liquid, a syrup, a dairy beverage and a snack bar.
Counting the first day of menstruation as "Day 1", tablets are taken without interruption as follows: One dark blue tablet daily for 21 days, one white (inert) tablet daily for 2 days followed by 1 green (ethinyl estradiol) tablet daily for 5 days. For all subsequent cycles, the patient then begins a new 28-tablet regimen on the next day after taking the last green tablet. [If switching directly from another oral contraceptive, the first dark blue tablet should be taken on the first day of menstruation which begins after the last ACTIVE tablet of the previous product.]

If a patient misses 1 dark blue tablet, she should take the missed tablet as soon as she remembers. If the patient misses 2 consecutive dark blue tablets in Week 1 or Week 2, the patient should take 2 tablets the day she remembers and 2 tablets the next day; thereafter, the patient should resume taking 1 tablet daily until she finishes the cycle pack. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills. If the patient misses 2 consecutive dark blue tablets in the third week or if the patient misses 3 or more dark blue tablets in a row at any time during the cycle, the patient should throw out the rest of that cycle pack and start a new cycle pack that same day. The patient should be instructed to use a back-up method of birth control if she has intercourse in the 7 days after missing pills.
A composition for intracellular delivery of a chemical agent into an interleukin-2-receptor-bearing cell, e.g. an activated T cell, includes a chemical agent and at least two copies of an interleukin-2-receptor-binding and endocytosis-inducing ligand coupled to a water soluble polymer. The ligand binds to a receptor on the interleukin-2-receptor-bearing cell and elicits endocytosis of the composition. The composition also optionally includes a spacer for coupling the chemical agent and the ligand to the polymer. Chemical agents can include cytotoxins, transforming nucleic acids, gene regulators, labels, antigens, drugs, and the like. A preferred water soluble polymer is polyalkylene oxide, such as polyethylene glycol and polyethylene oxide, and activated derivatives thereof. The composition can further comprise a carrier such as another water soluble polymer, liposome, or particulate. Methods of using these compositions for delivering a chemical agent in vivo or in vitro are also disclosed.
The two euglycemic clamp studies described below [see Clinical Pharmacology (12.3)] assessed glucose utilization after dosing of healthy volunteers. NovoLog Mix 70/30 has an earlier onset of action than human premix 70/30 in studies of normal volunteers and patients with diabetes. The onset of action is between 10-20 minutes for NovoLog Mix 70/30 compared to 30 minutes for Novolin 70/30. The mean ± SD time to peak activity for NovoLog Mix 70/30 is 2.4 hr ± 0.8hr compared to 4.2 hr ± 0.4 hr for Novolin 70/30. The duration of action may be as long as 24 hours (see Figure 2).

Figure 2. Pharmacodynamic Activity Profile of NovoLog Mix 70/30 and Novolin 70/30 in healthy subjects.