anthonyyazdaniml/gliner-biomed-curated-corpus huggingface dataset:
Administration of enalapril maleate to patients with hypertension of severity ranging from mild to severe results in a reduction of both supine and standing blood pressure usually with no orthostatic component. Symptomatic postural hypotension is therefore infrequent, although it might be anticipated in volume-depleted patients (see WARNINGS).

In most patients studied, after oral administration of a single dose of enalapril, onset of antihypertensive activity was seen at one hour with peak reduction of blood pressure achieved by four to six hours.

At recommended doses, antihypertensive effects have been maintained for at least 24 hours. In some patients the effects may diminish toward the end of the dosing interval (see DOSAGE AND ADMINISTRATION).

In some patients achievement of optimal blood pressure reduction may require several weeks of therapy.

The antihypertensive effects of enalapril maleate have continued during long-term therapy. Abrupt withdrawal of enalapril maleate has not been associated with a rapid increase in blood pressure.

In hemodynamic studies in patients with essential hypertension, blood pressure reduction was accompanied by a reduction in peripheral arterial resistance with an increase in cardiac output and little or no change in heart rate. Following administration of enalapril maleate, there is an increase in renal blood flow; glomerular filtration rate is usually unchanged. The effects appear to be similar in patients with renovascular hypertension.

When given together with thiazide-type diuretics, the blood pressure lowering effects of enalapril maleate are approximately additive.

