anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Mechanism of Antiviral Action

Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV). The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. This viral enzyme converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. In vitro, acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase. The greater antiviral activity of acyclovir against HSV compared to VZV is due to its more efficient phosphorylation by the viral TK.

Antiviral Activities

The quantitative relationship between the in vitro susceptibility of herpes viruses to antivirals and the clinical response to therapy has not been established in humans, and virus sensitivity testing has not been standardized. Sensitivity testing results, expressed as the concentration of drug required to inhibit by 50% the growth of virus in cell culture (IC 50), vary greatly depending upon a number of factors. Using plaque-reduction assays, the IC50 against herpes simplex virus isolates ranges from 0.02 to 13.5 mcg/mL for HSV-1 and from 0.01 to 9.9 mcg/mL for HSV-2. The IC 50 for acyclovir against most laboratory strains and clinical isolates of VZV ranges from 0.12 to 10.8 mcg/mL. Acyclovir also demonstrates activity against the Oka vaccine strain of VZV with a mean IC 50 of 1.35 mcg/mL.

Drug Resistance

Resistance of HSV and VZV to acyclovir can result from qualitative and quantitative changes in the viral TK and/or DNA polymerase. Clinical isolates of HSV and VZV with reduced susceptibility to acyclovir have been recovered from immunocompromised patients, especially with advanced HIV infection. While most of the acyclovir-resistant mutants isolated thus far from immunocompromised patients have been found to be TK-deficient mutants, other mutants involving the viral TK gene (TK partial and TK altered) and DNA polymerase have been isolated. TK-negative mutants may cause severe disease in infants and immunocompromised adults. The possibility of viral resistance to acyclovir should be considered in patients who show poor clinical response during therapy.
Participants will receive up to 8 administrations of HSPPC-96 25 µg intradermally over 3 months (4 weekly doses, followed by 4 bi-weekly doses \[at Weeks 14, 15, 16, 17 19, 21, 23, and 25 in Part 1a and at Weeks 1-4, 6, 8, 10, 12 in Part 1b). Participants will remain untreated with HSPPC-96 for the initial 3-month period in Part 1a for immune monitoring blood draw.
Hyperkalemia will rarely occur in patients with adequate urinary output, but it is a possibility if large doses are used for considerable periods of time. If hyperkalemia is observed, Dyrenium (triamterene) should be withdrawn. The normal adult range of serum potassium is 3.5 to 5.0 mEq per liter, with 4.5 mEq often being used for a reference point. Potassium levels persistently above 6 mEq per liter require careful observation and treatment. Normal potassium levels tend to be higher in neonates (7.7 mEq per liter) than in adults. Serum potassium levels do not necessarily indicate true body potassium concentration. A rise in plasma pH may cause a decrease in plasma potassium concentration and an increase in the intracellular potassium concentration. Because Dyrenium conserves potassium, it has been theorized that in patients who have received intensive therapy or been given the drug for prolonged periods, a rebound kaliuresis could occur upon abrupt withdrawal. In such patients, withdrawal of Dyrenium should be gradual.
The safety of fentanyl transdermal system was evaluated in three open-label trials in 291 pediatric patients with chronic pain, 2 years of age through 18 years of age. Starting doses of 25 mcg/hr and higher were used by 181 patients who had been on prior daily opioid doses of at least 45 mg/day of oral morphine or an equianalgesic dose of another opioid. Initiation of fentanyl transdermal system therapy in pediatric patients taking less than 60 mg/day of oral morphine or an equianalgesic dose of another opioid has not been evaluated in controlled clinical trials. Approximately 90% of the total daily opioid requirement (fentanyl transdermal system plus rescue medication) was provided by fentanyl transdermal system.

Fentanyl transdermal system was not studied in children under 2 years of age.

Fentanyl transdermal system should be administered to children only if they are opioid-tolerant and 2 years of age or older (see DOSAGE AND ADMINISTRATION and BOX WARNING).

