Recently, we demonstrated that two members of neurotrophins, nerve growth factor and brain-derived neurotrophic factor, and two types of receptor, tyrosine kinase A (TrkA) and tyrosine kinase (TrkB), exist in ejaculated bull spermatozoa, and play a crucial role in the normal function of spermatozoa. Neurotrophin-4 (NT-4) is another neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase, and no reports of detection of NT-4 in spermatozoa have been published. In the present study, the presence of NT-4 in mature bull spermatozoa was investigated using RT-PCR, immunofluorescence and Western blotting. The result shows that there was no RT-PCR evidence for NT-4 transcripts in bovine spermatozoa. However, the NT-4 protein was present in bovine spermatozoa, and the NT-4 immunoreactivity was localized to the equatorial segment and midpiece of bovine spermatozoa. In addition, effects of NT-4 on function of spermatozoa were studied. Significant increased mitochondria activity of mature bovine spermatozoa was observed in response to 300 or 500 ng/ml exogenous NT-4 (p < 0.05), in comparison with the control, while addition of inhibitors (40 ng/ml k252α) specific for tyrosine protein kinase significantly blocked the increase of mitochondria activity. However, NT-4 had no effects on the viability or acrosome reaction of spermatozoa (p > 0.05). Consequently, this study provided evidence that NT-4 protein was presented in the mature bull spermatozoa and can influence the mitochondrial activity of bovine spermatozoa through TrkB tyrosine kinase-dependent pathways.

Osmotic disruption of the blood brain barrier (BBB) by intraarterial mannitol injection is sometimes the key step for the delivery of chemotherapeutic drugs to brain tissue. BBB disruption (BBBD) with mannitol, however, can be highly variable and could impact local drug deposition. We use optical pharmacokinetics, which is based on diffuse reflectance spectroscopy, to track in vivo brain tissue concentrations of indocyanine green (ICG), an optical reporter used to monitor BBBD, and mitoxantrone (MTX), a chemotherapy agent that does not deposit in brain tissue without BBBD, in anesthetized New Zealand white rabbits. Results show a significant increase in the tissue ICG concentrations with BBBD, and our method is able to track the animal-to-animal variation in tissue ICG and MTX concentrations after BBBD. The tissue concentrations of MTX increase with barrier disruption and are found to be correlated to the degree of disruption, as assessed by the ICG prior to the injection of the drug. These findings should encourage the development of tracers and optical methods capable of quantifying the degree of BBBD, with the goal of improving drug delivery.

Triptolide(CAS 38748-32-2), a major active component of Tripterygium wilfordii Hook F (TWHF), is known to have multiple pharmacological activities. However, studies have also shown that triptolide is highly disrupt to the reproductive system by disrupting normal steroid hormone signaling. In the present study, we investigated the effect of triptolide (5, 10, or 20 nM for 24 h) on progesterone production by rat granulosa cells. Triptolide inhibited both basal and human chorionic gonadotropin (HCG)- and 8-bromo-cAMP-stimulated progesterone production as revealed by RIA assay. Furthermore, the HCG-evoked increase in cellular cAMP content was also inhibited by triptolide, indicating that disruption of the cAMP/PKA signaling pathway may mediate the deleterious effects of triptolide on progesterone regulation. In addition, triptolide inhibited 25-OH-cholesterol-stimulated progesterone production, suggesting that activity of the P450 side chain cleavage (P450scc) enzyme was also be inhibited by triptolide. Western blot and quantitative real-time PCR (qRT-PCR) assays further revealed that triptolide decreased mRNA and protein expression of P450scc and the steroidogenic regulatory (StAR) protein in granulosa cells. In contrast, cell viability tests using 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) indicated that triptolide did not cause measurable cell death at doses that suppressed steroidogenesis. The reproductive toxicity of triptolide may be caused by disruption of cAMP/PKA-mediated expression of a number of progesterone synthesis enzymes or regulatory proteins, leading to reduced progesterone synthesis and reproductive dysfunction.

The χ_{b}(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider at sqrt[s]=7  TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4  fb^{-1}, these states are reconstructed through their radiative decays to Υ(1S,2S) with Υ→μ^{+}μ^{-}. In addition to the mass peaks corresponding to the decay modes χ_{b}(1P,2P)→Υ(1S)γ, a new structure centered at a mass of 10.530±0.005(stat)±0.009(syst)  GeV is also observed, in both the Υ(1S)γ and Υ(2S)γ decay modes. This structure is interpreted as the χ_{b}(3P) system.

