Miracle-dz/UniFAR-FTUs huggingface dataset:
Enzalutamide , anAndrogenReceptor Signaling Inhibitor , InducesTumorRegression in aMouseModel of Castration-Resistant ProstateCancer

BACKGROUND. Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: binding of androgens to AR, AR nuclear translocation, and association of AR with DNA. Here, we investigate the effects of enzalutamide on AR signaling, AR-dependent gene expression and cell apoptosis. METHODS. The expression of AR target gene prostate-specific antigen (PSA) was measured in LnCaP and C4-2 cells. AR nuclear translocation was assessed in HEK-293 cells stably transfected with AR-yellow fluorescent protein. The in vivo effects of enzalutamide were determined in a mouse xenograft model of CRPC. Differential gene expression in LNCaP cells was measured using Affymetrix human genome microarray technology. RESULTS. We found that unlike bicalutamide, enzalutamide lacked AR agonistic activity at effective doses and did not induce PSA expression or AR nuclear translocation. Additionally, it is more effective than bicalutamide at inhibiting agonist-induced AR nuclear translocation. Enzalutamide induced the regression of tumor volume in a CRPC xenograft model and apoptosis in AR-over-expressing prostate cancer cells. Finally, gene expression profiling in LNCaP cells indicated that enzalutamide opposes agonist-induced changes in genes involved in processes such as cell adhesion, angiogenesis, and apoptosis. CONCLUSIONS. These results indicate that enzalutamide efficiently inhibits AR signaling, and we suggest that its lack of AR agonist activity may be important for these effects. Prostate # 2013 Wiley Periodicals, Inc.
Comparison of ocular hypotensive actions of fixed combinations of brimonidine/timolol and dorzolamide/timolol

Abstract Objective: To compare brimonidine/timolol fixed combination (BrTFC; Combigan with dorzolamide/timolol fixed combination (DTFC; Cosopt in terms of ability to lower intraocular pressure (IOP) in primary open-angle glaucoma (POAG). Methods: This was a prospective, randomized, double-masked, crossover study. After 6 weeks of therapy with timolol maleate 0.5% twice daily, patients were randomized to BrTFC twice daily or DTFC twice daily for 6 weeks, before being crossed over to the other treatment arm for a further 6 weeks. At all follow-up visits, IOP was measured at 09.00 (pre-instillation) 12.00 and 16.00. The primary outcome measure was change in mean diurnal IOP from baseline at 6 weeks. The secondary outcome was percentage of patients with IOP <18 mmHg at 6 weeks. Data were analyzed from all patients who completed the study. Results: Twenty-five patients were randomized and 20 completed the study. Mean diurnal IOP (mean ± standard deviation [SD]) was 20.28 ± 2.03 mmHg at timolol-treated baseline. After 6 weeks, mean diurnal IOP was 16.28 ± 2.07 mmHg following BrTFC and 17.23 ± 2.29 mmHg following DTFC (difference: 0.95 mmHg, 95% CI 0.10–1.80, p = 0.03). Mean IOP at 09.00 was 20.95 ± 2.31 mmHg at baseline. This was reduced to 15.85 ± 2.56 mmHg following BrTFC and 17.55 ± 2.67 mmHg following DTFC (difference: 1.70, 95% CI 0.80–2.60, p = 0.001). For the 12.00 and 16.00 timepoints, the mean changes from baseline in the two arms were comparable. Percentages of patients achieving a target IOP of <18 mmHg were 85% following BrTFC and 60% following DTFC (p = NS [not significant]). No treatment-related adverse events were reported with either therapy. Key limitations include the small size of the study population and the 6-week duration of treatment periods, which prevents drawing conclusions regarding long-term therapy. Conclusion: Reductions from baseline in mean diurnal IOP and morning IOP were greater with BrTFC than with DTFC.
A Meta-Analysis of Antibiotics Versus Surgery for the Treatment of Acute Appendicitis