To guard against accidental ingestion by children, use caution when choosing the application site for fentanyl transdermal system (see DOSAGE AND ADMINISTRATION) and monitor adhesion of the system closely.
An osmotic delivery system has a membrane plug retention mechanism which can also be used to control the delivery rate of a beneficial agent from the osmotic delivery system. The osmotic delivery device includes an implant capsule containing a beneficial agent and an osmotic agent. Holes are formed along a side wall of the implant capsule at an open end of the capsule. When the membrane plug is inserted into the open end of the capsule the membrane material swells into the holes in the capsule side wall creating a large frictional force which prevents expulsion of the membrane plug. A beneficial agent delivery rate of the osmotic delivery system is controllable by varying the size and number of the holes to change the amount of exposed surface area of the membrane plug. An increase in the surface area of the membrane plug exposed to the exterior environment causes a corresponding increase in the liquid permeation rate of the membrane and thus, increases the beneficial agent delivery rate.
PURPOSE: Corrective long spinal fusion is a widely accepted surgical method for patients with adult spinal deformities. However, instrumented long fusion is associated with a significant risk of complications. Therefore, we aimed to assess the success of short-segment spinal fusion, particularly for bone marrow edema (BME) adjacent to the vertebral endplate, in patients with low back pain (LBP) and spinal deformity.
METHODS: A prospective study was performed at multiple hospitals wherein we monitored patients with spinal deformities and accompanying LBP. Patients aged ≥ 50 years with a minimum LBP severity score of 40 mm on the visual analog scale (VAS) were included in the study. We also included patients with lumbar BME on magnetic resonance imaging. Short spinal fusion was performed on segments with BME. Clinical evaluations of LBP on VAS and Oswestry Disability Index (ODI), and radiological parameters for sagittal vertical axis (SVA), pelvic incidence (PI), lumbar lordosis (LL) and pelvic tilt (PT) were carried out.
RESULTS: Overall, 35 patients (22 men and 13 women), with a mean age of 66.7 years and a mean follow-up period of 32 months, were included in the study. The mean VAS and ODI scores were 72.4 mm and 49.0% before surgery and 25.5 mm and 29.9% at the final follow-up, respectively; these parameters significantly improved after surgery. The SVA, PI-LL, and PT scores were 70.1 mm, 20.9°, and 22.8° before surgery and 85.4 mm, 13.8°, and 22.7° at the final follow-up, respectively. The spinal alignment parameters did not change significantly after surgery.
CONCLUSIONS: Short-segment spinal fusion is effective for treating LBP and spinal deformity with BME adjacent to the vertebral endplate without spinal correction.
A wait-listed control group of 71 Latinas will receive IA in the same manner as the intervention group. Latinas will start watching the telenovela episodes 7 months after their baseline survey (after T3 survey). Latinas will be informed at recruitment of this group condition and the study randomization. During the waiting time, participants will be called on a monthly basis to encourage participation and refer to services if needed.
Autoimmune cytopenias such as neutropenia (0.1%), hemolytic anemia (0.3%), and pancytopenia (0.2%) occurred in LEMTRADA-treated patients in MS clinical studies (controlled and open-label extension). In cases of autoimmune hemolytic anemia, patients tested positive for direct antiglobulin antibodies, and nadir hemoglobin levels ranged from 2.9–8.6 g/dL. Symptoms of autoimmune hemolytic anemia include weakness, chest pain, jaundice, dark urine, and tachycardia. One LEMTRADA-treated patient with autoimmune pancytopenia died from sepsis.

During postmarketing use, additional autoimmune cytopenias, including fatal autoimmune hemolytic anemia and aplastic anemia, have been reported in the treatment of patients with B-CLL, as well as other disorders, generally at higher and more frequent doses of alemtuzumab than recommended in MS.

