Miracle-dz/UniFAR-FTUs huggingface dataset:
The Grasshopper: A Novel Model for Assessing Vertebrate Brain Uptake

The aim of the present study was to develop a blood-brain barrier (BBB) permeability model that is applicable in the drug discovery phase. The BBB ensures proper neural function, but it restricts many drugs from entering the brain, and this complicates the development of new drugs against central nervous system diseases. Many in vitro models have been developed to predict BBB permeability, but the permeability characteristics of the human BBB are notoriously complex and hard to predict. Consequently, one single suitable BBB permeability screening model, which is generally applicable in the early drug discovery phase, does not yet exist. A new refined ex vivo insect-based BBB screening model that uses an intact, viable whole brain under controlled in vitro-like exposure conditions is presented. This model uses intact brains from desert locusts, which are placed in a well containing the compound solubilized in an insect buffer. After a limited time, the brain is removed and the compound concentration in the brain is measured by conventional liquid chromatography-mass spectrometry. The data presented here include 25 known drugs, and the data show that the ex vivo insect model can be used to measure the brain uptake over the hemolymph-brain barrier of drugs and that the brain uptake shows linear correlation with in situ perfusion data obtained in vertebrates. Moreover, this study shows that the insect ex vivo model is able to identify P-glycoprotein (Pgp) substrates, and the model allows differentiation between low-permeability compounds and compounds that are Pgp substrates.
Effects of Sitagliptin on Glycemia, Incretin Hormones, and Antropyloroduodenal Motility in Response to Intraduodenal Glucose Infusion in Healthy Lean and Obese Humans and Patients With Type 2 Diabetes Treated With or Without Metformin

The impact of variations in gastric emptying, which influence the magnitude of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) secretion, on glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors is unclear. We evaluated responses to intraduodenal glucose infusion (60 g over 120 min [i.e., 2 kcal/min], a rate that predominantly stimulates GIP but not GLP-1) after sitagliptin versus control in 12 healthy lean, 12 obese, and 12 type 2 diabetic subjects taking metformin 850 mg b.i. d. versus placebo. As expected, sitagliptin augmented plasma-intact GIP substantially and intact GLP-1 modestly. Sitagliptin attenuated glycemic excursions in healthy lean and obese but not type 2 diabetic subjects, without affecting glucagon or energy intake. In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin. These observations indicate that in type 2 diabetes, 1) the capacity of endogenous GIP to lower blood glucose is impaired; 2) the effect of DPP-4 inhibition on glycemia is likely to depend on adequate endogenous GLP-1 release, requiring gastric emptying >2 kcal/min; and 3) the action of metformin to lower blood glucose is not predominantly by way of the incretin axis.
How useful are bone turnover markers in rheumatoid arthritis? Influence of disease activity and corticosteroid therapy.

UNLABELLED Rheumatoid arthritis is associated with osteopenia possibly related to increased bone resorption. Until recently, the markers used to evaluate bone turnover lacked specificity, and as a result studies were difficult to interpret. OBJECTIVES To study bone remodeling in patients with rheumatoid arthritis, with special attention to the effects of corticosteroid therapy. PATIENTS AND METHODS Forty-eight patients (36 women and 12 men) with a mean age of 54.6 +/- 11.6 years and a mean disease duration of 11 +/- 9 years were studied. Thirty-nine patients (81%) had positive tests for rheumatoid factors, and 21 (43.7%) were under corticosteroid therapy, with a mean treatment duration of 4.5 +/- 2.9 years and a mean daily dosage of 9.4 +/- 2.5 mg prednisone. A group of age- and sex-matched controls was also studied. Serum levels of procollagen Type I C-terminal propeptide (PINP), procollagen Type I N-terminal propeptide (PINP), and procollagen type I C-terminal telopeptide (ICTP) were determined in all patients and controls. The first two markers reflect bone formation and the last bone resorption. Other tests performed in each patient were the erythrocyte sedimentation rate, serum C-reactive protein, serum total alkaline phosphatase, serum osteocalcin, 24-hour urinary hydroxyproline excretion, and calcium/creatinine ratio in a morning urine sample. Several clinical parameters were used to evaluate disease activity and severity in the rheumatoid arthritis patients. RESULTS ICTP levels were significantly elevated in the patients as compared with the controls (6.6 +/- 3.9 ng/ml versus 3.1 +/- 1.2 ng/ml, P = 0.0001), whereas no significant differences were found for PICP or PINP. Similar results were found when the analysis was confined to nonsteroid-medicated patients. Conversely, PICP levels were higher in steroid-medicated patients than in controls (P = 0.0132) and were correlated with steroid therapy duration (r = 0.436). ICTP levels were correlated with age (r = 0.3), Lee's index (r = 0.585), the Health Assessment Questionnaire score (r = 0.391), and the erythrocyte sedimentation rate (r = 0.442). Urinary hydroxyproline excretion was elevated in 41.6% of the patients. CONCLUSION Our data suggest that rheumatoid arthritis is associated with increased bone resorption, and that steroid therapy further accelerates bone remodeling in this disease.
Role of Ultrasound in Dengue Infection

