Miracle-dz/UniFAR-FTUs huggingface dataset:
Topical ketorolac in vitreoretinal surgery: a prospective, randomized, placebo-controlled, double-masked trial.

OBJECTIVE To evaluate the effects of topical ketorolac in patients undergoing vitreoretinal surgery. METHODS One hundred nine patients undergoing vitrectomies were randomized to receive either topical ketorolac tromethamine, 0.4%, or placebo. Patients were instructed to begin taking the study medication 3 days preoperatively (4 times daily) and to continue taking it 4 weeks postoperatively. MAIN OUTCOME MEASURES Intraoperative pupil diameter, postoperative day 1 pain and inflammation, 1-month postoperative retinal thickness, and preoperative and 1-month postoperative best-corrected visual acuities. RESULTS The difference in mean pupil diameters between patients using ketorolac and those taking placebo was 0.06 mm (P = .39). Patients taking ketorolac and those taking placebo had mean pain scores (scale, 1-10) of 0.24 (SD, 0.6) and 1.06 (SD, 2) (P = .03) and mean inflammation grades (grade, 0-4) of 0.59 (SD, 0.7) and 1.16 (SD, 0.9) (P < .001), respectively. Ketorolac reduced central subfield thickness by 8%, but this was not statistically significant. At 1 month, mean visual acuities improved to 0.40 logMAR units (mean Snellen, 20/50; SD, 0.28 logMAR units) in the ketorolac group from 0.83 logMAR units (20/150(+2); SD, 0.60 logMAR units) at baseline and to 0.67 logMAR units (20/100(+1); SD, 0.46 logMAR units) in the placebo group from 0.92 logMAR units (20/150(-2); SD, 0.62 logMAR units) at baseline (P = .001). CONCLUSIONS Topical ketorolac was well tolerated and safe, reduced postoperative pain and inflammation, and improved visual recovery in this prospective, double-masked trial. APPLICATION TO CLINICAL PRACTICE Topical ketorolac may benefit patients undergoing vitreoretinal surgery. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00576329.
Renal hemodynamic effects of exogenously administered adenosine and polyadenylic acid.

Steady-state intrarenal arterial infusion of adenosine (Ado) suggests that there may be both afferent and efferent arteriolar actions of Ado. This study attempts to further differentiate vascular sites of action of Ado during an intrarenal infusion of Ado. We measured the filtration fraction (FF) during intrarenal infusion of Ado (33.3 nmol.kg-1 x min-1) in anesthetized dogs to determine its transient actions on renal hemodynamics. FF remained unchanged from preinfusion levels (0.42 +/- 0.01 vs. 0.46 +/- 0.01, respectively) at a time when renal blood flow (RBF) was significantly decreased (52 +/- 6% of control). During steady state, RBF was 96 +/- 5% of control, while FF was significantly decreased from control (0.27 +/- 0.02). To determine whether vasoconstriction and dilation to Ado are mediated by receptors accessible from intra- or extravascular compartments, two Ado analogues [oligoadenylic acid (oligo[A]), mol wt 5,000, and polyadenylic acid (poly[A]), mol wt > 100,000] were injected into the renal artery, and RBF response was compared with that of Ado. Poly[A] produced a transient vasodilation (42 +/- 6% increase in RBF), whereas oligo[A] produced a transient vasoconstriction (25 +/- 5% decrease in RBF). Responses to steady-state infusion of poly[A] (10 nmol.kg-1 x min-1) were determined in 11 anesthetized sodium-depleted dogs. Poly[A] produced a sustained significant increase in RBF from 2.83 +/- 0.31 to 3.92 +/- 0.40 ml.g-1 x min-1. This decrease in renal vascular resistance was blocked by an intrarenal infusion of the Ado antagonist theophylline (0.5 mumol.kg-1 x min-1, 2.68 +/- 0.38 vs. 2.85 +/- 0.38 ml.g-1 x min-1). (ABSTRACT TRUNCATED AT 250 WORDS)
Anxiety Disorders: Similarities and Differences of Comorbidity in Treated and Untreated Groups