Use CBC results to monitor for cytopenias. Prompt medical intervention is indicated if a cytopenia is confirmed.
FIELD: medicine, phytotherapy. SUBSTANCE: invention relates to agents prepared of medicinal plants and eliciting antiviral activity with regards to human immunodeficiency virus and pathogens of infections transferring by sexual way. Invention proposes agent comprising alpizarin, flakoside chelepin or chelepin D, eucalimine taken in the ratio = 1: 1: (2.0-3.0) : (0.4-0.5), respectively. Proposed components provide multiple pattern and polyfunctionality of complex for control of infections transferring by sexual way. EFFECT: valuable medicinal properties of complex. 3 tbl
The invention discloses an anti-asthmatic drug, and belongs to the field of research and development of new drugs. The immune balance of the body is regulated by an immune system through different cytokines such as TNF-alpha (tumor necrosis factor-alpha), IL-4 (interleukin-4), INF-gamma (interferon-gamma). By establishing an IL-4-GFP (green fluorescence protein) transgene, a high-throughput screening model and an asthma model of mice are reported, and small-molecule drugs which can inhibit the secretion of IL-4 are screened. A small molecule compound which can inhibit the secretion of IL-4 and has an anti-asthmatic effect is found and named as # 29, and is shown in a structural formula (I). After the combination of IL-4 and a receptor IL-4R of the IL-4, downstream signals are collected for transduction to activate effectors and activate the proliferation and differentiation of B cells and eosinophils. The production of excess IL-4 can be mediated and accelerate various diseases, so that the reduction in the content of the IL-4 is an effective treatment means of inflammation, infection, immune or malignant diseases such as asthma and psoriasis. The small-molecule drug can inhibit the expression of the IL-4, and thus is expected to be developed into the anti-asthmatic drug.
During the high salt intake period, patients received a 10-20 mmol sodium diet plus sodium tablets (180 mEq/die) to achieve a 200 mmol intake /day for two weeks. During the low salt intake period, patients received a 10-20 mmol sodium diet + placebo tablets for two weeks.
The gut-immune axis is a relatively novel phenomenon that provides mechanistic links between the gut microbiome and the immune system. A growing body of evidence supports it is key in how the gut microbiome contributes to several diseases, including hypertension and cardiovascular diseases (CVDs). Evidence over the past decade supports a causal link of the gut microbiome in hypertension and its complications, including myocardial infarction, atherosclerosis, heart failure, and stroke. Perturbations in gut homeostasis such as dysbiosis (i.e., alterations in gut microbial composition) may trigger immune responses that lead to chronic low-grade inflammation and, ultimately, the development and progression of these conditions. This is unsurprising, as the gut harbors one of the largest numbers of immune cells in the body, yet is a phenomenon not entirely understood in the context of cardiometabolic disorders. In this review, we discuss the role of the gut microbiome, the immune system, and inflammation in the context of hypertension and CVD, and consolidate current evidence of this complex interplay, whilst highlighting gaps in the literature. We focus on diet as one of the major modulators of the gut microbiota, and explain key microbial-derived metabolites (e.g., short-chain fatty acids, trimethylamine N-oxide) as potential mediators of the communication between the gut and peripheral organs such as the heart, arteries, kidneys, and the brain via the immune system. Finally, we explore the dual role of both the gut microbiome and the immune system, and how they work together to not only contribute, but also mitigate hypertension and CVD.
Sex differences in the epidemiology and clinical characteristics of schizophrenia are well-known; however, the molecular mechanisms underlying these differences remain unclear. Further, the potential advantages of sex-stratified meta-analyses of epigenome-wide association studies (EWAS) of schizophrenia have not been investigated. Here, we performed sex-stratified EWAS meta-analyses to investigate whether sex stratification improves discovery, and to identify differentially methylated regions (DMRs) in schizophrenia. Peripheral blood-derived DNA methylation data from 1519 cases of schizophrenia (male n = 989, female n = 530) and 1723 controls (male n = 997, female n = 726) from three publicly available datasets, and the TOP cohort were meta-analyzed to compare sex-specific, sex-stratified, and sex-adjusted EWAS. The predictive power of each model was assessed by polymethylation score (PMS). The number of schizophrenia-associated differentially methylated positions identified was higher for the sex-stratified model than for the sex-adjusted one. We identified 20 schizophrenia-associated DMRs in the sex-stratified analysis. PMS from sex-stratified analysis outperformed that from sex-adjusted analysis in predicting schizophrenia. Notably, PMSs from the sex-stratified and female-only analyses, but not those from sex-adjusted or the male-only analyses, significantly predicted schizophrenia in males. The findings suggest that sex-stratified EWAS meta-analyses improve the identification of schizophrenia-associated epigenetic changes and highlight an interaction between sex and schizophrenia status on DNA methylation. Sex-specific DNA methylation may have potential implications for precision psychiatry and the development of stratified treatments for schizophrenia.
