nils-herrmann/clean_scirepeval huggingface dataset:
Thyroid Hormone Activates Brown Adipose Tissue and Increases Non-Shivering Thermogenesis - A Cohort Study in a Group of Thyroid Carcinoma Patients

Thyroid hormone receptors are present on brown adipose tissue (BAT), indicating a role for thyroid hormone in the regulation of BAT activation. The objective of this study was to examine the effect of thyroid hormone withdrawal followed by thyroid hormone in TSH-suppressive dosages, on energy expenditure and brown adipose tissue activity.



This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to treatment protocol). Paired two-tailed t-tests and linear regression analyses were used.



Basal metabolic rate (BMR) was significantly higher after treatment with synthetic thyroid hormone (levothyroxine) than in the hypothyroid state (BMR 3.8 ± 0.5 kJ/min versus 4.4 ± 0.6 kJ/min, P = 0.012), and non-shivering thermogenesis (NST) significantly increased from 15 ± 10% to 25 ± 6% (P = 0.009). Mean BAT activity was significantly higher in the subclinical hyperthyroid state than in the hypothyroid state (BAT standard uptake value (SUVMean) 4.0 ± 2.9 versus 2.4 ± 1.8, P = 0.039).



Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT.
Efficacy and safety of milnacipran 100 mg/day in patients with fibromyalgia: results of a randomized, double-blind, placebo-controlled trial.

To assess the efficacy and safety of milnacipran at a dosage of 100 mg/day (50 mg twice daily) for monotherapy treatment of fibromyalgia.



A double-blind, placebo-controlled trial was performed to assess 1,025 patients with fibromyalgia who were randomized to receive milnacipran 100 mg/day (n = 516) or placebo (n = 509). Patients underwent 4-6 weeks of flexible dose escalation followed by 12 weeks of stable-dose treatment. Two composite responder definitions were used as primary end points to classify the response to treatment. The 2-measure composite response required achievement of ≥30% improvement from baseline in the pain score and a rating of "very much improved" or "much improved" on the Patient's Global Impression of Change (PGIC) scale. The 3-measure composite response required satisfaction of these same 2 improvement criteria for pain and global status as well as improvement in physical function on the Short Form 36 (SF-36) physical component summary (PCS) score.



After 12 weeks of stable-dose treatment, a significantly greater proportion of milnacipran-treated patients compared with placebo-treated patients showed clinically meaningful improvements, as evidenced by the proportion of patients meeting the 2-measure composite responder criteria (P < 0.001 in the baseline observation carried forward [BOCF] analysis) and 3-measure composite responder criteria (P < 0.001 in the BOCF). Milnacipran-treated patients also demonstrated significantly greater improvements from baseline on multiple secondary outcomes, including 24-hour and weekly recall pain score, PGIC score, SF-36 PCS and mental component summary scores, average pain severity score on the Brief Pain Inventory, Fibromyalgia Impact Questionnaire total score (all P < 0.001 versus placebo), and Multidimensional Fatigue Inventory total score (P = 0.036 versus placebo). Milnacipran was well tolerated by most patients, with nausea being the most commonly reported adverse event (placebo-adjusted rate of 15.8%).



Milnacipran administered at a dosage of 100 mg/day improved pain, global status, fatigue, and physical and mental function in patients with fibromyalgia.
Pharmacodynamics of diazepam co-administered with methadone or buprenorphine under high dose conditions in opioid dependent patients.

Benzodiazepine abuse is common among methadone- and buprenorphine-maintained patients; however interactions between these drugs under high dose conditions have not been adequately examined under controlled conditions.



To investigate the effects of co-administering diazepam with methadone or buprenorphine under high dose conditions.



Double-blind, randomly ordered, 2 x 2 cross-over design in which the effects of diazepam dose (0mg versus 40 mg) and opioid dose (100% versus 150% normal dose) were examined over four sessions in methadone- and buprenorphine-maintained patients.



Four methadone- and seven buprenorphine-prescribed patients without concurrent dependence on other substances or significant medical co-morbidity.