The similarities and differences of comorbidity in treated and untreated samples with anxiety disorders were examined using data from the Munich Follow-up Study: 133 subjects with anxiety and depressive disorders and 101 former in-patients at the Max Planck Institute for Psychiatry. Diagnoses were based on the DIS, not using the optional DSM—III exclusion rules. In these epidemiological and clinical samples, 69% and 95% respectively had at least two diagnoses. The epidemiological sample was clearly differentiated from the clinical sample by age of onset. The development of both depressive episodes and substance disorders in the two samples was mostly secondary to the development of anxiety problems. The outcome for subjects with both anxiety and depressive disorders tended to be worse than that for those with anxiety alone, regardless of whether a depressive episode was present at the time of the follow-up investigation. The usefulness is underlined of the comorbidity concept based on operationalised diagnosis without the exclusion rules offered by DSM—III and DSM—III—R.
Pharmacodynamics and Pharmacokinetics of High‐Dose Sufentanil in Infants and Children Undergoing Cardiac Surgery

The pharmacodynamic and pharmacokinetic profiles of high-dose sufentanil (15 μg/kg) and oxygen were determined in 20 infants and children undergoing repair of congenital heart defects. Sufentanil provided marked hemodynamic stability after an infusion and during the stress periods of incision and sternotomy. Two patients required supplemental nitrous oxide because of an increase in blood pressure greater than 20% of baseline. Mean plasma catecholamine concentrations varied widely among patients and increased, although not significantly, during intraoperative stress. Pharmacokinetic data best fit a two-compartment model. In infants younger than 10 months (group 1) and children older than 10 months (group 2) who were not surface-cooled, elimination half-lives were similar (mean ± sd 53 ± 15 min vs 55 ± 10 min) as were clearance values (27.5 ± 9.3 vs 18.1 ± 10.7 ml·kg−1·min−1). However, the volumes of distribution were significantly smaller in group 1 compared with group 2 (1.6 ± 0.46 us 3.0 ± 1.3 L/kg). In infants younger than 10 months who were surface-cooled (group 3) elimination half-life was longer (120 ± 36 min) and volume of distribution larger (3.7 ± 1.1 L/kg), but clearance rate was similar (21.5 ± 5.0 ml·kg −1·min−1 compared with age- and weight-matched infants (group 1).
Dual Add-on Therapy in Type 2 Diabetes Poorly Controlled With Metformin Monotherapy: A Randomized Double-Blind Trial of Saxagliptin Plus Dapagliflozin Addition Versus Single Addition of Saxagliptin or Dapagliflozin to Metformin

OBJECTIVE This study compared the efficacy and safety of dual add-on of saxagliptin plus dapagliflozin versus saxagliptin and dapagliflozin added on alone in patients with type 2 diabetes poorly controlled with metformin. RESEARCH DESIGN AND METHODS This was a double-blind trial in adults with HbA1c ≥8.0% and ≤12.0% (64–108 mmol/mol), randomized to saxagliptin (SAXA) (5 mg/day) plus dapagliflozin (DAPA) (10 mg/day; n = 179), or SAXA (5 mg/day) and placebo (n = 176), or DAPA (10 mg/day) and placebo (n = 179) on background metformin extended release (MET) ≥1,500 mg/day. Primary objective compared changes from baseline in HbA1c with SAXA+DAPA+MET versus SAXA+MET and DAPA+MET. RESULTS Patients had a mean baseline HbA1c of 8.9% (74 mmol/mol), diabetes duration of 7.6 years, and a BMI of 32 kg/m2. At week 24, the adjusted mean change from the baseline HbA1c was –1.5% (–16.1 mmol/mol) with SAXA+DAPA+MET versus –0.9% (–9.6 mmol/mol) with SAXA+MET (difference −0.59% [–6.4 mmol/mol], P < 0.0001) and –1.2% (–13.1 mmol/mol) with DAPA+MET (difference −0.27% [3.0 mmol/mol], P < 0.02). The proportion of patients achieving HbA1c <7% (53 mmol/mol) was 41% with SAXA+DAPA+MET versus 18% with SAXA+MET and 22% with DAPA+MET. Urinary and genital infections occurred in ≤1% of patients receiving SAXA+DAPA+MET. Hypoglycemia was infrequent, with no episodes of major hypoglycemia. CONCLUSIONS In this first report of adding a well-tolerated combination of saxagliptin plus dapagliflozin to background metformin therapy in patients poorly controlled with metformin, greater improvements in glycemic control were obtained with triple therapy by the dual addition of saxagliptin and dapagliflozin than dual therapy with the addition of saxagliptin or dapagliflozin alone.
Daily Smoking and Subjective Health Complaints in Adolescence

