Miracle-dz/UniFAR-FTUs huggingface dataset:
Idazoxan, an alpha‐2 antagonist, and L‐DOPA‐induced dyskinesias in patients with Parkinson's disease

Dyskinesia is a frequent and disabling side effect in patients with Parkinson's disease treated with chronic dopatherapy. Preclinical data in the 1‐methyl‐4‐phenyl‐1,2,3,6,‐tetrahydropyridine (MPTP) monkey suggest that alpha‐2 antagonists may reduce dihydroxyphenylalanine (L‐DOPA)‐induced dyskinesia. We assessed, in a pilot randomised placebo‐controlled study, the effects of single oral doses (10 mg, 20 mg, and 40 mg) of idazoxan, an alpha‐2 antagonist, on motor parkinsonian disability and L‐DOPA‐induced dyskinesia following an acute oral challenge of L‐DOPA in 18 patients with Parkinson's disease. The severity of L‐DOPA‐induced dyskinesia improved after 20 mg idazoxan pretreatment, while there was no concommittant deterioration in the antiparkinsonian response to L‐DOPA. These results suggest that blocking alpha‐2 receptors in patients with Parkinson's disease might improve L‐DOPA‐induced dyskinesia without the cost of a return of parkinsonian symptomatology. Further studies are required to assess whether this property could have potential therapeutic applications in the long‐term management of dyskinetic patients with Parkinson's disease. © 2001 Movement Disorder Society.
Vaginal estrogens for the treatment of dyspareunia.

INTRODUCTION Vaginal atrophy, which is associated with vaginal itching, burning, dryness, irritation, and pain, is estimated to affect up to 40% of postmenopausal women. Estrogens play a key role in maintaining vaginal health; women with low serum estradiol are more likely to experience vaginal dryness, dyspareunia, and reduced sexual activity compared with women who have higher estradiol levels. AIMS The purpose of this review is to assess the prevalence and impact of dyspareunia, a symptom of vaginal atrophy, on the health of postmenopausal women and to evaluate treatment options using vaginal estrogens (U.S. Food and Drug Administration [FDA] approved). METHODS Relevant published literature was identified by searching Index Medicus using the PubMed online database. The search terms dyspareunia, vaginal estrogen, vaginal hormone therapy, vaginal atrophy, and atrophic vaginitis were the focus of the literature review. RESULTS Current treatment guidelines for vaginal atrophy recommend the use of minimally absorbed local vaginal estrogens, along with non-hormonal lubricants or moisturizers, coupled with maintenance of sexual activity. Vaginal estrogen therapy has been shown to provide improvement in the signs and symptoms of vaginal or vulvar atrophy. Vaginal tablets, rings, and creams are indicated for the treatment of vaginal atrophy, and the FDA has recently approved a low-dose regimen of conjugated estrogens cream to treat moderate-to-severe postmenopausal dyspareunia. The use of low-dose vaginal estrogens has been shown to be effective in treating symptoms of vaginal atrophy without causing significant proliferation of the endometrial lining, and no significant differences have been seen among vaginal preparations in terms of endometrial safety. CONCLUSION Women should be informed of the potential benefits and risks of the treatment options available, and with the help of their healthcare provider, choose an intervention that is most suitable to their individual needs and circumstances.
Correlation between the percentage of body fat and surrogate indices of obesity among adult population in rural block of Haryana

Introduction: The increasing prevalence of overweight and obesity has raised concerns regarding the importance of different techniques, which are used to assess body growth composition that can be used at the level of primary health care settings with minimal knowledge. The purpose of this study was to evaluate the relationship between different surrogate indices of fatness (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], waist-to-height ratio [WHtR], and body fat percentage [BF%]) with the percentage of body fat and their usefulness as a predictor of obesity among adult population. Materials and Methods: The community-based cross-sectional study done over a period of 1-year involved 1080 adult participants from a rural area in Haryana. Anthropometry, along with BF% (using hand held analyzer) were recorded using standard procedures. Results: The prevalence of overweight and obesity as per the modified criteria of BMI for the Asian Indians was found to be 15.0% and 34.6%, respectively. Positive correlation was seen among all the indices except between the WHR and body adiposity index (BAI) using Pearson's correlation analysis. Maximum correlation was seen between WHtR and WC (r = 0.923), whereas WHtR depicted maximum correlation (r = 0.810) with BF%. Receiver operating characteristic curve analysis revealed that the WHtR was the most sensitive and specific indicator for the study population to predict overweight and obesity comparable to that calculated by body fat analyser followed by BAI, BMI, and WHR. Conclusion: A single value of WHtR irrespective of gender and the area of residence can be used as a universal screening tool for the identification of individuals at high risk of development of metabolic complications.
Two Variable Sodium Profiles and Adverse Effects During Hemodialysis: A Randomized Crossover Study

