Miracle-dz/UniFAR-FTUs huggingface dataset:
FK506 neuroprotection after cavernous nerve injury is mediated by thioredoxin and glutathione redox systems.

INTRODUCTION Immunophilin ligands such as FK506 (FK) preserve erectile function (EF) following cavernous nerve injury (CNI), although the precise mechanisms are unclear. We examined whether the thioredoxin (Trx) and glutathione (GSH) redox systems mediate this effect after CNI. AIM To investigate the roles of Trx reductase 2 (TrxR2) and S-Nitrosoglutathione reductase (GSNOR) as antioxidative/nitrosative and antiapoptotic mediators of the neuroprotective effect of FK in the penis after CNI. METHODS Adult male rats, wild-type (WT) mice, and GSNOR deficient (GSNOR -/-) mice were divided into four groups: sham surgery (CN [cavernous nerves] exposure only) + vehicle; sham surgery + FK (5 mg/kg/day/rat or 2 mg/kg/day/mouse, for 2 days, subcutaneous); CNI + vehicle; and CNI + FK. At day 4 after injury, electrically stimulated changes in intracavernosal pressure (ICP) were measured. Penises were collected for Western blot analysis of TrxR2, GSNOR, and Bcl-2, and for immunolocalization of TrxR2 and GSNOR. MAIN OUTCOME MEASURES EF assessment represented by maximal ICP and total ICP in response to electrical stimulation. Evaluation of protein expression levels and distribution patterns of antioxidative/nitrosative and antiapoptotic factors in penile tissue. RESULTS EF decreased after CNI compared with sham surgery values in both rats (P < 0.01) and WT and GSNOR -/- mice (P < 0.05). FK treatment preserved EF after CNI compared with vehicle treatment in rats (P < 0.01) and WT mice (P < 0.05) but not in GSNOR -/- mice. In rats, GSNOR (P < 0.01) and Bcl-2 (P < 0.05) expressions were significantly decreased after CNI. FK treatment in CN-injured rats restored expression of GSNOR and upregulated TrxR2 (P < 0.001) and Bcl-2 (P < 0.001) expressions compared with vehicle treatment. Localizations of proteins in the penis were observed for TrxR2 (endothelium, smooth muscle) and for GSNOR (nerves, endothelium, smooth muscle). CONCLUSIONS The neuroprotective effect of FK in preserving EF after CNI involves antioxidative/nitrosative and antiapoptotic mechanisms mediated, to some extent, by Trx and GSH systems.
Biphasic calcium response of platelet‐derived growth factor stimulated glioblastoma cells is a function of cell confluence

Previous reports have linked the spiking or two‐phased character of calcium transients evoked by platelet‐derived growth factor (PDGF) to the position of cells in the cell cycle without regard to cell–cell contact and communication. Because cell confluence can regulate growth factor receptor expression and dephosphorylation, we investigated the effect of cell culture confluence and cell cycle on calcium responses of PDGF‐BB–stimulated A172 glioblastoma cells.
Test-retest reliability of computerised hand dynamometry in adults with acquired brain injury.

BACKGROUND/AIM The ability to objectively and reliably measure hand performance over time is critical to monitor patient performance and evaluate treatment efficacy. Current spasticity measures are subjective in nature and fail to capture the complexity of the multi-faceted upper motor neuron syndrome. This study examined the test-retest reliability of dynamic computerised hand dynamometry for simultaneously measuring multiple aspects of positive and negative features of the upper motor neuron syndrome during an active grasp and release task. METHODS Community-living adults with upper motor neuron syndrome following acquired brain injury attending metropolitan spasticity clinics for management of upper limb spasticity (N = 36; mean age 50 years ±15) and control participants (N = 27, mean age 40 years ±12) completed a computerised hand dynamometry protocol across two testing occasions 5 weeks apart. Objective measurement of Isometric Force, Cycle Duration and Isometric Grip Work, Force Velocity, was completed during a repeated grasp and release test protocol with a computerised hand dynamometer to evaluate the reliability and reproducibility of hand performance. RESULTS Kendall Coefficient of Concordance W scores ranged from W = 0.69-0.98 for motor elements of grasp and release, including Isometric Force, Cycle Duration, Isometric Grip Work and Force Velocity. CONCLUSIONS The investigated dynamic computerised hand dynamometry protocol showed fair/good to excellent levels of test-retest reliability in control participants and in subjects with upper motor neuron syndrome following acquired brain injury.
Osteochondral Autograft Transplantation for Osteochondritis Dissecans of the Elbow in Juvenile Baseball Players