Introduction: Using data from the Health Behaviour in School-aged Children survey, this study used a repeated cross-sectional design to examine associations between daily smoking, gender, and self-reported health complaints in five cohorts of adolescents over a 16-year period. Methods: Data were from nationally representative cohorts of 15-year-old youth in Norway in 1993/1994, 1997/1998, 2001/2002, 2005/2006, and 2009/2010 (n total = 7761). Dependent variables were psychological, somatic, and total health complaints. A mixed GLM model examined main and interaction effects of smoking (daily, intermittent, nonsmoking), year, and gender in predicting complaints. Time periods were segmented to compare trends across smoking groups in specific periods. Results: Prevalence of daily smoking declined from 15.5% (1993/1994) to 6.0% (2009/2010). All health complaint scores were significantly higher for smokers and for girls (vs. boys). Smoking status by year interactions were significant for all complaint variables during the period of sharpest decline of daily smoking prevalence (2001/2002–2005/2006), with daily smokers experiencing increases in health complaints while intermittent and nonsmokers did not. Smoking status by gender interactions were significant for all health complaint variables, indicating that the main effect for gender (females higher) was even stronger among smokers compared with nonsmokers. Using year as unit of analysis, the size of mean differences between daily smokers and intermittent/nonsmokers in total complaints was significantly negatively correlated with daily smoking prevalence (−.963, n = 5, p < .01). Conclusions: As prevalence of daily smoking declined, daily smokers reported higher levels of complaints, suggesting increasing health problems within this group. Girls who smoke daily had particularly elevated levels of complaints. Implications: This study indicates that the relationship between daily smoking and concurrent health symptomatology in adolescents is changing over time, with higher levels of health complaints reported as overall smoking prevalence declines. To our knowledge, this finding has not previously been reported. If youth are smoking to cope with distress, pain, or other health concerns, tobacco control objectives will be increasingly difficult to achieve with adolescents. Levels of health complaints are particularly high among girls who are daily smokers. The findings suggest that restrictive measures and persuasive communications may not be sufficient tobacco prevention strategies for adolescent populations. Young smokers may need counseling and support.
Physical inactivity and platelet function in humans and brown bears: A comparative study

Abstract Physical inactivity increases the risk of thromboembolism. However, good standardized human models on inactivity are in short supply and experimental models are few. Our objective was to investigate how standardized bed rest affects platelet aggregation in humans and to investigate if aggregation is altered in a translational model system – the hibernating brown bear (Ursus arctos). We collected blood from (1) healthy male volunteers participating in a 21-day bed rest study in head-down tilt position (−6°) 24 h a day; (2) free-ranging brown bears captured during winter hibernation and again during active state in summer. We analyzed platelet function using multiple electrode platelet aggregometry. In total, 9 healthy male volunteers (age 31.0 ± 6.4 years) and 13 brown bears (7 females and 6 males, age 2.8 ± 0.6 years) were included. In hibernating bears adenosine diphosphate, arachidonic acid, thrombin receptor activating peptide, and collagen impedance aggregometry tests were all halved compared to summer active state. In human volunteers no statistically significant changes were found between baseline and the end of bed rest. In human male volunteers 3 weeks of bed rest did not affect platelet function. In hibernating brown bears platelet aggregation was halved compared to summer and we hypothesize that this is a protective measure to avoid formation of thrombi under periods of low blood flow.
Temporal synthesis and release of endothelin within the systemic and myocardial circulation during and after cardiopulmonary bypass: relation to postoperative recovery.