Intradialytic symptomatic hypotension and muscle cramps are frequent and disturbing adverse effects involving hemodialysis patients. The use of sodium profiling has been a proposed approach to preclude such events. The aim of the study was to compare the frequency of intradialytic adverse effects and changes in anthropometric and physiological variables without profiling and with two distinct sodium profiles. A prospective study randomized 22 stable hemodialysis patients to receive either a step (11 patients) or a linear (11 patients) dialysate sodium profile for 12 consecutive sessions, following a 12‐session steady sodium control period. After a wash‐out period of 12 sessions, the groups were crossed over for another 12‐session period. Frequency of adverse effects, interdialytic weight gain, pre‐ and post‐dialysis blood pressure were computed. The frequency of intradialytic adverse effects was significantly different between the control and either the step or linear periods (48.5%, 33.7%, and 36.0%, respectively; P < 0.001). No significant differences in interdialytic weight gain or pre‐dialysis blood pressure were detected between treatment periods. The mean post‐dialysis systolic blood pressure was lower in the linear period (128 ± 21; 127 ± 20; 123 ± 22 mm Hg, for the control, step and linear periods, respectively; P = 0.014). Seven patients benefited from sodium profiling, yet two became more symptomatic. Overall, both sodium profiles were associated with fewer intradialytic adverse effects. Intradialytic symptomatic hypotension occurred less often with the step profile, while a tendency to fewer cramps was associated with the linear profile. However, sodium profiling may not benefit every dialysis patient and should be individually evaluated.
Rasch Analysis of Visual Function and Quality of Life Questionnaires

Purpose. To investigate the psychometric properties of the Visual Function (VF) and Quality of Life (QOL) questionnaires, using the Rasch measurement model. Methods. Four hundred eighty-nine patients with cataract awaiting surgery, drawn from the surgical waiting list of the Flinders Medical Centre, Adelaide, South Australia, were mailed the VF and QOL questionnaires for self-administration. Rasch analysis was undertaken to assess the following properties: measurement of a single construct (i.e., unidimensionality by fit statistics and principal components analysis), discrimination between strata of participant ability (person separation, recommended minimum value 2.0), targeting of item difficulty to participant ability, and differential item functioning (DIF, whether items function similarly for different subgroups and notable DIF defined as >1.0 logit). Results. The VF questionnaire fit the Rasch model showing good metric properties, including unidimensionality, and was free of notable DIF. The QOL questionnaire showed inadequate person separation, two misfitting items and significant multidimensionality (Eigenvalue of 2.3 for the first contrast), suggesting the presence of a separate subscale, self-care, but this was not valid because of inadequate person separation. Deleting these contrasting items from the QOL questionnaire removed multidimensionality and item misfit but did not improve person separation, indicating that it could not effectively discriminate between the participant’s QOL. Both VF and QOL questionnaires demonstrated poor targeting (−2.22 and −3.26 logits, respectively), indicating that items were too easy and participants had higher QOL than that the items allowed for. Three items in the QOL questionnaire demonstrated notable DIF by age and systemic comorbidity. None of the subscales functioned optimally. Conclusions. The QOL questionnaire is not a valid measure of QOL. However, the VF questionnaire is a reliable and valid measure of visual disability in patients with cataract, and although targeting was suboptimal in a developed country, it may be optimal in a developing country as was originally intended.
Differential regulation by glucose and fructose of a gene encoding a specific fructose/H+ symporter in Saccharomyces sensu stricto yeasts