Appendectomy is the mainstay of treatment for acute appendicitis. Considering the complications of surgery, antibiotic treatment has also been gaining increasing interest in cases of acute appendicitis. This study aimed to compare the efficacy of antibiotics to surgery for acute uncomplicated appendicitis. The PubMed, Medline, Medscape and Cochrane databases were searched for studies comparing antibiotics versus surgery. The six outcome measures identified were thirty-day post-therapeutic peritonitis, length of hospital stay, prevalence of total complications, prevalence of normal appendix, prevalence of mean duration of pain and duration of disability. Five prospective RCTs with a total of 1430 patients (644 in the antibiotic group and 786 in the surgical group) were included in this study. Antibiotic treatment had a success rate of 75.3%. Regarding overall mean duration of disability, the antibiotic group had a significantly shorter duration of disability than that of the surgery group (P 0.05). Although the conservative approach has a success rate lower than appendectomy, it is a possible alternative in certain clinical scenarios. Appendectomy remains the mainstay treatment for acute appendicitis. However, additional studies clarifying the certain etiologies of appendicitis that are responsive to antibiotic treatment are needed to further support its use.
Diagnosis and Treatment of Fractures of the Talus: A Comprehensive Review of the Literature

Fractures of the head, neck, and body of the talus present difficult treatment challenges. The vulnerable blood supply and abundant articular surfaces may lead to long-term problems with osteonecrosis and osteoarthrosis. Previous studies of these relatively rare injuries have been mostly small, inconsistent, or anecdotal, leading to confusion and controversy regarding the optimum treatment of various types of talus fractures. The surgeon who treats these injuries must be prepared to address meticulous reduction and fixation, maintain attentive follow-up, and manage the complications that may result despite appropriate treatment. This review summarizes the findings of the literature on each type of talus fracture to provide a clearer picture of their recommended management.
Perception by Osseointegrated Dental Implants Supporting a Fixed Prosthesis: A Prospective Study.

PURPOSE Osseointegrated implants have been shown to transmit a certain sensibility termed as osseoperception. The purpose of this study was to determine the perception by implants over a period of 6 months after loading in comparison to the natural dentition. MATERIALS AND METHODS Twenty subjects (ages 40 to 50 years) were included in this split-mouth clinical trial. The subjects were divided into two groups (n = 10) as follows: group 1-subjects with recently cemented implant-supported fixed prosthesis opposing natural teeth; group 2-subjects with recently cemented implant-supported fixed prosthesis in both arches. The implant-supported prostheses were considered as the test sites, whereas natural teeth on the contralateral side were considered as the control. Articulating papers of varied thickness were placed interocclusally in the posterior region in a predetermined random order of true and false insertions. The subjects' ability to perceive the presence/absence of the test papers was recorded for every insertion. The evaluation was performed immediately after cementation and at 1 week, 3 months, and 6 months after cementation. The minimum interocclusal thickness detected by the subjects at the test and control sites at different time intervals was used for further analysis. RESULTS All subjects with implant-supported prostheses perceived a certain thickness of articulating paper. The minimum interocclusal thickness detected by the implant-supported prosthesis decreased postloading; however, the difference was not statistically significant (P > .008). At the end of the follow-up period, the minimum interocclusal thickness detected by the implants in group 1 was similar to the controls, whereas it was significantly higher than the controls in group 2 (P < .05). CONCLUSION There was progressive improvement in the perception by implant-supported prostheses during the follow-up period, and it was nearing the perception by natural teeth in subjects with implants opposing natural teeth.
rTMS Combined With Task-Oriented Training to Improve Symmetry of Interhemispheric Corticomotor Excitability and Gait Performance After Stroke

Background. The model of interhemispheric competition after stroke has been established for the upper but not for the lower extremity. Repetitive transcranial magnetic stimulation (rTMS) of the brain has been shown to modulate cortical excitability. Objective. The purpose of this study was to investigate the effects of rTMS followed by task-oriented training on cortical excitability and walking performance in individuals with chronic stroke. Methods. A total of 24 patients with average Fugl-Meyer lower limb scores of 17.88 ± 5.27 and average walking speeds of 63.81 ± 18.25 cm/s were randomized into an experimental group and a control group. Participants received rTMS (experimental group) or sham rTMS (control group) followed by task-oriented training (30 minutes) for 10 sessions over 2 weeks. Repetitive TMS was applied at a 1-Hz frequency over the leg area of the motor cortex of the unaffected hemisphere for 10 minutes. Outcomes, including motor-evoked potential (MEP), lower-extremity Fugl-Meyer score, and gait performance, were measured before and after training. Results. Decreased interhemispheric asymmetry of the amplitude of the MEP was noted after rTMS and task-oriented training. Improvement in spatial asymmetry of gait was comparable with increased symmetry in interhemispheric excitability. Motor control and walking ability were also significantly improved after rTMS and task-oriented training. Conclusions. rTMS enhances the effect of task-oriented training in those with chronic stroke, especially by increasing gait spatial symmetry and corticomotor excitability symmetry.
Caffeine Neuroprotective Mechanism Against β-Amyloid Neurotoxicity in SHSY5Y Cell Line: Involvement of Adenosine, Ryanodine, and N-Methyl-D-Aspartate Receptors