OBJECTIVE To determine endothelin levels in arterial, pulmonary, and myocardial vascular compartments in patients undergoing coronary artery bypass graft surgery and to examine the influence of endothelin on postoperative recovery. DESIGN Prospective, clinical study. SETTING University hospital. PARTICIPANTS Fifty patients undergoing elective coronary artery bypass graft surgery. INTERVENTIONS Endothelin plasma content (fmol/mL) was measured in 50 patients undergoing coronary revascularization from various vascular compartments before surgery and at specific intervals up to 24 hours postoperatively. MEASUREMENTS AND MAIN RESULTS Myocardial endothelin gradient (coronary sinus - aorta) was calculated before cardiopulmonary bypass (CPB), at release of the aortic cross-clamp, immediately after CPB, and 0.5 hour after CPB. The requirement for inotropic therapy and duration of patient stay in the intensive care unit were determined. Systemic and pulmonary endothelin levels were increased by >80% immediately after CPB when compared with preoperative values and increased again by approximately 60% during the first 24 hours postoperatively (p < 0.05). The myocardial endothelin gradient was reversed after CPB, indicating myocardial production of endothelin (pre-CPB, -0.72+/-0.39 fmol/mL v 0.5 hour post-CPB, 0.60+/-0.49 fmol/mL; p < 0.05). Longer intensive care unit times (>28 hours) were associated with higher systemic endothelin levels when compared with shorter times (<18 hours) (16.30+/-1.33 fmol/mL v 9.81+/-1.67 fmol/mL; p < 0.05). Patients with higher endothelin levels 6 hours postoperatively had greater inotropic requirements during the intensive care unit period. CONCLUSION Endothelin levels after CPB remained persistently increased for at least 24 hours after surgery and were associated with increased myocardial production of endothelin. These results suggest that the increased endothelin observed in the early postoperative period may contribute to a complex recovery from coronary artery bypass graft surgery.
Effect of heavy metals combined stress on growth and metals accumulation of three Salix species with different cutting position

ABSTRACT This study aimed to compare growth performance and heavy metal (HM) accumulation at different cutting positions of Salix species grown in multi-metal culture. Three Salix species stems cut at different positions (apical to basal) were grown hydroponically for four weeks. The plants were then treated for three weeks with 0, 5, 10, and 20 μM Cd, Cu, Pb, and Zn, resulting in total metal concentrations of 0, 20, 40, and 80 μM. The growth parameters and HM content in shoots and initial cutting were measured. Results showed that, compared with S. fragilis, S. matsudana grew more poorly in uncontaminated condition but grew better and accumulated lower metal in shoots under mixed HM treatment. In addition, cuttings from apical parent stem position exhibited poorer growth performance before and after treatment, as well as greater metal content in shoots than base parts under the HM treatment. These results suggest that S. matsudana may undergo a special mechanism to hinder metals in the initial cutting, thus mitigating growth damage. The apical portion also showed poor resistance against the invasion of mixed HMs because of the immature structure. Therefore, in the selection of phytoremediation plants, metal accumulation ability is not proportional to growth performance.
Distinct Biochemical and Functional Properties of Two Rab5 Homologs from the Rice Blast Fungus Magnaporthe oryzae*

Background: It is unclear if the two Rab5 homologs in M. oryzae (MoRab5A and MoRab5B) are functional Rab5 orthologs. Results: Only MoRab5B resembles mammalian Rab5, while MoRab5A exhibits reduced GTPase and endocytosis activities. Conclusion: MoRab5B is the Rab5 ortholog. Significance: The study highlights that Rab5 homologs in fungi are not simply redundant Rab5 isoforms but represent distinct endosomal Rab functions. Rab5 is a key regulator of early endocytosis by promoting early endosomal fusion and motility. In this study, we have unexpectedly found distinct properties of the two Rab5 homologs (MoRab5A and MoRab5B) from Magnaporthe oryzae, a pathogenic fungus in plants whose infection causes rice blast disease. Like mammalian Rab5, MoRab5A and MoRab5B can bind to several Rab5 effectors in a GTP-dependent manner, including EEA1, Rabenosyn-5, and Rabaptin-5. However, MoRab5A shows distinct binding characteristics in the sense that both the wild-type and the GTP hydrolysis-defective constitutively active mutant bind the effectors equally well in GST pull-down assays, suggesting that MoRab5A is defective in GTP hydrolysis and mostly in the GTP-bound conformation in the cell. Indeed, GTP hydrolysis assays indicate that MoRab5A GTPase activity is dramatically lower than MoRab5B and human Rab5 and is insensitive to RabGAP5 stimulation. We have further identified a Pro residue in the switch I region largely responsible for the distinct MoRab5A properties by characterization of MoRab5A and MoRab5B chimeras and mutagenesis. The differences between MoRab5A and MoRab5B extend to their functions in the cell. Although they both target to early endosomes, only MoRab5B closely resembles human Rab5 in promoting early endosome fusion and stimulating fluid phase endocytosis. In contrast, MoRab5A correlates with another related early endosomal Rab, Rab22, in terms of the presence of the switch I Pro residue and the blocked GTPase activity. Our data thus identify MoRab5B as the Rab5 ortholog and suggest that MoRab5A specializes to perform a non-redundant function in endosomal sorting.
Dietary Supplementation with Vitamin E Reverses the Age-related Deficit in Long Term Potentiation in Dentate Gyrus*