PROBLEM TO BE SOLVED: To prepare a fluoroxetine enteric pellet suitable for maintenance therapy without an increase in undesirable side effects by providing an enteric layer composed of a specific compound on a core containing fluoroxetine which is an anti-depressant drug. SOLUTION: This fluoroxetine enteric pellet is prepared by including (a) a core consisting of fluoroxetine and a pharmaceutically acceptable excipient and (b) an enteric layer comprising hydroxypropylmethylcellulose acetate succinate (hereinafter abbreviated to HPMCAS) and a pharmaceutically acceptable excipient. A separating layer is preferably provided between the core (a) and the enteric layer (b) and a finishing layer is preferably provided on the outside of the enteric layer (b). The HPMCAS in the enteric layer is preferably partially neutralized with ammonia, etc., to the degree that from 0 to about 15% of succinic groups are neutralized. Sugar (preferably sucrose) is preferably used as the separating layer. A formulation using the pellet (preferably a gelatin capsule) is effective against depression and further obsessive- compulsive disorder, bulimia, etc.
Technology-enhanced Group Tele-consultation. This consultation method requires that participants be prepared to review and receive feedback on audiorecorded CPT sessions in a group format. The CPT expert randomly selects two clinician sessions each week that have been audiorecorded to use for feedback and discussion in group teleconference based on procedures used in previous training initiatives (Stirman, Bhar, et al., 2010). Five- to twenty-minute segments of the two sessions will be shared within the group consultation. The CPT expert will provide feedback on the sessions with an emphasis on review of key learning points. These consultation group sessions will be facilitated with collaborative meeting software that includes audio file uploading.
BACKGROUND: Walking as a treatment is recommended for people with intermittent claudication (IC), but participation tends to be poor. Walking treatment beliefs, as defined by the Theory of Planned Behaviour (TPB) are associated with walking behavior, so assessing and designing interventions targeting walking treatment beliefs are crucial. To assess walking treatment beliefs in people with IC in Gujarat, a translated, culturally adapted questionnaire that assesses the four TPB constructs (attitude, subjective normative beliefs, perceived behavioral control beliefs, and intention to walk) is required.
AIM: To translate and cross-culturally assess the content validity and face validity of a Gujarati version of a TPB questionnaire that assesses walking treatment beliefs.
MATERIALS AND METHODS: A forward-backward translation of the 12-item TPB questionnaire was applied using a standardized approach. The translated versions were compared with the original questionnaire, and ten experts, rated each item according to: clarity, semantic, appropriateness, and cultural relevance. Content Validity Index (CVI), item level content validity (I-CVI), Scale -content validity index (S-CVI/Ave), and universal agreement (UA) were computed to summarize the overall content validity of the questionnaire as well as a proportion of agreement with content experts. Face validity was assessed using a think-aloud approach with ten patients with IC. This cognitive interviewing approach (think-aloud approach) asked participants to describe their thoughts whilst completing the questionnaire. Responses were analyzed thematically.
RESULTS: There was complete agreement between experts for 9/12 items (I-CVI=1.00), leading to an overall agreement (S-CVI/Ave) of 0.98. For face validation, at least 50% of the participants had no significant problems with any question in the questionnaire. Most problems participants encountered were straightforward, such as re-reading some questions or considering the questions carefully before answering.
CONCLUSION: The Gujarati TPB questionnaire had excellent content validity and was comprehensible and answerable by the majority of our participants with IC and, therefore, had good face validity; this will enable walking treatment beliefs to be assessed in people with IC.
OBJECTIVE: To analyze the effectiveness and tolerability of various regimens for the use of tolperisone hydrochloride (TH) in the treatment of patients with acute nonspecific lower back pain (ALBP).