Purpose: Some reports have shown neuroprotective effects of caffeine in several neurodegenerative disorders. However, its mechanism of action is not completely clear. Therefore, the aim of this study was to explore the interference of ryanodine, N-methyl-D-aspartate (NMDA) and adenosine modulators with the neuroprotective effects of caffeine against β-amyloid (Aβ) neurotoxicity in the SHSY5Y cells. Methods: The SHSY5Y cells were treated with Aβ23-35 (20µM) and/or caffeine (0.6 and 1mM), or both for 24 hours. Adenosine (20, 40, 60, 80, 100µM), NMDA (20, 50, 70, 90µM), dantrolene (2, 4, 6, 8, 10µM) were also added to the medium and incubated for 24 hours. The cell viability was measured via the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) method. The data were analyzed using one-way ANOVA followed by Bonferroni test. Results: Caffeine at all the used concentrations (0.6, 0.8, 0.9, 1, and 3mM) significantly protected neuronal cells against Aβ neurotoxicity. Adenosine at the concentrations of 20, 40, 80 and 100μM diminished the neuroprotective effects of caffeine (0.6 and 1mM) against Aβ neurotoxicity. NMDA at the concentrations of 20, 50, 70 and 90μM blocked caffeine (0.6 and 1mM) neuroprotective effects. Dantrolene at the concentration of 2, 4, 6, 8 and 10μM diminished the neuroprotective effects of caffeine (0.6mM) and at the concentrations of 2 and 10μM impede caffeine (1mM) neuroprotection against Aβ neurotoxicity. Conclusion: Caffeine produced neuroprotective effect against Aβ neurotoxicity. Blockade of adenosine and NMDA receptors, as well as the activation of ryanodine receptors, may contribute to the neuroprotective effects of caffeine.
HORMONES AND CHOLESTEROL ESTER METABOLISM

A study was made of the effects of testosterone, estradiol, ACTH, insulin, epinephrine and l‐thyroxine on a microsomal preparation of female rat liver esterifying enzyme and cholesterol plus palmitic, oleic and linoleic acids. In the doses used, these hormones modified the rate of ester synthesis. Further experiments showed that low doses of androgen or estrogen had a stimulating effect whereas high doses had an inhibitory effect.
Nationwide Surveillance Study of Clostridium difficile in Australian Neonatal Pigs Shows High Prevalence and Heterogeneity of PCR Ribotypes

ABSTRACT Clostridium difficile is an important enteric pathogen of humans and the cause of diarrhea and enteritis in neonatal pigs. Outside Australia, prevalence in piglets can be up to 73%, with a single PCR ribotype (RT), 078, predominating. We investigated the prevalence and genotype of C. difficile in Australian pig herds. Rectal swabs (n = 229) were collected from piglets aged <7 days from 21 farms across Australia. Selective culture for C. difficile was performed and isolates characterized by PCR for toxin genes and PCR ribotyping. C. difficile was isolated from 52% of samples by direct culture on chromogenic agar and 67% by enrichment culture (P = 0.001). No association between C. difficile recovery or genotype and diarrheic status of either farm or piglets was found. The majority (87%; 130/154) of isolates were toxigenic. Typing revealed 23 different RTs, several of which are known to cause disease in humans, including RT014, which was isolated most commonly (23%; 36/154). RT078 was not detected. This study shows that colonization of Australian neonatal piglets with C. difficile is widespread in the herds sampled.
Frequency modulation of Ca sparks is involved in regulation of arterial diameter by cyclic nucleotides

