Neuroprotective effect of Azadirachta indica standardized extract in partial sciatic nerve injury in rats

Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days. Various behavioral parameters, biochemical, molecular and histological parameters were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia, hy- peralgesia, motor coordination and motor nerve conduction velocity (MNCV) whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p < 0.05) these behavioral changes. Enhanced activity of oxidative- nitrosative stress, inflammatory mediators (TNF-α, IL-1β, and NF-κB) as well as mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p < 0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural apoptosis and reactive oxygen species levels. PSNL induced histological aberrations were also decreased by AI treatment. Azadirachta indica exerts its neuro- protection against PSNL induced neuropathic pain via inhibition of oxidative-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to improve MNCV (graphical abstract, Figure 1)

Evolution of orbital phases with particle size in nanoscale stoichiometric LaMnO3

The thermodynamically stable long-range orbital order in bulk LaMnO3 becomes metastable at nanoscale around a critical particle size d_C~20 nm. The orbital order-disorder transition switches from reversible to irreversible at d_C while the resistance in the orbital ordered state decays by 2-4% over a time scale of ~3000s. At well below d_C, of course, a stable orbital disordered phase emerges. The orthorhombic distortion of the underlying crystallographic structure (space group Pbnm) decreases systematically with the decrease in particle size and at far below d_C (e.g., at ~10 nm), the structure becomes cubic (space group Pm-3m). Using the crystallographic and electrical resistance data, a phase diagram has been constructed showing the evolution of different orbital phases as a function of particle size across ~10 nm to bulk for stoichiometric LaMnO3.Comment: revised following referees' comments, accepted for publicaton in J. Appl. Phy

Search for large extra dimensions in the production of jets and missing transverse energy in p(p)over-bar collisions at root s=1.96 TeV

We present the results of a search for new physics in the jets plus missing transverse energy data sample collected from 368 pb(-1) of p (p) over bar collisions at root s = 1.96 TeV recorded by the Collider Detector at Fermilab. We compare the number of events observed in the data with a data-based estimate of the standard model backgrounds contributing to this signature. We observe no significant excess of events, and we interpret this null result in terms of lower limits on the fundamental Planck scale for a large extra dimensions scenario

Measurement of the W+W- production cross section in p(p)over-bar collisions at root s=1.96 TeV using dilepton events

We present a measurement of the W+W- production cross section using 184 pb(-1) of p (p) over bar collisions at a center-of-mass energy of 1.96 TeV collected with the Collider Detector at Fermilab. Using the dilepton decay channel W+W-&RARR; l(+)ν l(-)(ν) over bar, where the charged leptons can be either electrons or muons, we find 17 candidate events compared to an expected background of 5.0(-0.8)(+2.2) events. The resulting W+W- production cross-section measurement of σ(p (p) over bar &RARR; W+W-)=14.6(-5.1)(+5.8)(stat)(-3.0)(+1.8)(syst)&PLUSMN; 0.9(lum) pb agrees well with the standard model expectation

Inferring causal molecular networks: empirical assessment through a community-based effort

Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks

Inferring causal molecular networks: empirical assessment through a community-based effort

It remains unclear whether causal, rather than merely correlational, relationships in molecular networks can be inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge, which focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective, and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess inferred molecular networks in a causal sense

Evaluation of health-related quality of life in hemolytic uraemic syndrome patients treated with eculizumab: a systematic evaluation on basis of EMPRO