Physiological (pulse rate, blood pressure, pupil size, respiratory rate and peripheral SpO2), subjective (ARCI, VAS ratings) and performance (reaction time, cancellation task and Digit Symbol Substitution Test, DSST) measures were taken prior to and for 6h post-dosing.



High dose diazepam was associated with time-dependent increases in the intensity of subjective drug effects (strength of drug effect, sedation) and decreases in psychological performance (reaction time, DSST) for both methadone and buprenorphine patients. These effects were generally independent of the opioid dose administered. High dose opioid administration (150% normal dose) was associated with reductions in overall SpO2 levels and performance (reaction time, DSST) in the methadone patients, but had virtually no impact on pharmacodynamic responses in the buprenorphine group.



High dose diazepam significantly alters subjective drug responses and psychological performance in patients maintained on methadone and buprenorphine.
Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice

Insulin-degrading enzyme (IDE) is a protease that cleaves insulin and other bioactive peptides such as amyloid-β. Knockout and genetic studies have linked IDE to Alzheimer's disease and type-2 diabetes. As the major insulin-degrading protease, IDE is a candidate drug target in diabetes. Here we have used kinetic target-guided synthesis to design the first catalytic site inhibitor of IDE suitable for in vivo studies (BDM44768). Crystallographic and small angle X-ray scattering analyses show that it locks IDE in a closed conformation. Among a panel of metalloproteases, BDM44768 selectively inhibits IDE. Acute treatment of mice with BDM44768 increases insulin signalling and surprisingly impairs glucose tolerance in an IDE-dependent manner. These results confirm that IDE is involved in pathways that modulate short-term glucose homeostasis, but casts doubt on the general usefulness of the inhibition of IDE catalytic activity to treat diabetes.
Total disc replacement in the treatment of lumbar discogenic pain with disc herniation: a prospective clinical study.

Biomechanical benefits of Total Disc Replacement (TDR) including both the restoration of normal segmental range of motion and the prevention of physiological lumbar lordosis encourage spine surgeons to perform TDR for lumbar disc disease.



A total of twenty patients (mean age: 39.5) who had degenerative disc disease with unilateral disc herniation were operated on between 2003 and 2006. Microscopic anterior lumbar discectomy with TDR placement via a transperitoneal approach were performed. Each patient was evaluated using a VAS and the Oswestry index.



Mean ODI improved from 73.3 preoperatively to 35.0 and 20.4 at 3 and 12 months of follow-up respectively (P < 0.001). The mean VAS score improved from 8.65 preoperatively to 2.6 and 1.9 at 3 and 12 months respectively (P < 0.001).



Results from this series are promising and indicate that placement of TDR for degenerative disc disease with lumbar disc herniation is a valuable alternative to conventional techniques. The main advantages of this application are preservation of spinal stability, early mobilization, restoration of normal segmental range of motion and elimination of problems related to intervertebral disc tissue such as discogenic pain and recurrence of disc herniation.
Medroxyprogesterone in postmenopausal females with partial upper airway obstruction during sleep.

The aim of the present study was to evaluate the degree and duration of respiratory stimulation caused by medroxyprogesterone acetate (MPA), and compare the effect of MPA to that of nasal continuous positive airway pressure (nCPAP) in sleep-disordered breathing. Ten postmenopausal females with predominantly partial upper airway obstruction during sleep had an overnight sleep study at baseline, on the fourteenth day of treatment with MPA and after a 3-week washout period. Six subjects on nCPAP were also studied 3 months later. At baseline, the overnight mean+/-SD end-tidal pressure of carbon dioxide (Pet,CO2) was 5.5+/-0.4 kPa the arterial oxygen saturation (Sa,O2) 93.0+/-1.2%, Sa,O2 nadir 80.0+/-6.7%, and frequency of oxygen desaturation > or = 4% (ODI4) per hour 2.2+/-1.3. MPA decreased Pet,CO2 by 0.8 kPa (14.5%, p<0.001). After washout, the mean Pet,CO2 remained at 0.5 kPa (9.1%, p<0.001) lower than at baseline. Sa,O2 did not change. Pet,CO2 was lower on MPA than on nCPAP (4.7+/-0.2 kPa versus 5.0+/-0.3 kPa; p=0.037) but Sa,O2 was similar. Apnoea/hypopnoea index tended to be lower on CPAP than on MPA. Medroxyprogesterone acetate at a daily dose of 60 mg improves ventilation in postmenopausal females with partial upper airway obstruction during sleep without compromising sleep. The ventilatory improvement is sustained for at least 3 weeks posttreatment. Medroxyprogesterone acetate was more efficient in decreasing the partial pressure of carbon dioxide but continuous positive airway pressure was superior in decreasing respiratory efforts.
Multifamily psychoeducation for improvement of mental health among relatives of patients with major depressive disorder lasting more than one year: study protocol for a randomized controlled trial