Saccharomyces cerevisiae transports fructose through a facilitated diffusion system common to other hexoses and mediated by the Hxt proteins. The related species S. pastorianus (carlsbergensis) and S. bayanus produce, in addition, a specific fructose/H+ symporter. We have previously cloned a gene (FSY1) encoding the active fructose symporter from S. pastorianus PYCC 4457. Expression of Fsy1p in a S. cerevisiae mutant (hxt‐null) devoid of the facilitated diffusion system allows growth on fructose but not on glucose. Here we present results concerning the regulation of Fsy1p expression, both in S. pastorianus and S. bayanus, where it occurs naturally, and in suitably engineered S. cerevisiae transformants. To that purpose, we made use of both Northern blot analysis and a Fsy1p–GFP fusion protein. The expression of Fsy1p is strongly regulated by both the carbon source and its concentration in the growth medium. In S. pastorianus, as well as in S. bayanus, very low concentrations of either fructose or glucose induced expression but higher sugar concentrations prevented transcription of the gene. Glucose was considerably more effective than fructose in repressing FSY1 expression. Proper regulation of the gene in S. cerevisiae seems to be exquisitely dependent on sugar transport. Analysis of Fsy1 expression in S. cerevisiae mutants shows that repression is mainly dependent on Mig1p, the final effector of the main glucose repression pathway. Interestingly, Mig1p also seems to mediate repression of FSY1 expression by high maltose concentrations. Copyright © 2004 John Wiley & Sons, Ltd.
Inhibition of acid ceramidase by a 2‐substituted aminoethanol amide synergistically sensitizes prostate cancer cells to N‐(4‐hydroxyphenyl) retinamide

The purpose of this study was to determine whether the therapeutic efficacy of fenretinide (4‐HPR), a ceramide‐generating anticancer agent, could be enhanced in prostate cancer cells by inclusion of a novel synthetic acid ceramidase (AC) inhibitor, DM102, a pivaloylamide of a 2‐substituted aminoethanol. In prostate cancer, AC plays a role in progression and resistance to chemotherapy.
Striking a Balance Between the Risks and Benefits of Anticoagulation Bridge Therapy in Patients with Atrial Fibrillation: Clinical Updates and Remaining Controversies

Long‐term anticoagulation with a vitamin K antagonist (VKA) or the new agent dabigatran is recommended to decrease stroke risk in patients with atrial fibrillation. When patients with atrial fibrillation undergo initiation or interruption of VKA therapy, or experience an isolated subtherapeutic international normalized ratio (INR), bridge therapy with a parenteral anticoagulant may be considered. To describe the literature for anticoagulation bridge therapy in patients with atrial fibrillation, we conducted a MEDLINE search (1966–February 2011) of the English‐language literature to identify related studies. Ongoing clinical trials were identified through a search of the ClinicalTrials.gov registry. Major national and international guidelines were gathered and evaluated. Additional literature was obtained through review of relevant references of the identified articles. Bridging is not supported by guidelines or clinical trials for patients starting VKA therapy for atrial fibrillation. A subtherapeutic INR value during long‐term VKA therapy may be associated with increased thromboembolic events, but the benefit of bridging has not been demonstrated. When VKA therapy is interrupted for procedures, retrospective and cohort data suggest that the decision to bridge should be based on a patient's thromboembolic and bleeding risks associated with the procedure. Typically, it is recommended to use bridge therapy in patients with atrial fibrillation at high risk for thromboembolism, but the benefit of bridging is less clear in patients at low risk. Not all procedures necessitate anticoagulation interruption. Recent trials suggest that VKAs can be continued when patients are undergoing cardiac device procedures and some types of radiofrequency ablation. Several clinical trials are ongoing that will provide more definitive guidance for perioperative anticoagulation management of patients with atrial fibrillation. Patients taking dabigatran are unlikely to require bridge therapy because of a predictable anticoagulant effect and rapid onset of action. However, evidence for optimal perioperative management of dabigatran is needed.
Association of XRCC3 Thr241Met polymorphisms and gliomas risk: evidence from a meta-analysis.