In a clinical pharmacology study, indomethacin or sulindac was administered to hypertensive patients receiving enalapril maleate. In this study there was no evidence of a blunting of the antihypertensive action of enalapril maleate (see PRECAUTIONS, Drug Interactions).
Participants will receive a single dose of cefiderocol administered intravenously (IV) on Day 1, in addition to standard of care. Participants weighing less than 34 kilograms (kg) will receive 60 milligrams (mg)/kg of cefiderocol and participants ≥34 kg will receive 2000 mg.
The ability of the Auditory Verbal Learning Test (AVLT) to lateralize hippocampal sclerosis (HS) in mesial temporal lobe epilepsy (MTLE) was explored in a sample of 50 patients with MTLE-HS (23 right and 27 left). Patients' AVLT scores were adjusted to the demographic characteristics of each individual in accordance with the Portuguese normative data. The laterality of the HS was determined by consensus by two neuroradiologists. ROC curves were used to identify the best AVLT cutoff scores to differentiate right vs. left HS. Diagnostic statistics were applied to different AVLT measures. The study results revealed that four AVLT scores can correctly classify the laterality of HS in the total sample and a sub-group of 39 right-handed patients (Edinburgh Laterality Inventory +100): delayed recall trial (76 and 80%, respectively), delayed recognition trial (64 and 67%, respectively), learning over trials index (64 and 74%, respectively), and long-term percent retention index (68 and 72%, respectively). In right-handed patients, the diagnostic capability of the delayed recall trial was improved by pairing it with the learning over trials index (accuracy of 85%). In sum, AVLT measures of verbal memory differentiate left from right HS in MTLE. The delayed recall trial demonstrated good diagnostic capacity.
A composition useful for maintaining healthy levels of testosterone in men and women. The composition includes essential oils from a tree of the genus  Picea  or a product of this oil. The essential oil product can specifically come from essential oil from the plant  Picea pungen s, commonly referred to as Blue Spruce. Also disclosed is a method for maintaining healthy levels of testosterone in men and women utilizing the composition. In some implementations, the composition is a pharmaceutical composition that further includes a penetration enhancer. A method for utilizing the pharmaceutical composition for treating hypogonadism is also disclosed.
Glutaraldehyde is a useful anti-microbial agent, but is dangerous and unpleasant to handle and is thermally unstable. Despite these disadvantages, it is specified for use against bacteria in cooling towers of air conditioning plants of buildings and to control anaerobic sulphate-reducing bacteria in oil wells. The invention provides the bisulphite addition complex of an aldehyde or di-aldehyde, for use as an anti-microbial agent. The complex is less toxic than free glutaraldehyde. In cooling towers it slowly oxidises to the free di-aldehyde. In oil wells, its digestion by the sulphate-reducing bacteria releases the free di-aldehyde which controls the bacteria. In these ways, a more economic and environmentally safer use of anti-microbial additives is likely
INTRODUCTION: Noncompressible torso hemorrhage (NCTH) accounts for most potentially survivable deaths on the battlefield. Treatment of NCTH is challenging, especially in far-forward environments with limited capabilities. Resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown promise in the care of patients with NCTH. REBOA involves introducing a balloon catheter into the descending aorta in a specific occlusion region (zones 1, 2, or 3) and acts as a hemorrhage control adjunct with resuscitative support. The balloon is placed in zone 3 in the infrarenal aorta for high junctional or pelvic injuries and in zone 1 proximal to the diaphragm for torso hemorrhage. Zone 1 REBOA provides more resuscitative support than zone 3; however, the potential for ischemia and reperfusion injuries is greater with zone 1 than with zone 3 REBOA placement. This study aims to determine the possible benefit of transitioning the REBOA balloon from zone 3 to zone 1 to rescue a patient with ongoing venous bleeding and impending cardiovascular collapse.
MATERIALS AND METHODS: Yorkshire male swine (70-90 kg, n = 6 per group) underwent injury to the femoral artery, which was allowed to bleed freely for 60 s, along with a simultaneous controlled venous hemorrhage. After 60 s, the arterial bleed was controlled with hemostatic gauze and zone 3 REBOA was inflated. Five hundred milliliters of Hextend was used for initial fluid resuscitation. The controlled venous bleed continued until a mean arterial pressure (MAP) of 30 mmHg was reached to create an impending cardiovascular collapse. The animals were then randomized into either continued zone 3 REBOA or transition from zone 3 to zone 1 REBOA. Following 30 min, a "hospital phase" was initiated, consisting of cessation of the venous hemorrhage, deflation of the REBOA balloon, and transfusion of one unit of whole blood administered along with saline and norepinephrine to maintain a MAP of 60 mmHg or higher. The animals then underwent a 2-h observation period. Survival, hemodynamics, and blood chemistries were compared between groups.
RESULTS: No significant differences between groups were observed in hemodynamic or laboratory values at baseline, postinitial injury, or when MAP reached 30 mmHg. Survival was significantly longer in animals that transitioned into zone 1 REBOA (log-rank analysis, P = .012). The average time of survival was 14 ± 10 min for zone 3 animals vs. 65 ± 59 min for zone 1 animals (P = .064). No animals in the zone 3 group survived to the hospital phase. Zone 1-treated animals showed immediate hemodynamic improvement after transition, with maximum blood pressure reaching near baseline values compared to those in the zone 3 group.
CONCLUSIONS: In this swine model of NCTH, hemodynamics and survival were improved when the REBOA balloon was transitioned from zone 3 to zone 1 during an impending cardiovascular collapse. Furthermore, these improved outcome data support the pursuit of additional research into mitigating ischemia-reperfusion insult to the abdominal viscera while still providing excellent resuscitative support, such as intermittent or partial REBOA.
Within 4 weeks of surgery, patients undergo radiation therapy and receive temozolomide PO over 42 days. Beginning 8 days prior to completion of chemoradiotherapy, patients receive plerixafor IV continuously for 2-4 weeks. Patients also receive temozolomide PO 5 days a month beginning 35 days after completion of radiation therapy.