<p><b>Background:</b> Hemolytic uraemic syndrome (HUS) is progressive renal failure disease and determination of their quality of life (QoL) on the basis of patient-reported outcomes (PROs) are becoming increasingly important in the economic evaluations for its treatment with eculizumab (ECU).</p> <p><b>Aim:</b> To perform the systematic evaluation of QoL in HUS patients treated with ECU on the basis of Evaluating Measures of Patient Reported Outcomes (EMPRO) tool.</p> <p><b>Materials and methods:</b> A systematic review was conducted in PubMed, EMBASE, the Cochrane Library, CINAHL and Google Scholar till September 2016 by two independent researchers. Each identified instrument was evaluated for its quality of performance by using the EMPRO tool for its overall score and seven attribute specific scores (range 0–100, worst to best).</p> <p><b>Results:</b> Five different PROs instruments were identified from 10 articles (<i>n</i> = 112) which showed eculizumab significantly improves health-related quality of life (HRQOL) in atypical HUS (aHUS) patients. Amongst five instruments viz. EuroQol five dimensions questionnaire (EQ-5 D), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Headache Impact Test-6 (HIT-6), 36-Item Short Form Health Survey (SF-36) and Visual Analogue Scale (VAS), the overall EMPRO score was higher for VAS (73.83) and EQ-5 D (73.81). Whereas, FACIT-F and HIT- 6 were just able to meet the minimal threshold of EMPRO scoring (50.24 and 59.09, respectively).</p> <p><b>Conclusions:</b> Evidence from present investigation support that eculizumab significantly improves HRQoL in patients with aHUS furthermore, EQ-5 D and VAS instrument should be recommended for assessing HRQoL in them. However, selection of PRO instrument for determination of QoL in HUS entirely depend upon the study requirements.</p

Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats

Background: Delayed wound healing is a diverse, multifactorial, complex and inter-related complication of diabetes resulting in significant clinical morbidity. Hesperidin possesses potent antidiabetic and wound healing activity. Aim: To evaluate the potential of hesperidin against experimentally induced diabetes foot ulcers. Methods: Diabetes was induced experimentally by streptozotocin (STZ, 55 mg/kg, i.p.) in Sprague Dawley rats (180-220 g) and wounds were created on the dorsal surface of the hind paw of rats. Hesperidin (25, 50 and 100 mg/kg, p.o.) was administered for 21 days after wound stabilization. Various biochemical, molecular and histopathological parameters were evaluated in wound tissue. Results: STZ-induced decrease in body weight and increase in blood glucose, food, and water intake was significantly (p < 0.05) inhibited by hesperidin (50 and 100 mg/kg) treatment. It showed a significant increase (p < 0.05) in percent wound closure and serum insulin level. The STZ-induced decrease in SOD and GSH level, as well as elevated MDA and NO levels, were significantly (p < 0.05) attenuated by hesperidin (50 and 100 mg/kg) treatment. Intraperitoneal administration of STZ caused significant down-regulation in VEGF-c, Ang-1, Tie-2, TGF-β and Smad 2/3 mRNA expression in wound tissues whereas hesperidin (50 and 100 mg/kg) treatment showed significant up-regulation in these mRNA expressions. STZ-induced alteration in would architecture was also attenuated by hesperidin (50 and 100 mg/kg) treatment. Conclusion: Together, treatment with hesperidin accelerate angiogenesis and vasculogenesis via up-regulation of VEGF-c, Ang-1/Tie-2, TGF-β and Smad-2/3 mRNA expression to enhance wound healing in chronic diabetic foot ulcers

Assessment of Salivary Cortisol and Dehydroepiandrosterone as Oral Biomarkers to Assess Stress in Patients with Recurrent Aphthous Stomatitis

Background: Recurrent aphthous stomatitis is a chronic inflammatory disease characterized by recurrent bouts of one or several shallow, rounded or ovoid, painful ulcers of oral mucosa that recur at intervals of a few days or up to 2–3 months and is of unknown etiology. The present study evaluated salivary cortisol and dehydroepiandrosterone as oral biomarkers to assess stress in patients with recurrent aphthous stomatitis (RAS). Materials &amp; Methods: 84 patients of recurrent aphthous stomatitis (RAS) were randomly divided into 2 groups of 41 each. Group I were RAS patients and group II were healthy control subjects. In all salivary cortisol and DHEA levels were measured. Results: DHEA levels 48–61 pg/ml was seen in 44% in group I and 10% in group II, &lt;48 pg/ml in 24% in group I and 86% in group II, &gt;61 pg/ml was seen in 32% in group I and 4% in group II. Salivary cortisol level &gt;3 ng/ml was seen in 83% in group I and 28% in group II and between 1.2–3 ng/mL in 15% in group I and 74% in group II. Conclusion: RAS patients exhibited higher salivary cortisol and DHEA levels as compared to the healthy controls