Long term potentiation (LTP) in dentate gyrus is impaired in aged rats, and this has been associated with an age-related decrease in membrane arachidonic acid concentration. In this study, we considered whether the trigger for this age-related decrease in arachidonic acid might be increased lipid peroxidation stimulated by the proinflammatory cytokine, interleukin-1β. Groups of aged and young rats were fed on a control diet or a diet supplemented with α-tocopherol and assessed for their ability to sustain LTP. Aged rats fed on the control diet exhibited an impaired ability to sustain LTP and analysis of tissue prepared from these rats exhibited increased interleukin-1β, increased lipid peroxidation, and decreased membrane arachidonic acid concentration compared with young rats fed on either diet. Aged rats fed on the supplemented diet sustained LTP in a manner indistinguishable from young rats, and the age-related increases in interleukin-1β and lipid peroxidation and the decrease in membrane arachidonic acid concentration were all reversed. We propose that interleukin-1β may be the trigger that induces these age-related changes and may therefore be responsible for the deficit in long term potentiation in aged rats. The observation that α-tocopherol reverses these changes is consistent with the hypothesis that some age-related changes in hippocampus might derive from oxidative stress.
Nose to brain microemulsion-based drug delivery system of rivastigmine: formulation and ex-vivo characterization

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to irreversible loss of neurons, cognition and formation of abnormal protein aggregates. Rivastigmine, a reversible cholinesterase inhibitor used for the treatment of AD, undergoes extensive first-pass metabolism, thus limiting its absolute bioavailability to only 36% after 3-mg dose. Due to extreme aqueous solubility, rivastigmine shows poor penetration and lesser concentration in the brain thus requiring frequent oral dosing. This investigation was aimed to formulate microemulsion (ME) and mucoadhesive microemulsions (MMEs) of rivastigmine for nose to brain delivery and to compare percentage drug diffused for both systems using in-vitro and ex-vivo study. Rivastigmine-loaded ME and MMEs were prepared by titration method and characterized for drug content, globule size distribution, zeta potential, pH, viscosity and nasal ciliotoxicity study. Rivastigmine-loaded ME system containing 8% w/w Capmul MCM EP, 44% w/w Labrasol:Transcutol-P (1:1) and 48% w/w distilled water was formulated, whereas 0.3% w/w chitosan (CH) and cetyl trimethyl ammonium bromide (as mucoadhesive agents) were used to formulate MMEs, respectively. ME and MMEs formulations were transparent with drug content, globule size and zeta potential in the range of 98.59% to 99.43%, 53.8 nm to 55.4 nm and −2.73 mV to 6.52 mV, respectively. MME containing 0.3% w/w CH followed Higuchi model (r2 = 0.9773) and showed highest diffusion coefficient. It was free from nasal ciliotoxicity and stable for three months. However, the potential of developed CH-based MME for nose to brain delivery of rivastigmine can only be established after in-vivo and biodistribution study.
Integrating means-end chains and the Kano model to understand tourists’ cognitive structure toward leisure and recreational resources of suburban-mountains

ABSTRACT This study integrates the means-end chain (MEC) theory and Kano model to better understand tourists’ inner thinking toward the leisure and recreation resources of suburban-mountains, and help in prioritizing decisions on mountain recreational resource management for the government and related managerial officers. A total of 303 valid responses from individuals aged over 50 years with the habit of hiking in this area at least once a week were collected for MEC and Kano analyses. The results of the hybrid hierarchical value map show that one-dimensional attributes (i.e. “water resources, “providing cultural and educational facilities,” “providing hiking trails,” “providing scenic overlook and pavilion,” “providing guardrails,” and “providing resting area”) are the priorities that the government and managers should pay the most attention to for the elderly people hiking the suburban-mountains. By following the same deduction process proposed in this study, the rest of the one-dimensional consequences and values can be depicted. Finally, the theoretical and managerial implications as well as the limitations of this work are also provided. This study can not only enrich the theoretical development of MEC theory, but also provide the government with valuable information to enhance the leisure and recreation resources of suburban-mountain areas for elderly tourists.