Background Osteochondral autografts have recently become popular to treat articular cartilage defects, and they are used for unstable osteochondritis dissecans lesions as a means of biological fixation. Purpose To evaluate the clinical results of osteochondral autograft transfer for osteochondritis dissecans of the elbow. Study Design Case series; Level of evidence, 4. Methods Osteochondral autograft transfer was performed on 18 baseball players (mean age, 13.6 years) with osteochondritis dissecans of the elbow. These included 9 lesions that were grade 3 (separated but in situ) and 9 lesions that were grade 4 (displaced fragment with osteochondral defect) based on magnetic resonance imaging. All patients were evaluated with a scoring system, radiographs, and magnetic resonance imaging, with the mean follow-up at 3.5 years. Results In patients with grade 3 lesions, the subjective score was increased, but the objective score did not change. Six of 9 patients returned to their previous sports performance levels. One quit baseball because of academic reasons, 1 changed his position, and 1 changed to softball. In patients with grade 4 lesions, both subjective and objective scores were increased significantly. All but 1 patient returned to their previous sports performance levels. In the 3 grade 4 lesions with a wide osteochondral defect, the irregularity of the articular surface remained on magnetic resonance imaging. Conclusion Osteochondral autograft transplantation is a useful treatment for reattachment of the lesion as well as osteochondral resurfacing of elbow osteochondritis dissecans.
Employees' Social Networking Site Use Impact on Job Performance: Evidence from Pakistan

This paper reinvestigates the impact of social networking site use by employees on job performance by conducting a methodological replication of Moqbel, Nevo, and Kock (2013) using samples (N=139) from Pakistan. In both studies, social networking site use has significant effects on organizational commitment and job satisfaction, and job satisfaction also has a significant impact on job performance and organizational commitment. In comparison with the U.S., we find that social networking site use in Pakistan has no significant impact on job performance through the mediating effect of job satisfaction, yet has a significant effect on organizational commitment and job satisfaction. In conclusion, although social networking site use does not have an impact on job performance per se, it does have significant effects on other work-related outcomes—job satisfaction and organizational commitment. Future studies are encouraged to methodologically replicate this study in several different countries to examine whether results hold and conceptually replicate this study by measuring presenteeism and work-life balance as mediators to see if the theorizing of the original study holds.
Herpes Simplex Virus Type 1 DNA Is Immunostimulatory In Vitro and In Vivo

ABSTRACT Recently, prokaryotic DNAs containing unmethylated CpG motifs have been shown to be intrinsically immunostimulatory both in vitro and in vivo, tending to promote Th1-like responses. In contrast, CpG dinucleotides in mammalian DNAs are extensively methylated on cytosines and hence immunologically inert. Since the herpes simplex virus (HSV) genome is unmethylated and G+C rich, we predicted that CpG motifs would be highly prevalent in the HSV genome; hence, we examined the immunostimulatory potential of purified HSV DNA in vitro and in vivo. Mouse splenocyte cultures treated with HSV DNA or HSV-derived oligodeoxyribonucleotides (ODNs) showed strong proliferative responses and production of inflammatory cytokines (gamma interferon [IFN-γ], tumor necrosis factor [TNF], and interleukin-6 [IL-6]) in vitro, whereas splenocytes treated with mammalian CV-1 DNA or non-CpG ODN did not. After immunization with ovalbumin (OVA), only splenocytes from mice immunized with HSV DNA or HSV-ODN as the adjuvants proliferated strongly and produced typical Th1 responses, including CD8+ cytotoxic T-lymphocyte responses, upon restimulation with OVA. Furthermore, HSV-ODN synergized with IFN-γ to induce nitric oxide (NO), IL-6, and TNF production from macrophages. These results demonstrate that HSV DNA and HSV-ODN are immunostimulatory, driving potent Th1 responses both in vitro and in vivo. Considering that HSV DNA has been found to persist in nonneuronal cells, these results fuel speculation that HSV DNA might play a role in pathogenesis, in particular, in diseases like herpes stromal keratitis (HSK) that involve chronic inflammatory responses in the absence of virus or viral antigens.
Effects of the Lack of Phosphatidylglycerol on the Donor Side of Photosystem II1[OA]