Dengue has become a major national and international public health concern in recent years. Though for all practical purposes serology of dengue virus remains the gold standard in diagnosing the disease, ultrasound abdomen can detect early signs of the disease. Our study was performed to highlight and demonstrate ultrasound findings of dengue fever, assess efficacy USG findings, suspect and predict the progression of mild dengue fever to severe dengue fever by USG and its complications, thus helping in further management of patients with dengue fever. Total 200 patients with complaints and clinical findings pertaining to Dengue fever (dengue positive by IgM MAC ELISA) are evaluated by Toshiba’s Xario USG machine in our department. Mean age of presentation was-22.45 years and 15, 26 years for females and males respectively. There was significant statistical difference noted between mild and severe cases of dengue fever related to sonological variables like ascites, pleural effusion, and perinephric edema. Ultrasound abdomen is useful for early prediction of the severity of dengue fever, thus helps in triage and prevention of those cases which will further progress to dengue haemorrhagic fever or dengue shock syndrome.
Micronuclei in Peripheral Blood and Bone Marrow Cells of Mice Exposed to 42 GHz Electromagnetic Millimeter Waves

Abstract Vijayalaxmi, Logani, M. K. , Bhanushali, A. , Ziskin, M. C. and Prihoda, T. J. Micronuclei in Peripheral Blood and Bone Marrow Cells of Mice Exposed to 42 GHz Electromagnetic Millimeter Waves. Radiat. Res. 161, 341–345 (2004). The genotoxic potential of 42.2 ± 0.2 GHz electromagnetic millimeter-wave radiation was investigated in adult male BALB/c mice. The radiation was applied to the nasal region of the mice for 30 min/day for 3 consecutive days. The incident power density used was 31.5 ± 5.0 mW/cm2. The peak specific absorption rate was calculated as 622 ± 100 W/kg. Groups of mice that were injected with cyclophosphamide (15 mg/kg body weight), a drug used in the treatment of human malignancies, were also included to determine if millimeter-wave radiation exposure had any influence on drug-induced genotoxicity. Concurrent sham-exposed and untreated mice were used as controls. The extent of genotoxicity was assessed from the incidence of micronuclei in polychromatic erythrocytes of peripheral blood and bone marrow cells collected 24 h after treatment. The results indicated that the incidence of micronuclei in 2000 polychromatic erythrocytes was not significantly different among untreated, millimeter wave-exposed, and sham-exposed mice. The group mean incidences were 6.0 ± 1.6, 5.1 ± 1.5 and 5.1 ± 1.3 in peripheral blood and 9.1 ± 1.1, 9.3 ± 1.6 and 9.1 ± 1.6 in bone marrow cells, respectively. Mice that were injected with cyclophosphamide exhibited significantly increased numbers of micronuclei, 14.6 ± 2.7 in peripheral blood and 21.3 ± 3.9 in bone marrow cells (P< 0.0001). The drug-induced micronuclei were not significantly different in millimeter wave-exposed and sham-exposed mice; the mean incidences were 14.3 ± 2.8 and 15.4 ± 3.0 in peripheral blood and 23.5 ± 2.3 and 22.1 ± 2.5 in bone marrow cells, respectively. Thus there was no evidence for the induction of genotoxicity in the peripheral blood and bone marrow cells of mice exposed to electromagnetic millimeter-wave radiation. Also, millimeter-wave radiation exposure did not influence cyclophosphamide-induced micronuclei in either type of cells.
Hyperhomocysteinemia in rheumatoid arthritis: influence of methotrexate treatment and folic acid supplementation.

OBJECTIVE To examine the effect of methotrexate (MTX) and folic acid supplementation on the homocysteine level in patients with rheumatoid arthritis (RA). METHODS A cross sectional study was performed in 81 patients with RA, comprising a standardized clinical interview, an examination, and a blood specimen test. RESULTS P-homocysteine tended to be lower in 41 patients receiving MTX, compared with 40 patients not receiving MTX. Of the MTX treated patients, 76% received folic acid supplementation. Multivariate analysis revealed a statistically significant association between P-homocysteine and P-creatinine (p < 0.001), and disease activity/progression measured by the Health Assessment Questionnaire score (p < 0.001). There was a tendency to negative association between P-homocys-teine and folic acid supplementation. CONCLUSION P-homocysteine in patients with RA receiving MTX and folic acid supplementation did not differ significantly from P-homocysteine in RA patients receiving other types of treatment.
Children's judgements of correct and reversed sentences with ‘if’