Major depressive disorder (MDD) is a long-lasting disorder with frequent relapses that have significant effects on the patient's family. Family psychoeducation is recognized as part of the optimal treatment for patients with psychotic disorder. A previous randomized controlled trial has found that family psychoeducation is effective in enhancing the treatment of MDD. Although MDD can easily become a chronic illness, there has been no intervention study on the families of patients with chronic depression. In the present study, we design a randomized controlled trial to examine the effectiveness of family psychoeducation in improving the mental health of relatives of patients with MDD lasting more than one year.



Participants are patients with MDD lasting more than one year and their relatives. Individually randomized, parallel-group trial design will be employed. Participants will be allocated to one of two treatment conditions: relatives will receive (a) family psychoeducation (four, two-hour biweekly multifamily psychoeducation sessions) plus treatment-as-usual for the patient (consultation by physicians), or (b) counseling for the family (one counseling session from a nurse) plus treatment-as-usual for the patient. The primary outcome measure will be relatives' mental health as measured by K6 that was developed to screen for DSM-IV depressive and anxiety disorder. Additionally, the severity of depressive symptoms in patients measured by the Beck Depression Inventory-II (BDI-II) scale will be assessed. Data from the intention-to-treat sample will be analyzed 16 weeks after randomization.



This is the first study to evaluate the effectiveness of family psychoeducation for relatives of patients with MDD lasting more than one year. If this type of intervention is effective, it could be a new method of rehabilitation for patients with MDD lasting more than one year.
Clinical evaluation of De Marco formula as an adjunctive therapy for infected ischemic diabetic foot: a prospective randomized controlled trial.

De Marco Formula (DMF) is a novel formulation of procaine and PVP.



To assess the efficacy and safety of DMF as an adjunctive therapy for infected ischemic diabetic foot in a prospective randomized controlled clinical trial.



Adult patients, 39 male/ 79 female, were randomly assigned (59 patients/treatment group) to the conventional therapy alone (A) or plus DMF (0, 15 ml/kg .day i.m.) during ten days and them twice a week until healing of the lesions or completion of 52 days (B).The response to the treatment was considered favorable when an amputation was not needed even though a decrease of the wound area or complete healing was not shown. It was considered unfavorable when a major amputation was necessary because of worsening of the lesion (wound spreading to any magnitude greater than the initial one) or the appearance of new wounds in the same leg.



Both groups were comparable with regard to age, sex, level of arterial occlusion, type of lesion, anatomic localization of lesions and previous surgical procedures. The cumulative percentage of unfavorable results was significantly lower after treatment B with respect to treatment A (25.4% vs. 45.8%; p= 0.02), for a reduction of 44.5%. Four slight adverse reactions were associated with DMF: vertigo and nausea at the 7th treatment administration (one patient), and headache and tachycardia at the 12th dose (another patient). Blood hemoglobin and leukocyte counts and serum alanine transaminase were not affected.



The treatment with DMF for 52 days as an adjuvant for the conventional therapy was associated with a lower need for major amputations. It was also well tolerated and safe.
Treatment of ischemic pain in patients suffering from peripheral vasculopathy with transdermal buprenorphine plus epidural morphine with ropivacaine vs. epidural morphine with ropivacaine.