Our previous studies with the pgsA mutant of the cyanobacterium Synechocystis sp. PCC6803 (hereafter termed pgsA mutant), which is defective for the biosynthesis of phosphatidylglycerol (PG), revealed an important role for PG in the electron acceptor side of photosystem II (PSII), especially in the electron transport between plastoquinones QA and QB. This study now shows that PG also plays an important role in the electron donor side of PSII, namely, the oxygen-evolving system. Analyses of purified PSII complexes indicated that PSII from PG-depleted pgsA mutant cells sustained only approximately 50% of the oxygen-evolving activity compared to wild-type cells. Dissociation of the extrinsic proteins PsbO, PsbV, and PsbU, which are required for stabilization of the manganese (Mn) cluster, followed by the release of a Mn atom, was observed in PSII of the PG-depleted mutant cells. The released PsbO rebound to PSII when PG was added back to the PG-depleted mutant cells, even when de novo protein synthesis was inhibited. Changes in photosynthetic activity of the PG-depleted pgsA mutant cells induced by heat treatment or dark incubation resembled those of ΔpsbO, ΔpsbV, and ΔpsbU mutant cells. These results suggest that PG plays an important role in binding extrinsic proteins required for sustaining a functional Mn cluster on the donor side of PSII.
Death of dopaminergic neurones in the rat substantia nigra can be induced by damage to globus pallidus

Parkinson's disease is a debilitating disorder that results from the death of dopaminergic neurones in the substantia nigra. Subthalamic nucleus neurones use glutamate as their neurotransmitter and send excitatory projections to the substantia nigra. Changes in both the mean firing rate and firing pattern of neurones of the subthalamic nucleus have been found in patients with this disease. This has led to the suggestion that hyperactivity of the subthalamic nucleus may be involved in the pathology of the dopaminergic neurones. Subthalamic nucleus lesions or treatment with glutamatergic antagonists can be neuroprotective in animal models of Parkinson's disease but until now there has been no direct evidence that hyperactivity of subthalamic nucleus neurones can lead to downstream cell death. Here we show that lesions of the rat globus pallidus (a treatment that has been shown to increase subthalamic nucleus neuronal activity) result in a significant reduction of the number of dopaminergic neurones in the substantia nigra.
Development of a bioactive porous collagen/β-tricalcium phosphate bone graft assisting rapid vascularization for bone tissue engineering applications.

We developed collagen (COL) and collagen/beta tricalcium phosphate (COL/β-TCP) scaffolds with a β-TCP/collagen weight ratio of 4 by freeze-drying. Mouse bone marrow-derived mesenchymal stem cells (BMMSCs) were cultured on these scaffolds for 14 days. Samples were characterized by physicochemical analyses and their biological properties such as cell viability and alkaline phosphatase (ALP) activity was, also, examined. Additionally, the vascularization potential of the prepared scaffolds was tested subcutaneously in Wistar rats. We observed a microporous structure with large porosity (∼95-98%) and appropriate pore size (120-200 µm). The COL/β-TCP scaffolds had a much higher compressive modulus (970 ± 1.20 KPa) than pure COL (0.8 ± 1.82 KPa). In vitro model of apatite formation was established by immersing the composite scaffold in simulated body fluid for 7 days. An ALP assay revealed that porous COL/β-TCP can effectively activate the differentiation of BMMSCs into osteoblasts. The composite scaffolds also promoted vascularization with good integration with the surrounding tissue. Thus, introduction of β-TCP powder into the porous collagen matrix effectively improved the mechanical and biological properties of the collagen scaffolds, making them potential bone substitutes for enhanced bone regeneration in orthopedic and dental applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 73-85, 2018.
Additive Value of Heart Rate Variability in Predicting Obstructive Coronary Artery Disease Beyond Framingham Risk.