UNLABELLED The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met polymorphism and gliomas remains inclusive or controversial. For better understanding of the effect of XRCC3 Thr241Met polymorphism on glioma risk, a meta-analysis was performed. All eligible studies were identified through a search of PubMed, Elsevier Science Direct, Excerpta Medica Database (Embase) and Chinese Biomedical Literature Database (CBM) before May 2013. The association between the XRCC3 Thr241Met polymorphism and gliomas risk was conducted by odds ratios (ORs) and 95% confidence intervals (95% CIs). A total of nine case-control studies including 3,533 cases and 4,696 controls were eventually collected. Overall, we found that XRCC3 Thr241Met polymorphism was significantly associated with the risk of gliomas (T vs. C: OR=1.10, 95%CI=1.01-1.20, P=0.034; TT vs. CC: OR=1.30, 95%CI=1.03-1.65, P=0.027; TT vs. TC/CC OR=1.29, 95%CI=1.01-1.64, P=0.039). In the subgroup analysis based on ethnicity, the significant association was found in Asian under four models (T vs. C: OR=1.17, 95%CI=1.07-1.28, P=0.00; TT vs. CC: OR=1.79, 95%CI=1.36- 2.36, P=0.00; TT vs. TC/CC OR=1.75, 95%CI=1.32-2.32, P=0.00; TT/TC vs. CC: OR=1.11,95% CI=1.02-1.20). This meta-analysis suggested that the XRCC3 Thr241Met polymorphism is a risk factor for gliomas, especially for Asians. Considering the limited sample size and ethnicities included in the meta-analysis, further large scale and well-designed studies are needed to confirm our results.
Comparison of Two HIV Postexposure Prophylaxis Regimens Among Men Who Have Sex With Men in Amsterdam: Adverse Effects Do Not Influence Compliance

Objectives: To compare 2 regimens for HIV postexposure prophylaxis (PEP) as to safety, adherence, outcome, and follow-up in men who have sex with men (MSM) in Amsterdam. Methods: Since 2000, all MSM starting HIV PEP in Amsterdam have been followed in 1 location. The regimen was comprised of zidovudine or lamivudine and nelfinavir (regimen 1) until 2005, when nelfinavir was replaced by atazanavir (regimen 2). All patient data, including data on PEP side effects and testing for alanine aminotransferase (ALT), were systematically recorded and compared between the 2 regimens from 2000 to 2007. Results: HIV PEP was prescribed 309 times to MSM. Of the 261 who were followed up, 237 (91%) completed their 28-day course. Although fewer patients had diarrhea on regimen 2 than on regimen 1 (P = 0.00), the proportion completing either course was the same: 98 of 110 (89%) and 139 of 151 (92%), respectively (P = 0.42). Only 1 patient with severely elevated ALT was advised to stop PEP, he also had serious illness. MSM at least 30 years of age and MSM who had sex with a partner known to be HIV-positive completed their course significantly more often than those under 30 and those who had sex with a partner of unknown HIV status (P < 0.005). Of MSM who completed PEP, 5 seroconverted for HIV despite good adherence to PEP. None of their viruses were resistant to the PEP regimen used. Conclusions: No difference in adherence was found between the 2 regimens, even though fewer adverse effects were reported on regimen 2. ALT need not be routinely tested to monitor adverse effects. The 5 seroconversions were not likely caused by PEP failure, but rather by ongoing HIV exposures.
Changes in muscle activity with increasing running speed

Electromyographic (EMG) activity of the leg muscles and the ground reaction forces were recorded in 17 elite male middle-distance runners, who performed isometric maximal voluntary contractions (MVC) as well as running at different speeds. Electromyograms were recorded from the gluteus maximus, vastus lateralis, biceps femoris, gastrocnemius and tibialis anterior. The results indicated that the averaged EMG (aEMG) activities of all the muscles studied increased (P < 0.05) with increasing running speed, especially in the pre-contact and braking phases. At higher speeds, the aEMG activities of the gastrocnemius, vastus lateralis, biceps femoris and gluteus maximus exceeded 100% MVC in these same phases. These results suggest that maximal voluntary contractions cannot be used as an indicator of the full activation potential of human skeletal muscle. Furthermore, the present results suggest that increased pre-contact EMG potentiates the functional role of stretch reflexes, which subsequently increases tendomuscular stiffness and enhances force production in the braking and/or propulsive phases in running. Furthermore, a more powerful force production in the optimal direction for increasing running speed effectively requires increased EMG activity of the two-joint muscles (biceps femoris, rectus femoris and gastrocnemius) during the entire running cycle.
Gingival crevicular fluid laminin-5 gamma2-chain levels in periodontal disease.