This study compared the efficacy and safety of buprenorphine transdermal delivery system with peridural infusion of morphine and ropivacaine to peridural infusion alone for the control of ischemic pain in patients suffering from peripheral vasculopathy.



Eighty-six patients were randomized into two groups. In the first group, a buprenorphine patch 35 microg/hour TTDS (transtec transdermal device plus ropivacaine and morphine) was applied, and a peridural infusion of ropivacaine/morphine (200 mg + 2 mg) was established. In the second group, ropivacaine and morphine analgesia was obtained using a peridural infusion and a placebo patch. The primary efficacy parameter was the visual analog scale score for pain. Secondary parameters of efficacy were the short-form McGill Pain Questionnaire scores and a score for pain interference with sleep obtained from patient diaries evaluated every week for a period of 4 weeks.



Subjects in the TTDS group reported a reduction in pain, increased sleep, and a lower incidence of side effects compared with the control group.



Transdermal buprenorphine use resulted in significant pain relief with excellent patient satisfaction, which may translate into improvement in mood and quality of life.
Clinical and pharmacokinetic overview of parenteral etoposide phosphate

Etoposide phosphate (Etopophos, BMY-40481) is a water-soluble derivative of the widely used podophyllotoxin etoposide (VP-16). The phosphate ester renders the compound water-soluble, eliminating the need for formulation in polysorbate (Tween) 80, ethanol, and polyethylene glycol. As a result the compound can be given at high concentrations and as a bolus. In animals and in vitro, etoposide phosphate (EP) is rapidly and completely converted to VP-16. Clinical development of the i.v. formulation has focused on the identification of the maximum tolerated dose (MTD) and pharmacokinetic characteristics of the drug using a 5 daily dose schedule and a days 1, 3, and 5 schedule, with the drug being given over 30 or 5 (bolus) min. Myelosupression was dose-limiting. Data from these trials show the rapid and complete conversion of EP to VP-16, a pharmacokinetic/pharmacodynamic relationship for myelosuppression and exposure to VP-16, and an MTD of 100 and 150 mg/m2 (molar equivalent to VP-16) when EP is given daily for 5 days and on days 1, 3, and 5, respectively. A formal randomized trial has been conducted to show the pharmacokinetic comparability of EP and VP-16. In this trial, exposure to VP-16 was the same after the parenteral administration of equimolar doses of EP or VP-16. The feasibility of bolus dosing and treatment at high concentrations has been demonstrated, with no effects on the cardiovascular system being noted. Parenteral EP is pharmacokinetically and biologically equivalent to VP-16 and has the advantages of the elimination of potentially toxic excipients; more convenient administration; and ability to be given as a bolus, at high concentrations, and as a continuous infusion.
Does regular standing improve bowel function in people with spinal cord injury? A randomised crossover trial

A randomised crossover trial.To determine the effects of a 6-week standing programme on bowel function in people with spinal cord injury.Community, Australia and the United Kingdom.Twenty community-dwelling people with motor complete spinal cord injury above T8 participated in a 16-week trial. The trial consisted of a 6-week stand phase and a 6-week no-stand phase separated by a 4-week washout period. Participants were randomised to one of two treatment sequences. Participants allocated to the Treatment First group stood on a tilt table for 30 min per session, five times per week for 6 weeks and then did not stand for the next 10 weeks. Participants allocated to the Control First group did the opposite: they did not stand for 10 weeks and then stood for 6 weeks. Participants in both groups received routine bowel care throughout the 16-week trial. Assessments occurred at weeks 0, 7, 10 and 17 corresponding with pre and post stand and no-stand phases. The primary outcome was Time to First Stool. There were seven secondary outcomes reflecting other aspects of bowel function and spasticity.There were three dropouts leaving complete data sets on 17 participants. The mean (95% confidence interval) between-intervention difference for Time to First Stool was 0 min (−7 to 7) indicating no effect of regular standing on Time to First Stool.Regular standing does not reduce Time to First Stool. Further trials are required to test the veracity of some commonly held assumptions about the benefits of regular standing for bowel function.
Effect of Eye Movement Desensitization and Reprocessing (EMDR) on Depression in Patients With Myocardial Infarction (MI)

Coronary heart disease is the most important cause of death and inability in all communities. Depressive symptoms are frequent among post-myocardial infarction (MI) patients and may cause negative effects on cardiac prognosis. This study was conducted to identify efficacy of EMDR on depression of patients with MI.