ABSTRACT Judgements of grammatical acceptability were made for correct and reversed ‘Y if X’ and ‘If X, Y’ sentences. Children aged 4; 10–8; 7 judged sentences ‘sensible’ or ‘silly’ and modified the sentences to make them ‘silly’ or ‘sensible’. Children failed to differentiate correct and reversed-order sentences prior to age 7 or 8. There was no evidence of an order-of-mention response strategy, but ‘If X, Y’ and ‘If Y, X’ sentences were easier to judge than ‘Y if X’ and ‘X if Y’, suggesting that children prefer sentences in which stated order parallels temporal order. The strategies used to modify the sentences changed with age from content changes to order reversals. The modifications suggested that contingency becomes a component of the meaning of if before the child assigns unidirectional event order as a component of if.
Children, adolescents, and television.

In 1984 the American Academy of Pediatrics (AAP) issued a statement that cautioned pediatricians and parents about the potential for television to promote violent or aggressive behavior and obesity.1 The influence of television on early sexual activity, drug and alcohol use and abuse, school performance, and perpetuation of ethnic stereotypes was also stressed. In 1990, the AAP reaffirmed its concerns about the negative effects of television on children and adolescents and provided recommendations to pediatricians and parents for prevention and management of these effects.2 In 1993, most children in the United States still spent more time (outside of school hours) watching television than performing any other activity except sleeping. According to recent Nielsen data,3 the average child and adolescent watches television between 21 and 23 hours per week, with the youngest children viewing the most hours per week. Although the amount of commercial television viewed by children has declined since 1980, the most recent estimates of television viewing do not include the use of videocassette recorders. Therefore, the amount of time that children in our country spend in front of the television set has probably not decreased significantly in the past decade. Television's influence on children is a function of the length of time they spend watching and the cumulative effect of what they see. By the time the average child reaches age 70, he or she will have spent approximately 7 to 10 years watching television.4 Therefore, the passive nature of television may displace other more active and meaningful experiences of the world.
Meisoindigo, but not its core chemical structure indirubin, inhibits zebrafish interstitial leukocyte chemotactic migration

Abstract Context: Inflammatory disease is a big threat to human health. Leukocyte chemotactic migration is required for efficient inflammatory response. Inhibition of leukocyte chemotactic migration to the inflammatory site has been shown to provide therapeutic targets for treating inflammatory diseases. Objective: Our study was designed to discover effective and safe compounds that can inhibit leukocyte chemotactic migration, thus providing possible novel therapeutic strategy for treating inflammatory diseases. Materials and methods: In this study, we used transgenic zebrafish model (Tg:zlyz-EGFP line) to visualize the process of leukocyte chemotactic migration. Then, we used this model to screen the hit compound and evaluate its biological activity on leukocyte chemotactic migration. Furthermore, western blot analysis was performed to evaluate the effect of the hit compound on the AKT or ERK-mediated pathway, which plays an important role in leukocyte chemotactic migration. Results: In this study, using zebrafish-based chemical screening, we identified that the hit compound meisoindigo (25 μM, 50 μM, 75 μM) can significantly inhibit zebrafish leukocyte chemotactic migration in a dose-dependent manner (p = 0.01, p = 0.0006, p < 0.0001). Also, we found that meisoindigo did not affect the process of leukocyte reverse migration (p = 0.43). Furthermore, our results unexpectedly showed that indirubin, the core structure of meisoindigo, had no significant effect on zebrafish leukocyte chemotactic migration (p = 0.6001). Additionally, our results revealed that meisoindigo exerts no effect on the Akt or Erk-mediated signalling pathway. Discussion and conclusion: Our results suggest that meisoindigo, but not indirubin, is effective for inhibiting leukocyte chemotactic migration, thus providing a potential therapeutic agent for treating inflammatory diseases.
Different Effects of Antihypertensive Regimens Based on Fosinopril or Hydrochlorothiazide With or Without Lipid Lowering by Pravastatin on Progression of Asymptomatic Carotid Atherosclerosis: Principal Results of PHYLLIS—A Randomized Double-Blind Trial

Background and Purpose— The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies. Methods— A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBMmax). Results— CBMmax significantly progressed (0.010±0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBMmax changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. “Clinic” and “ambulatory” blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by ≈1 mmol/L in groups C and D. Conclusions— Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.
Maintaining Quality Care during a Nursing Shortage Using Licensed Practical Nurses in Acute Care