Tertiary lymphoid organs (TLOs), also known as tertiary or ectopic lymphoid structures or tissues, are accumulations of lymphoid cells in sites other than canonical lymphoid organs, that arise through lymphoid neogenesis during chronic inflammation in autoimmunity, microbial infection, cancer, aging, and transplantation, the focus of this review. Lymph nodes and TLOs are compared regarding their cellular composition, organization, vascular components, and migratory signal regulation. These characteristics of posttransplant TLOs (PT-TLOs) are described with individual examples in a wide range of organs including heart, kidney, trachea, lung, artery, skin, leg, hand, and face, in many species including human, mouse, rat, and monkey. The requirements for induction and maintenance of TLOs include sustained exposure to autoantigens, alloantigens, tumor antigens, ischemic reperfusion, nephrotoxic agents, and aging. Several staging schemes have been put forth regarding their function in organ rejection. PT-TLOs most often are associated with organ rejection, but in some cases contribute to tolerance. The role of PT-TLOs in cancer is considered in the case of immunosuppression. Furthermore, TLOs can be associated with development of lymphomas. Challenges for PT-TLO research are considered regarding staging, imaging, and opportunities for their therapeutic manipulation to inhibit rejection and encourage tolerance.
Chronic kidney disease (CKD) is a significant global health issue and often involves CKD-mineral and bone disorder (MBD) and sarcopenia. Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. PAI-1 has been implicated in the pathogenesis of osteoporosis and muscle wasting induced by inflammatory conditions. However, the roles of PAI-1 in CKD-MBD and sarcopenia remain unknown. Therefore, the present study investigated the roles of PAI-1 in bone loss and muscle wasting induced by adenine in PAI-1-deficient mice. CKD was induced in PAI-1+/+ and PAI-1-/- mice by administration of adenine for ten weeks. Muscle wasting was assessed by grip strength test, quantitative computed tomography (CT) analysis and muscle weight measurement. Osteoporosis was assessed by micro-CT analysis of femoral microstructural parameters. PAI-1 deficiency did not affect adenine-induced decreases in body weight and food intake or renal dysfunction in male or female mice. PAI-1 deficiency also did not affect adenine-induced decreases in grip strength, muscle mass in the lower limbs, or the tissue weights of the gastrocnemius, soleus, and tibialis anterior muscles in male or female mice. PAI-1 deficiency aggravated trabecular bone loss in CKD-induced male mice, but significantly increased trabecular bone in CKD-induced female mice. On the other hand, PAI-1 deficiency did not affect cortical bone loss in CKD-induced mice. In conclusion, PAI-1 is not critical for the pathophysiology of CKD-MBD or CKD-induced sarcopenia in mice. However, PAI-1 may be partly related to bone metabolism in trabecular bone in the CKD state with sex differences.
Chronic airway inflammation induced by cigarette smoke (CS) plays an essential role in the pathogenesis of chronic obstructive pulmonary disease (COPD). MALAT1 is involved in a variety of inflammatory disorders. However, studies focusing on the interaction between MALAT1 and CS-induced airway inflammation remain unknown. The present study investigated the effects and mechanisms of MALAT1 in CS-induced airway inflammation in the pathogenesis of COPD. RT-qPCR was employed to determine the mRNA levels of MALAT1, miR-30a-5p and inflammatory cytokines. Protein concentrations of IL-1β and IL-6 in cell culture supernatant and mouse bronchoalveolar lavage fluid (BALF) were assessed by ELISA assay kits. Dual-luciferase reporter assay was conducted to verify the interaction between MALAT1 and miR-30a-5p. The protein expression of JNK and p-JNK was determined by western blot (WB). MALAT1 was highly expressed in cigarette smoke extract (CSE)-treated human bronchial epithelial cells (HBECs) and COPD mice lung tissues. Knockdown of MALAT1 significantly alleviate CS-induced inflammatory response. MALAT1 directly interacted with miR-30a-5p and knockdown of miR-30a-5p significantly inhibit the protective effects of MALAT1 silencing after CS exposure. Additionally, our results showed that miR-30a-5p could regulate inflammation via modulating the activation of JNK signaling pathway. Moreover, our results demonstrated MALAT1 could activate JNK signaling pathway by sponging miR-30a-5p. Our results demonstrated MALAT1 promotes CS-induced airway inflammation by inhibiting the activation of JNK signaling pathway via sponging miR-30a-5p.
All patients receive imatinib mesylate and hydroxyurea orally on a daily, continuous basis. Dosing of imatinib mesylate is adjusted for patients who are also receiving p450-inducing anti-epileptic drugs.
In dairy cows, the lactating mammary glands synthesize serotonin, which acts in an autocrine-paracrine manner in the glands and is secreted into the periphery. Serotonin signaling during lactation modulates nutrient metabolism in peripheral tissues such as adipose and liver. We hypothesized that the elevation of circulating serotonin during lactation would increase nutrient partitioning to the mammary glands, thereby promoting milk production. Our objective was to elevate circulating serotonin via intravenous infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP) to determine its effects on mammary supply and extraction efficiency of AA, and milk components production. Twenty-two multiparous mid-lactation Holstein cows were intravenously infused with 5-HTP (1 mg/kg body weight) or saline, in a crossover design with two 21-d periods. Treatments were infused via jugular catheters for 1 h/d, on d 1 to 3, 8 to 10, and 15 to 17 of each period, to maintain consistent elevation of peripheral serotonin throughout the period. Milk and blood samples were collected in the last 96 h of each period. Whole-blood serotonin concentration was elevated above saline control for 96 h after the last 5-HTP infusion. Dry matter intake was decreased for cows receiving 5-HTP, and on average they lost body weight over the 21-d period, in contrast to saline cows who gained body weight. Milk production and milk protein yield were lower in cows receiving 5-HTP during the 3 infusion days, but both recovered to saline cow yields in the days after. Although milk fat yield exhibited a day-by-treatment interaction, no significant difference occurred on any given day. Milk urea nitrogen concentration was lower in 5-HTP cows on the days following the end of infusions, but not different from saline cows on infusion days. Meanwhile, plasma urea nitrogen was not affected by 5-HTP infusion. Circulating concentrations of AA were overall transiently decreased by 5-HTP, with concentrations mostly returning to baseline within 7 h after the end of 5-HTP infusion. Mammary extraction efficiency of AA was unaffected by 5-HTP infusion. Overall, both lactation performance and circulating AA were transiently reduced in cows infused with 5-HTP, despite sustained elevation of circulating serotonin concentration.
Two randomized, open-label, clinical trials were conducted that evaluated the efficacy and safety of GENOTROPIN in Turner syndrome patients with short stature. Turner syndrome patients were treated with GENOTROPIN alone or GENOTROPIN plus adjunctive hormonal therapy (ethinylestradiol or oxandrolone). A total of 38 patients were treated with GENOTROPIN alone in the two studies. In Study 055, 22 patients were treated for 12 months, and in Study 092, 16 patients were treated for 12 months. Patients received GENOTROPIN at a dose between 0.13 to 0.33 mg/kg/week.