MATERIAL AND METHODS: 90 patients with ALBP (54.3 [48.7; 61.3] years) were divided into 2 groups: group 1 (n=45) received basic therapy - NSAIDs, B vitamins and TH sustained release (450 mg/day per os), group 2 (n=45) used basic treatment and TH 2 ml intramuscularly 2 times a day for 5 days with a transition to a TH sustained release 450 mg/day per os. The total duration of the study was 30 days. We analyzed the visual analogue pain scale (VAS-B), the results of the modified modified Schober test (MMST), the medication adherence scale (Drug Attitude Inventory - DAI-10), the Epworth daytime sleepiness scale (ESS), functional activity associated with low back pain (Roland-Maurice questionnaire, RM), duration of TH intake (days), frequency and characteristics of adverse events (AE). At the screening visit, all patients were additionally divided depending on the intensity of pain according to VAS-B («mild», «moderate», «severe»).
RESULTS: There were no significant differences on the VAS-B scale between groups 1 and 2 in patients with mild pain; there was significantly more complete pain control in group 2 with moderate pain after 14 and 30 days, (p=0.0013, 14 days; p=0.0021, 30 days); among patients with severe pain, the best result after 30 days was observed in group 2 (p=0.0016). In all patients the range of motion in the lumbosacral spine (MSST) significantly increased and functional activity (RM) improved compared to the initial state: more significant in group 2 with moderate pain after 14 and 30 days and with severe pain after 30 days. There was a high adherence to therapy (DAI-10), more pronounced in the first 14 days in patients of group 1. Excessive daytime sleepiness (ESS) was not observed. For moderate pain, patients in group 2 used TH for a significantly shorter period of time (16.4±1.6 days) compared to patients in group 1 (19.6±2.2 days, p=0.0022). AE were mild and did not serve as a reason to refuse therapy.
CONCLUSION: A protocol for prescribing TH was proposed, based on stratification of patients according to VAS-B.The use of TH for ALBP is effective and safe. The proposed protocol for stratifying patients according to VAS-B level allows identifying the patients with step-by-step scheme of prescribing the drug for a period of 14 to 30 days.
QTL-seq, linkage mapping, and whole-genome resequencing revealed a new locus (qCLS5.1) controlling Cercospora canescens resistance in mungbean and Receptor-like protein 12 (RLP12) genes as candidate genes for the resistance. Cercospora leaf spot (CLS) disease, caused by Cercospora canescens, is a common disease of mungbean (Vigna radiata). In this study, the genetics of CLS resistance was investigated in a new source of resistance (accession V2817) and the resistance was finely mapped to identify candidate genes. F2 and F2:3 populations of the cross V1197 (susceptible) × V2718 and a BC1F1 population of the cross V1197 × (V1197 × V2817) were used in this study. Segregation analysis suggested that the resistance is controlled by a single dominant gene. QTL-seq using F2 individuals revealed that a single QTL (designated qCLS5.1) on chromosome 5 controlled the resistance. The qCLS5.1 was confirmed in the F2:3 and BC1F1 populations by QTL analysis. Fine mapping using 978 F2 individuals localized qCLS5.1 to a 48.94 Kb region containing three tandemly duplicated Receptor-like protein 12 (RLP12) genes. Whole-genome resequencing and alignment of V1197 and V2817 revealed polymorphisms causing amino acid changes and premature stop codons in the three RLP12 genes. Collectively, these results show that qCLS5.1 is a new locus for CLS resistance in mungbean, and a cluster of RLP12 genes are candidate genes for the resistance. The new locus qCLS5.1 will be useful for molecular breeding of durable CLS-resistant mungbean cultivars.
Women with chronic kidney disease are less likely to become pregnant and are more susceptible to pregnancy complications when compared to patients with normal kidney function. As a result, these are considered high-risk pregnancies, both maternal and fetal. Over the years, there has been an increase in the incidence of pregnancies in dialysis patients, and an improvement in maternal and fetal outcomes. It is believed that the optimization of obstetric and neonatal care, the adjustment of dialysis treatment (particularly the increase in the number of hours and weekly frequency of dialysis sessions), and the use of erythropoiesis-stimulating agents have provided better metabolic, volume, blood pressure, electrolyte, and anemia control. This review article aims to analyze pregnancy outcomes in chronic kidney disease patients undergoing dialysis and to review nephrological medical management in this scenario. Due to the growing interest in the subject, clinical recommendations for care practice have become more consistent in both drug and dialysis management, aspects that are addressed in this review.