Implications of an aging registered nurse workforce, coupled with an inadequate supply of new nurses, presented a unique challenge for the nurse executive in an acute care hospital. This article presents one possible solution: reintroduction of licensed practical nurses to the patient care setting. It describes a pilot project initiated to answer the following question: Is there a change in quality of patient care or staff satisfaction when the nursing care delivery system adds a licensed practical nurse to the registered nurse and patient care assistant care pairs? It also describes the driving forces behind this practice change and presents focus group discussions, the implementation process, and conclusions and recommendations.
Sex Differences in Mechanisms of Hypertension Associated With Obesity

Obesity is on a fast track to become the most costly and burdensome health epidemic worldwide. Comorbidities associated with obesity include type II diabetes mellitus and cardiovascular disease (CVD), of which hypertension is a highly prevalent and significant risk factor. Rising hypertension rates in both men and women are closely correlated with, and largely attributable to, rising rates of obesity.1,2 Currently, ≤70% of essential hypertension cases are associated with obesity.1 Understanding the mechanisms that lead to obesity-associated hypertension is vital to treat this growing patient population. However, there is a significant deficit of reports examining sex differences in obesity-associated hypertension in the literature to date because research efforts have been overwhelmingly restricted to male animals, and many clinical reports fail to separate results by sex. The National Institutes of Health, American Heart Association, and others have begun to raise awareness of sex discrepancies in research, and as a result, there has been an increase in publications highlighting differences in mechanisms associated with obesity-associated hypertension in females versus males. This review will summarize current knowledge of (1) epidemiological data of sex discrepancies in obesity-associated hypertension, (2) the sex specificity of the effects of obesity on sympathoactivation and its role in hypertension, (3) the potential role of leptin in sex differences in obesity-associated hypertension, (4) the influence of female sex hormones on leptin and obesity-associated hypertension, and (5) sex differences in renin–angiotensin–aldosterone system activation in obesity. Population rates of obesity are not equal between men and women. Data from the NHANES study (National Health and Nutrition Examination Survey),3–5 REGARDS study (Reasons for Geographic and Racial Differences in Stroke),6 and Jackson Heart Study7 demonstrate that women have a higher obesity rate than men. Worldwide, the prevalence of obesity in women is higher than men …
[Clinical examination of acetated Ringer solution in patients with normal liver function and those with liver dysfunction].

Acetated Ringer solution (AR) was studied clinically to find its usefulness in patients with liver dysfunction compared with lactated Ringer solution (LR). The thirty-eight patients scheduled to be operated were divided into four groups (Group I: with normal liver function and AR infused, Group II: with normal liver function and LR infused, Group III: with liver dysfunction and AR infused, Group IV: with liver dysfunction and LR infused). AR or LR was administered to each group at a speed of 10 ml.kg-1.h-1, and we investigated the differences of these four groups clinically. L-lactic acid increased significantly in all groups after administration of AR or LR. D-lactic acid increased in LR groups, and acetic acid increased in AR groups. However, the other parameters, including the acid-base balance, electrolytes and liver function, showed no significant changes in any group. Therefore the status of liver dysfunction did not affect the metabolism of lactic acid in this study. These findings indicate that as an intraoperative fluid, AR is just as useful as LR. However, there was no significant difference between the data of AR groups compared with those of LR groups. In conclusion, AR is not necessarily a better fluid compared with LR as an intraoperative fluid in patients with liver dysfunction.
Assessing structure and function of myelin in cervical spondylotic myelopathy

Purpose: To assess the extent of demyelination in cervical spondylotic myelopathy (CSM) using myelin water imaging (MWI) and electrophysiologic techniques. Methods: Somatosensory evoked potentials (SSEPs) and MWI were acquired in 14 patients with CSM and 18 age-matched healthy controls. MWI was performed on a 3.0T whole body magnetic resonance scanner. Myelin water fraction (MWF) was extracted for the dorsal columns and whole cord. SSEPs and MWF were also compared with conventional MRI outcomes, including T2 signal intensity, compression ratio, maximum spinal cord compression (MSCC), and maximum canal compromise (MCC). Results: Group analysis showed marked differences in T2 signal intensity, compression ratio, MSCC, and MCC between healthy controls and patients with CSM. There were no group differences in MWF and SSEP latencies. However, patients with CSM with pathologic SSEPs exhibited reduction in MWF (p < 0.05). MWF was also correlated with SSEP latencies. Conclusion: Our findings provide evidence of decreased myelin content in the spinal cord associated with impaired spinal cord conduction in patients with CSM. While conventional MRI are of great value to define the extent of cord compression, they show a limited correlation with functional deficits (i.e., delayed SSEPs). MWI provides independent and complementary readouts to spinal cord compression, with a high specificity to detect impaired conduction.