W. J. Frequency modulation of Ca 2 (cid:49) sparks is involved in regulation of arterial diameter by cyclic nucleotides. Am. J. Physiol. 274 ( Cell Physiol. 43): C1346–C1355, 1998. —Forskolin, which elevates cAMP levels, and sodium nitroprusside (SNP) and nicorandil, which elevate cGMP levels, increased, by two- to threefold, the frequency of subcellular Ca 2 (cid:49) release (‘‘Ca 2 (cid:49) sparks’’) through ryanodine-sensitive Ca 2 (cid:49) release (RyR) channels in the sarcoplasmic reticulum (SR) of myocytes isolated from cerebral and coronary arteries of rats. Forskolin, SNP, nicorandil, dibutyryl-cAMP, and adenosine increased the frequency of Ca 2 (cid:49) -sensitive K (cid:49) (K Ca ) currents [‘‘spontaneous transient outward currents’’ (STOCs)] by two- to threefold, consistent with Ca 2 (cid:49) sparks activating STOCs. These agents also increased the mean amplitude of STOCs by 1.3-fold, an effect that could be explained by activation of K Ca channels, independent of effects on Ca 2 (cid:49) sparks. To test the hypothesis that cAMP could act to dilate arteries through activation of the Ca 2 (cid:49) spark = K Ca channel pathway, the effects of blockers of K Ca channels (iberiotoxin) and of Ca 2 (cid:49) sparks (ryanodine) on forskolin-induced dilations of pressurized cerebral arteries were examined. Forskolin-induced dilations were partially inhibited by iberiotoxin and ryanodine (with no additive effects) and were entirely prevented by elevating external K (cid:49) . Forskolin lowered average Ca 2 (cid:49) in pressurized arteries while increasing ryanodine-sensitive, caffeine-induced Ca 2 (cid:49) transients. These experiments suggest a new mechanism for cyclic nucleotide-mediated dilations through an increase in Ca 2 (cid:49) spark frequency, caused by effects on SR Ca 2 (cid:49) load and possibly on the RyR channel, which leads to increased STOC frequency, membrane potential hyperpolarization, closure of voltage-dependent Ca 2 (cid:49) channels, decrease in arterial wall Ca 2 (cid:49) , and, ultimately, vasodilation.
Epidemiology of perinatal stroke

Perinatal stroke has become increasingly recognized, but the incidence is probably underestimated because of variation in the presentation, evaluation, and diagnosis. Based on estimates from population-based studies of infants with seizures, perinatal stroke occurs in approximately 1 in 4000 term births. Most perinatal strokes involve the middle cerebral artery and are caused by thromboembolism from an intracranial or extracranial vessel, the heart, or the placenta. Cardiac disorders, coagulation abnormalities, and infection are risk factors for stroke in the perinatal period. This article discusses the epidemiology of ischemic stroke occurring in the perinatal and neonatal period, including cerebrovascular events that are diagnosed during the perinatal period and those diagnosed retrospectively, when evidence of hemiparesis or postneonatal seizures leads to later evaluation and neuroimaging.
Mitochondrial polarization in rat hippocampal astrocytes is resistant to cytosolic Ca2+ loads

The influence of physiological Ca2+‐inducing stimuli and agents mimicking ischemic conditions on mitochondrial potential was studied in postnatal (P1) hippocampal astrocytes. Cytosolic Ca2+ loads with characteristic kinetics of rise and duration, detected by Fura‐2, were provoked by extracellular Ca2+ influx, release from InsP3‐sensitive intracellular stores, or inhibition of the reloading of endoplasmic reticulum Ca2+ stores. Inhibitors of mitochondrial respiration caused only moderate release of Ca2+ from intracellular stores, inducing a rise of less than 60 nM. The maximal Ca2+ rise was found with InsP3‐mediated responses (500 nM; via ATP) or with ionophore (4‐Br‐A23187)‐mediated Ca2+ influx from extracellular medium (770 nM). Remarkably, all these agents causing significant rise of cytosolic Ca2+, only minimally depolarized the mitochondria. Membrane potential of mitochondria was monitored by Rh123 or TMRE. Depolarization was only found with very high cytosolic Ca2+ levels (above 60 μM; measured by fura FF). These were achieved with external Ca2+ influx by ionophore in combination with inhibition of glycolysis. Thus, mitochondria in the astrocytes are obviously not sensitive to moderate cytosolic Ca2+ loads, irrespective of the source of Ca2+. Furthermore, isolated rat brain mitochondria display a low sensitivity of respiratory activity to Ca2+, which is consistent with the data obtained with the astrocytes in vitro. The capacity of isolated mitochondria to build up a potential was gradually reduced at low micromolar Ca2+ and totally compromised only at Ca2+ concentrations in the 100 μM range. © 2001 Wiley‐Liss, Inc.
Basal metabolic rate is correlated with blood pressure among young population