This study is a clinical trial. Sixty patients with MI were selected by simple sampling, and were separated randomly into experimental and control groups. To collect data, demographic questionnaire and Beck Depression Questionnaire were used. In experimental group, EMDR therapy were performed in three sessions alternate days for 45-90 minutes, during four months after their MI. Depression level of patients was measured before, and a week after EMDR therapy. Data were analyzed using paired -t- test, t-test, and Chi-square.



The mean depression level in experimental group 27.26±6.41 before intervention, and it was 11.76±3.71 after intervention. Hence, it showed a statistically significant difference (P<0.001). The mean depression level in control group was 24.53±5.81 before intervention, and it was 31.66±6.09 after intervention, so it showed statistically significant difference (P<0.001). The comparison of mean depression level at post treatment, in both groups showed statistically significant difference (P<0.001).



EMDR is an effective, useful, efficient, and non-invasive method for treatment and reducing depression in patients with MI.
Depression and Oral FTC/TDF Pre-exposure Prophylaxis (PrEP) Among Men and Transgender Women Who Have Sex With Men (MSM/TGW)

We conducted a longitudinal and cross-sectional analysis of depressive symptomology in iPrEx, a randomized, placebo-controlled trial of daily, oral FTC/TDF HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. Depression-related adverse events (AEs) were the most frequently reported severe or life-threatening AEs and were not associated with being randomized to the FTC/TDF arm (152 vs. 144 respectively OR 0.66 95 % CI 0.35–1.25). Center for Epidemiologic Studies Depression scale (CES-D) and a four questions suicidal ideation scale scores did not differ by arm. Participants reporting forced sex at anal sexual debut had higher CES-D scores (coeff: 3.23; 95 % CI 1.24–5.23) and were more likely to have suicidal ideation (OR 2.2; 95 % CI 1.09–4.26). CES-D scores were higher among people reporting non-condom receptive anal intercourse (ncRAI) (OR 1.46; 95 % CI 1.09–1.94). We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services. Llevamos a cabo un análisis logitudinal y transversal de la sintomatologia depresiva en iPrEx, del estudio de placebo controlado, con seleccion de brazo al azar. Involucra tratamiento oral diario de FTC/TDF que esta usado como quimoprofilaxis de pre-exposicion (PrEP) contra VIH en hombres y mujeres transgénero que tienen relaciones sexuales con hombres (MSM/TGW). Eventos relacionados a depresion (AEs) fueron reportados como los sintomas mas adversos o de riesgo de vida. Estos no fueron asociados con la seleccion al azar del brazo FTC/TDF (152 contra 144 respectivamente; OR: 0.66; 95 % CI: 0.35-1.25). La escala de depresion (CES-D), que proviene del centro de Estudios Epidemiológicos de Depresion y un “filtro” con cuatro preguntas para detectar suicidios contemplados no difirieron entre los brazos. Personas que reportaron ser forzados tener sexo, siendo su primer encuentro con sexo anal, tenian CES-D resultados mas altos (Coeff: 3.23; 95 % CI: 1.24 a 5.23) y fueron mas probable contemplar suicidio (OR 2.2; 95 % CI: 1.09 a 4.26). CES-D resultados fueron mas altos en personas reportando recibir penetracion anal sin condon (ncRAI) (OR: 1.46; 95 % CI: 1.09 a 1.94). Recomendamos continuar PrEP durante periodos de depresion, mientras simultaneamente recibir servicios de salud mental.