SDS for height velocity and height are expressed using either the Tanner (Study 055) or Sempé (Study 092) standards for age-matched normal children as well as the Ranke standard (both studies) for age-matched, untreated Turner syndrome patients. As seen in Table 6, height velocity SDS and height SDS values were smaller at baseline and after treatment with GENOTROPIN when the normative standards were utilized as opposed to the Turner syndrome standard.

Both studies demonstrated statistically significant increases from baseline in all of the linear growth variables (i.e., mean height velocity, height velocity SDS, and height SDS) after treatment with GENOTROPIN (see Table 6). The linear growth response was greater in Study 055 wherein patients were treated with a larger dose of GENOTROPIN.
BACKGROUND: Weight cycling is the repeated episodes manifesting intentional weight loss and subsequent unintentional weight gain. Whether the frequency and magnitude of weight cycling is associated with colorectal cancer risk independent of body mass index (BMI) remains unknown.
METHODS: Two prospective cohort studies, Nurses' Health Study I and Health Professionals Follow-up Study, followed 85,562 participants from 1992 to 2014. Participants completed a questionnaire regarding the frequency and magnitude of intentional weight loss in the past 4 years at the baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model.
RESULTS: We identified 1626 colorectal cancer cases during up to 22 years of follow-up. In the pooled analysis of HPFS and NHS, compared to non-weight cycling, moderate weight cycling (≥3 times of intentional weight loss of ≥2.3-4.4 kg) was associated with a reduced risk of colorectal cancer after adjustment for confounders, including attained BMI after weight cycling (HR = 0.82, 95% CI 0.69, 0.97). However, no significant association was observed in mild weight cyclers and in severe weight cyclers.
CONCLUSIONS: Moderate weight cycling was associated with a lower risk of colorectal cancer independent of BMI. This finding needs further studies for replication and putative biological mechanisms.
The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.
High-dose nebulized albuterol is standard therapy for severe asthma exacerbations at The Children's Hospital of Philadelphia (CHOP) and other tertiary care pediatric hospitals throughout the United States. For the most severe exacerbations, albuterol is provided continuously at high doses until improvement is observed. This regimen has been standardized in a treatment protocol that has been used at CHOP for more than 5 years. Recently, levalbuterol (LEV), the purified active (R)-enantiomer of albuterol, has been approved for use in acute asthma. Preliminary evidence suggests that LEV may improve pulmonary function and clinical outcomes in children with asthma based on studies using standard dosing regimens. Laboratory and clinical evidence suggest that the (S)-enantiomer of albuterol may have detrimental effects that contribute to poor response to racemic albuterol (RAC). Limited data exist about the efficacy of LEV in high-dose regimens.