Backgrounds: Our study was to confirm the positive relationship of predicted basal metabolic rate (BMR) and blood pressure (BP) and to determine if BMR was still predictive, irrespective of demographic and anthropometric variables in young Chinese population. Methods: BP measurements were performed by trained workers through a standardized method using Omron HE: 7071 electronic sphygmomanometer. BMR values were calculated by a given formula of Omron HBF-306 Body Fat Monitor. Results: The mean systolic blood pressures (SBP) and diastolic blood pressures (DBP) as well as pulse pressure (PP) increased with increasing BMR deciles (SBP by 20 mmHg, DBP by 4 mmHg and PP by 15 mmHg from the 1st decile to the 5th decile, Ptrends<0.001 for all). Pearson correlation analyses indicated that BMR was positively correlated with SBP (r=0.601, P<0.001), DBP (r=0.243, P<0.001) and PP (r=0.588, P<0.001). After adjusting with potential confounding factors, the regression coefficients indicated that every 1 Kcal/day higher BMR level was associated with an increase of 0.021 mmHg SBP (P<0.001), 0.008 mmHg DBP (P<0.001) and 0.013 mmHg PP (P<0.001). This did not alter substantially after further adjustment for waist circumference. In addition, we also found that the relationship between BMR and BP did not materially change, particularly for SBP and PP, after using a series of equations for BMR calculation. Conclusions: The study showed that the predicted BMR might be a good metabolic surrogate to predict the development of high blood pressure considering its simplicity and feasibility in clinical practices.
Morning headache in habitual snorers: Frequency, characteristics, predictors and impacts

Objectives: Morning headache has been considered as an accompanying symptom of obstructive sleep apnoea syndrome (OSAS). However the frequency, characteristics, predictors and impacts of morning headache in habitual snorers are not well defined. Methods: We studied consecutive patients with habitual snoring in a sleep laboratory using polysomnography. All patients were interviewed by a physician regarding the presence or absence of morning headache, migraine and insomnia. Each patient completed the Short Form-36 health survey (SF-36) and the Hospital Anxiety and Depression Scale (HADS). Morning headache was defined as headache on awakening ≥1 day/week for ≥6 months. Results: Of the 268 participants with habitual snoring, 63 (23.5%) had morning headache and 184 (69%) had OSAS. Patients with morning headache reported lower scores in all eight domains of the SF-36 than those without (difference: 10.6 to 29.7 points, all p ≤ 0.005). The independent predictors of morning headache were migraine (adjusted odds ratio (AOR) 6.3), insomnia (AOR 4.2), psychological distress (HADS ≥ 8) (AOR 3.9) and OSAS (AOR 2.6). Morning headache in 12 patients (19%) fulfilled the criteria for migraine attacks. Conclusions: Morning headache was common in habitual snorers and associated with a pervasive impairment of health-related quality of life. Migrainous features were not uncommon. Not only OSAS, but migraine, insomnia and psychological distress were also important predictors for morning headache, even in snoring patients.
Learning: What and How? An Empirical Study of Adjustments in Workplace Organization Structure

We seek to understand how firms learn about what adjustments they need to make in their organization structure at the workplace level. We define four organizational systems: traditional (the simplest system), high-performance (the most complex system), decision-making oriented, and financial-incentives oriented (intermediate complexity). We analyze (1) learning-by-doing on adoption of more or less complex systems, (2) the performance-experience learning curves associated with different systems, (3) the match between perceived organizational capabilities and the choice of systems, the influence of (4) other firms systems and performance on a firms adjustment decisions, and of (5) a firms location on its decisions.
Ductal carcinoma in situ diagnosed with stereotactic core needle biopsy: can invasion be predicted?

PURPOSE To determine whether mammographic or histologic features can be used to predict which cases diagnosed as ductal carcinoma in situ (DCIS) without invasion by means of stereotactic core needle biopsy (SCNB) will have invasive disease at surgery. MATERIALS AND METHODS From July 1992 to March 1999, DCIS without invasion was diagnosed by means of SCNB in 59 patients. Seventeen (29%) were found to have invasive disease after surgery. The underestimation rate for SCNB was compared with that obtained by means of open surgical biopsy. Mammographic and histologic features of cases with and those without invasion were compared. RESULTS All patients had calcifications on mammograms. There was no significant difference (P: =.26) between the underestimation rate for SCNB with the 11-gauge vacuum-assisted device and that for open surgical biopsy. No statistically significant differences between cases with and those without invasion were seen in patient age, mean number of core specimens, level of suspicion, size of lesion, distribution and morphology of the calcifications, presence of an associated mass or density, subtype of DCIS, nuclear grade, or presence of necrosis or desmoplasia. CONCLUSION Mammographic and histologic features cannot be used reliably to predict cases that are underestimated with SCNB. However, SCNB with the 11-gauge vacuum-assisted device was as reliable as open surgical biopsy for diagnosing DCIS without invasion.