BACKGROUND Heart rate variability (HRV) is usually reduced in patients with CAD. We therefore investigated whether reduced HRV is predictive of angiographic CAD beyond Framingham risk in patients with stable angina. METHODSANDRESULTS A total of 514 patients (age, 66.1 ± 14.3 years, 358 men) were enrolled. Holter ECG was performed before catheterization, and 24-h HRV was analyzed in both the frequency domain (VLF, LF, HF and total power) and the time domain (SDNN, SDANN, RMSSD and pNN20). Angiographic CAD was defined as ≥ 50% diameter reduction of 1 or more coronary arteries. On coronary angiography 203 patients (39.6%) had angiographic CAD. Patients with CAD had significantly higher Framingham risk and lower HRV according to both frequency and time domain parameters. After controlling for age, gender, heart rate, SBP, renal function, lipids and Framingham risk, reduced HRV indices remained predictors of CAD (OR, 95% CI for LF, HF, SDNN, RMSSD and pNN20: 0.81, 0.66-0.99; 0.77, 0.63-0.94; 0.75, 0.59-0.96; 0.72, 0.58-0.88; and 0.76, 0.62-0.94, respectively). On subgroup analysis, HRV parameters appeared to be predictive of CAD only in subjects with high Framingham risk or diabetes. CONCLUSIONS Reduced HRV is predictive of CAD in patients with stable angina, independent of traditional risk factors and Framingham risk. The predictive value of HRV may be relevant only in subjects with high Framingham risk or diabetes.
Young women's risk of sexual aggression in bars: the roles of intoxication and peer social status.

INTRODUCTION AND AIMS Previous research suggests a link between women's drinking and sexual victimisation; however, little is known about other factors that influence risk and how risks are linked to drinking-in-the-event. We examined how amount of alcohol consumed and peer group factors were associated with whether young women were targeted for sexual aggression on a night out at a bar. DESIGN AND METHODS One hundred and fourteen women recruited in small groups in the bar district reported how many drinks they had consumed and were breath-tested at recruitment and on their way home. At recruitment, they also ranked other members of their group in terms of status (e.g. popularity, group influence). In the exit survey, they reported any sexual aggression they experienced that night (i.e. persistence after refusal and unwanted sexual touching). RESULTS Over a quarter (28.9%) of women reported persistence only, 5.3% unwanted touching only and 18.7% both. Sexual aggression was associated with consuming more alcohol on the survey night and whether other group members experienced sexual aggression that night. The relationship with amount consumed was stronger for touching than for persistence. Having a lower status position in the group was associated with increased risk of sexual aggression among women who had consumed five or more drinks. DISCUSSION AND CONCLUSIONS Prevention should address social norms and other factors that encourage men to target specific women for sexual aggression, including perceptions by staff and patrons that intoxicated women are 'easy' or more blameworthy targets and the possible role of women's social status in their peer groups.
Sex Differences in Alcohol Use Disorder.

BACKGROUND Alcohol use disorder (AUD) is a common and disabling mental disorder associated with a significant burden of medical consequences and high socioeconomic costs. Although a growing number of studies support the existence of sex differences in several aspects of alcohol consumption and AUD, the majority of investigations have been conducted in men. OBJECTIVE This article was aimed at reviewing sex differences in AUD, focusing on epidemiology, neurobiology, pharmacokinetics, susceptibility to medical consequences, and treatment. RESULTS Although AUD is more prevalent in men, the number of women with AUD is rapidly increasing, especially in adolescents. Women show a higher vulnerability to medical consequences induced by alcohol consumption, including alcohol-related liver disease, cardiomyopathy, and breast cancer. This observation is only partly explained by the sex differences observed in the pharmacokinetics of alcohol. Women also show an accelerated progression from the first use of alcohol to the onset of AUD and appear to be at higher risk of alcohol- medication interactions. Although AUD women are less likely to seek treatment than men, they achieve better results through dedicated programs taking into account the special needs of female patients. However, findings on the efficacy and safety of medications used to treat AUD mostly come from studies in which women were largely underrepresented. CONCLUSION The sex differences observed suggest the urgent need to conduct studies recruiting adequate numbers of female subjects, to increase knowledge of sex differences in AUD, and to develop personalized and evidence-based approaches of prevention and treatment of AUD in women.
Effect of low-molecular-weight heparin on survival in patients with advanced pancreatic adenocarcinoma