This study will use a randomized, double-blind, controlled trial design in order to assess the safety and efficacy of LEV compared to RAC when delivered continuously in a high-dose regimen for severe exacerbations of asthma. Children treated for asthma exacerbations in the CHOP emergency department (ED) will be eligible for study enrollment. Those that meet enrollment criteria will be randomized to receive either high dose RAC according to the standard asthma care protocol or equivalent dosing of LEV. Approximately 128 patients with 64 in each arm of the study will be enrolled. An interim safety analysis will be conducted after the first 40 patients are enrolled. This study should be completed in six to nine months. The primary outcome will be duration of continuous therapy. Secondary outcomes will include improvement of clinical asthma score and change in forced expiratory volume in one second (FEV1). In addition, (R)-albuterol and (S)-albuterol levels will be measured at study entry and at 6-hour intervals in the first 40 patients enrolled. These values will be used to determine prior RAC exposure and to determine serum levels of (R) and (S) albuterol during continuous therapy.
BACKGROUND: Mitochondrial (MT) dysfunction is a hallmark of liver diseases. However, the effects of functional variants such as protein truncating variants (PTVs) in MT-related genes on the risk of liver diseases have not been extensively explored.
METHODS: We extracted 60,928 PTVs across 2466 MT-related nucleus genes using whole-exome sequencing data obtained from 442,603 participants in the UK Biobank. We examined their associations with liver dysfunction that represented by the liver-related biomarkers and the risks of chronic liver diseases and liver-related mortality.
RESULTS: 96.10% of the total participants carried at least one PTV. We identified 866 PTVs that were positively associated with liver dysfunction at the threshold of P value < 8.21e - 07. The coding genes of these PTVs were mainly enriched in pathways related to lipid, fatty acid, amino acid, and carbohydrate metabolisms. The 866 PTVs were presented in 1.07% (4721) of participants. Compared with participants who did not carry any of the PTVs, the carriers had a 5.33-fold (95% CI 4.15-6.85), 2.82-fold (1.69-4.72), and 4.41-fold (3.04-6.41) increased risk for fibrosis and cirrhosis of liver, liver cancer, and liver disease-related mortality, respectively. These adverse effects were consistent across subgroups based on age, sex, body mass index, smoking status, and presence of hypertension, diabetes, dyslipidemia, and metabolic syndrome.
CONCLUSIONS: Our findings revealed a significant impact of PTVs in MT-related genes on liver disease risk, highlighting the importance of these variants in identifying populations at risk of liver diseases and facilitating early clinical interventions.