AIM Our study aimed to examine the molecular forms and gingival crevicular fluid (GCF) levels of laminin-5 gamma2-chain in patients with different periodontal disease, and compare the effects of P.gingivalis trypsin-like proteinase on intact laminin-5 gamma2-chain species. METHODS Eighteen patients with generalized aggressive periodontitis (G-AgP), 29 patients with chronic periodontitis (CP), 20 with gingivitis and 20 periodontally healthy subjects were included. Probing depth, clinical attachment loss, presence of bleeding on probing and plaque were recorded. Molecular forms and GCF laminin-5 gamma2-chain levels and the effects of P. gingivalis trypsin-like proteinase on intact laminin-5 gamma2-chain were analysed by computer-quantitated Western immunoblotting. RESULTS Laminin-5 gamma2-chain 40 and 70 kDa fragments could be detected in all groups, in varying levels. The CP group had elevated GCF laminin-5 gamma2-chain fragment levels compared with the gingivitis and healthy groups (p<0.008). The G-AgP group had GCF laminin-5 gamma2-chain fragment levels similar to the gingivitis and healthy groups (p>0.008). GCF laminin-5 gamma2-chain fragments differed clearly from the multiple lower molecular size fragments of P.gingivalis trypsin-laminin-5 gamma2-chain proteinases. CONCLUSION Increased GCF laminin-5 gamma2-chain fragments in periodontitis sites with deep periodontal pocket suggest that these cleaved 40 and 70 kDa fragments could reflect the extent of the inflammatory reaction in CP.
Effect of prepartum energy, body condition, and sodium bicarbonate on production of cows in early lactation.

In trial 1, the effects of dietary energy (102, 131 or 162% of requirement) in the dry period and of sodium bicarbonate (0 or .75% of diet dry matter) in early lactation were assessed with 31 cows in a 3 X 2 factorial arrangement of treatments. Body condition and weight increased linearly with prepartum energy. Dry matter intake and milk yield were similar across treatments through 12 wk postpartum. Sodium bicarbonate increased milk fat content only in the 131% group, an effect apparently related to greater mobilization of fat in that group. In trial 2, energy treatments imposed in late lactation (145 to 55 d prepartum) and in the dry period (55 to 0 d) were 1) cows fed to requirement in both periods, 2) cows overfed in the first and underfed in the second period, 3) cows fed to requirement in the first and overfed in the second period, and 4) cows overfed in both periods. Cows in treatments 1 and 2 (normal) calved in a thinner state than those in 3 or 4 (fat). In the first 12 wk postpartum, intake did not differ, but cows in groups 3 and 4 produced more milk. Sodium bicarbonate imposed factorially postpartum increased milk fat content. Overconsumption of energy prepartum did not impair production when high energy total mixed rations were fed postpartum.
The Chemokine Fractalkine Inhibits Fas-Mediated Cell Death of Brain Microglia

Fractalkine is a CX3C-family chemokine, highly and constitutively expressed on the neuronal cell surface, for which a clear CNS physiological function has yet to be determined. Its cognate receptor, CX3CR-1, is constitutively expressed on microglia, the brain-resident macrophages; however, these cells do not express fractalkine. We now show that treatment of microglia with fractalkine maintains cell survival and inhibits Fas ligand-induced cell death in vitro. Biochemical characterization indicates that this occurs via mechanisms that may include 1) activation of the phosphatidylinositol-3 kinase/protein kinase B pathway, resulting in phosphorylation and blockade of the proapoptotic functions of BAD; 2) up-regulation of the antiapoptotic protein Bcl-xL; and 3) inhibition of the cleavage of BH3-interacting domain death agonist (BID). The observation that fractalkine serves as a survival factor for primary microglia in part by modulating the protein levels and the phosphorylation status of Bcl-2 family proteins reveals a novel physiological role for chemokines. These results, therefore, suggest that the interaction between fractalkine and CX3CR-1 may play an important role in promoting and preserving microglial cell survival in the CNS.