Summary This retrospective analysis aimed to identify whether low-molecular- weight heparins (LMWH) might improve survival in patients receiving chemotherapeutic treatment for advanced pancreatic adenocarcinoma.Two hundred forty-three patients who had received chemotherapy for advanced pancreatic adenocarcinoma were identified from a prospectively maintained database. Of these, 30 patients had to be excluded from analysis due to insufficient documentation. Of the remaining 213 patients 94 patients had been treated with LMWH, whereas 119 patients served as controls. Outcome was assessed in relation to overall survival, which was calculated from the date of initiation of chemotherapy to the date of death.There was no significant difference (hazard ratio, 0.8; 95% confidence interval (CI), 0.6 to 1.1; P=0,2) between the two groups in terms of overall survival. The median survival was 7.1 months (95% CI,5.8–8.4 months) in the LMWH group and 5.9 months (95% CI, 5.1–6.7 months) in the non-LMWH group. A positive effect of LMWH was seen in patients with metastatic disease (hazard ratio for LMWH vs. non-LMWH, 0,6; 95% CI, 0,4 to 0,8; P=0,006) in contrast to those without metastatic disease (hazard ratio for LMWH vs. non-LMWH, 1; 95% CI, 0.6 to 1.7; P=0,96). The median survival of patients with metastatic disease was 6,6 months (95% CI, 5–8,2 months) and 3.8 months (95% CI, 2.5–5.1 months) for the LMWH group and the non-LMWH group, respectively. In conclusion, we found for metastatic pancreatic adenocarcinoma a survival advantage for patients receiving LMWH. Nevertheless, our observations need confirmation by prospective randomized studies.
A low complexity scheduling scheme based on multi-user beamforming in TD-LTE downlink

Multi-user multi-input and multi-output based on block diagonalization algorithm can eliminate the multi-user interference, but in fact the existence of the non-ideal factors lead to the interference can not be cancelled completely. In this paper we study the performance of the 3GPP long term evolution system based on BD algorithm and propose a low complexity multi-user scheduling scheme to reduce the mismatch between the CQI and the PostSINR. To get the tradeoff between the cell average capacity and the cell edge user capacity, proportional fairness scheduling is applied. Finally, simulation results with 3GPP LTE are presented using system level simulator.
Transplanted corneal stromal cells in vitreous reproduce extracellular matrix of healing corneal stroma.

PURPOSE To characterize the extracellular matrix (ECM) formed by corneal stromal cells after injection into the vitreous. This will provide a basis for future studies on the function of corneal ECM macromolecules. METHODS Cell line from rabbit dermal fibroblasts (RAB9) and primary cultures of rabbit corneal stroma fibroblasts (NRCF) were grown to confluence. For each cell type, approximately 1 x 10(6) cells suspended in basal medium were injected into the vitreous of normal rabbits and observed periodically with a slit lamp. After 1,2, and 4 weeks, eyes were processed for transmission electron microscopy (TEM), immunohistochemistry, immunocytochemistry, and in situ hybridization. RESULTS All cells showed gradual growth within the vitreous along the needle track. Occurrence of retinal detachment and inflammation was variable. Transmission electron microscopy of NRCF confirmed the deposition of ECM reminiscent of the organization of normal fetal corneal stroma. Similar matrices were produced by RAB9. NRCF deposited collagen fibrils similar in diameter to those seen in normal developing and healing corneal stroma. RAB9 produced collagen fibrils with larger diameters. NRCF-transplanted cells synthesized proteoglycans and collagen immunologically identical to decorin proteins and type VI collagen, indicating that the expression of specific ECM is maintained after transplantation. In addition, in situ hybridization showed that type XII collagen mRNA is synthesized by transplanted NRCF similar to healing corneas. CONCLUSIONS Corneal stromal cells transplanted into vitreous produce a matrix morphologically and biochemically similar to that in healing corneal stroma.
A single olfactory receptor specifically binds a set of odorant molecules

The sense of smell is mediated by the initiation of action potential in olfactory sensory neurons during odor stimulation. However, little is known about odorant‐olfactory receptor (OR) recognition mechanisms. In the present work, we identified the structural motifs of odorant molecules required to activate mouse OR912‐93 by detection of the odorant response using calcium measurement in cells transfected with OR and Gαq and Gα15 proteins. The use of sets of odorants led to the identification of ketones with an aliphatic carbon chain length ≥ four carbon atoms and a carbonyl group preferentially located in position C2 or C3. The threshold of detection of these odorants is as low as 10−6−10−8m. No other odorant ligand, out of 70 representatives of the odorant world, was active. The human ortholog of OR912‐93 is not functional, suggesting that apart from a stop‐mutation located at the 5′‐end that was corrected in the construct, it incurred other deleterious mutations during evolution.