OBJECTIVES: The aim of this study was to evaluate the predictive value of fragmented QRS (fQRS) among non-ST elevation acute coronary syndrome (ACS) patients. DESIGN: The fQRS on standard 12-lead ECGs in 179 patients (63% males, mean age 60.9 ± 12.3 years) were analyzed. Cardiac events and cardiac mortality were regarded as two outcomes to determine whether fQRS was a clinical prognostic factor; its prognostic value was then assessed adjusting for other covariates. RESULTS: Cardiac mortality (18 (17.0%) vs. 4 (5.5%)) and major cardiac event rate (46 (43.4%) vs. 22 (30.1%)) were higher in the fQRS group compared with the non-fQRS group during a mean follow-up of 12 months. A Kaplan-Meier survival analysis revealed significantly lower event-free survival for cardiac events (p = 0.030) and cardiac mortality (p = 0.020). Multivariate Cox regression analysis revealed that significant fQRS was an independent significant predictor for cardiac events and cardiac mortality. CONCLUSION: These results indicate that the occurrence of fQRS in the ECG is a powerful predictor of decreased survival in NSTEMI. The prognostic importance of fQRS was incremental to clinical and conventional factors.

Prior reports suggest that dreaming during anaesthesia is dependent on recovery time. Dreaming during sedation may impact patient satisfaction. The current study explores the incidence and content of dreaming during short-term sedation with sevoflurane or propofol and investigates whether dreaming is affected by recovery time. A total of 200 women undergoing first trimester abortion (American Society of Anesthesiologists physical status I) participated in the study. Patients were randomly assigned to receive either sevoflurane or propofol for short-term sedation. Patients were interviewed upon emergence with the modified Brice questionnaire. The results showed the incidence of dreaming was significantly different between anaesthesia groups with 60%(60/100) of the sevoflurane group and 33%(33/100) of the propofol group (P=0.000). However, recovery time did not significantly differ between groups. In the sevoflurane group, a greater number of dreamers could not recall what they had dreamed about (P=0.02) and more patients reported dreams that had no sound (P=0.03) or movement (P=0.001) compared with dreamers in the propofol group. Most participants reported dreams with positive emotional content and this did not significantly differ between groups. Anaesthesia administered had no effect on patient satisfaction. The results suggest that the incidence of dreaming was not affected by recovery time. Patient satisfaction was not influenced by choice of sedative and/or by the occurrence of dreaming during sevoflurane or propofol short-term sedation.

The purpose of this systematic review was to quantify the effects of psychological interventions on psychological health, physical health and disease activity in patients with systemic lupus erythematosus (SLE). Studies were identified through a systematic search of six electronic databases and were included if they used a randomized controlled trial designed to explore the effects of psychological interventions in patients with SLE. Two authors independently assessed the methodological quality of included studies using a quality-scoring instrument developed by Jadad et al. and extracted relevant information according to a pre-designed extraction form. Data was analysed using the Cochrane Collaboration's Revman5.1. Finally, six studies involving 537 patients were included. Meta-analysis showed that psychological interventions could reduce the levels of anxiety (standard mean difference (SMD)-0.95, 95% confidence interval (CI)-1.57,-0.34, p-value 0.00), depression (SMD -1.14, 95% CI -1.84,-0.44, p-value 0.00), stress (SMD -0.63, 95% CI -1.02,-0.23, p-value 0.00), and disease activity (SMD -0.34, 95% CI -0.57,-0.11, p-value 0.00). Although the effects on mental health, fatigue and physical function were in the expected direction, they were not statistically significant (p > 0.05). The present data indicate that psychological interventions are promising treatments for patients with SLE. The findings were based on only six randomized controlled trials (RCTs), some of which were relatively small, so more methodologically rigorous large-scale randomized controlled trials are required to confirm these preliminary estimates of effectiveness.

The large chromosomal deletions frequently observed in cancer genomes are often thought to arise as a "two-hit" mechanism in the process of tumor-suppressor gene (TSG) inactivation. Using a murine model system of hepatocellular carcinoma (HCC) and in vivo RNAi, we test an alternative hypothesis, that such deletions can arise from selective pressure to attenuate the activity of multiple genes. By targeting the mouse orthologs of genes frequently deleted on human 8p22 and adjacent regions, which are lost in approximately half of several other major epithelial cancers, we provide evidence suggesting that multiple genes on chromosome 8p can cooperatively inhibit tumorigenesis in mice, and that their cosuppression can synergistically promote tumor growth. In addition, in human HCC patients, the combined down-regulation of functionally validated 8p TSGs is associated with poor survival, in contrast to the down-regulation of any individual gene. Our data imply that large cancer-associated deletions can produce phenotypes distinct from those arising through loss of a single TSG, and as such should be considered and studied as distinct mutational events.

A dynamic blue-detuned optical dipole trap with stable (87)Rb atoms produces a differential ac Stark shift of 18 Hz in the ground state hyperfine transition, and it preserves the ground state hyperfine superpositions for a long coherence time of 180 ms. The trapped atoms undergoing microwave Rabi oscillations are sensitive to a small signal, artificially generated with a second microwave source, phase locked to the first allowing a simple and effective method for determining signal-to-noise ratio limits through interference techniques. This provides an excellent means of calibrating sensitivity in experiments such as our ongoing Fr parity non-conservation measurement.