Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of tiagabine on sleep in elderly subjects with primary insomnia: a randomized, double-blind, placebo-controlled study.

SUBJECT OBJECTIVE This study further evaluated the effects of tiagabine on sleep in elderly subjects with primary insomnia. METHODS Elderly subjects (aged 65-85 years) meeting DSM-IV-TR criteria for primary insomnia were randomly assigned to receive tiagabine 2, 4, 6, or 8 mg or placebo on 2 consecutive nights. Efficacy was assessed using standard polysomnography and a postsleep questionnaire. Additional assessments included the Assessment of Daily Functioning, Digit Symbol Substitution Test (for residual effects), and visual analog scale (for sleepiness/alertness). RESULTS A total of 207 subjects were randomly assigned to study medication (tiagabine: 2 mg, n = 43; 4 mg, n = 38; 6 mg, n = 45; 8 mg, n = 43; placebo, n = 38). Tiagabine did not significantly effect wake after sleep onset, latency to persistent sleep, or total sleep time compared with placebo (P > .05). Significant increases in Stage 3+4 sleep (i.e., slow-wave sleep) were found for tiagabine 4, 6, and 8 mg versus placebo, with a corresponding significant decrease in Stage 1 sleep (P < .05). At 6 and 8 mg, tiagabine also significantly reduced the number of awakenings and increased the ratio of Stage 3+4/(Stage 1 +wake after sleep onset). In general, there were no significant effects on subjects' ratings of sleep or daily functioning with tiagabine 2, 4, and 6 mg versus placebo. These 3 doses had tolerability profiles comparable with that of placebo and were not associated with significant residual effects or reduced alertness. The 8-mg dose, however, significantly decreased subjective total sleep time and refreshing quality of sleep, as well as daily functioning. This dose was associated with troublesome adverse events, significant residual effects, and reduced alertness. CONCLUSIONS In elderly subjects with primary insomnia, tiagabine did not have a significant effect on wake after sleep onset, latency to persistent sleep, total sleep time, or the subjective rating of sleep. Tiagabine 4, 6, and 8 mg significantly increased slow-wave sleep, with a corresponding significant decrease in Stage 1 sleep. Tiagabine was generally well tolerated, with doses of less than 6 mg having tolerability profiles generally similar to that of placebo. The 8-mg dose, however, was associated with troublesome adverse events, residual effects, and reduced alertness.
Low dose bolus aminocaproic acid: an alternative to platelet transfusion in thrombocytopenia?

To the Editor: Antifibrinolytic agents such as epsilon-aminocaproic acid (EACA) have been used in a few studies to control bleeding in thrombocytopenic states where the patients are refractory to usual platelet transfusions (1-4). In spite of encouraging results it has not been evaluated as primary therapy, possibly because availability of platelet support is not a problem in developed countries. However, in a developing country such as ours, considerations of cost and availability have always been a hindrance to optimal platelet transfusion in thrombocytopenic states. Although most of the studies used the usual antifibrinolytic dose (8-24 g/d) of EACA (1, 2,4), Bartholomew et al. showed equivalent efficacy with 6 gld of EACA (3). EACA is usually administered as an infusion (5). We have used smaller bolus doses of EACA as primary therapy in thrombocytopenic bleeding. Fifteen patients (age range 13-67 yr) with bleeding manifestations having severe thrombocytopenia (platelet count less than 2Ox1Oy/1) of varied aetiology, not having DIC or renal failure, received intravenous EACA as primary therapy. There were 4 patients each with acute lymphoblastic and non-lymphocytic leukaemias, 5 patients with autoimmune thrombocytopenic purpura and 2 patients with aplastic anaemia. Nine patients had bleeding from multiple sites. Five had gum bleeding, 4 patients had epistaxis, 3 had gastrointestinal bleeding, 2 had haematuria and 1 had menorrhagia as the predominant site of haemorrhage. The mean platelet count was 6.3k3. 3x109/1 (range 3-15x109/1). Ten patients had major haemorrhage (requiring inpatient monitoring, blood transfusions or occurring at critical sites such as the brain) and they received a loading dose of 5 g of EACA as infusion followed by slow bolus doses of 1 g every 6 h, increased to every 4 h in case of non-response over 24 h. Five other patients having non-major haemorrhage received a starting dose of 250 mg every 6 h. The maximum dose used in all the patients was 6 g/d. No response to this dose was considered as nonresponse and they were treated with platelet transtransfusion in
Laplacian dynamics on signed networks

In this paper, we examine the properties of the Laplacian matrix defined on signed networks, referred to as the signed Laplacian matrix, from a graph-theoretic perspective. The connection between the stability of the signed Laplacian with the cut set of the network is established. This is then followed by relating and the number of negative eigenvalues of the signed Laplacian to the number of negatively weighted edges in the network. In order to stabilize the signed Laplacian dynamics, a distributed diagonal compensation approach is proposed; we show that this compensation is closely related to the structural balance of the network. Furthermore, the influence of the external input exerted on the signed Laplacian dynamics is investigated.
Novel HLA-B27-restricted Epitopes from Chlamydia trachomatis Generated upon Endogenous Processing of Bacterial Proteins Suggest a Role of Molecular Mimicry in Reactive Arthritis*

Background: Reactive arthritis is an HLA-B27-associated disease triggered by Chlamydia trachomatis. Results: Three chlamydial peptides endogenously presented by HLA-B27 were identified. All were homologous to human-derived sequences, and one showed conformational similarity to a self-derived HLA-B27 ligand. Conclusion: Molecular mimicry between chlamydial and self-derived HLA-B27 ligands is not uncommon. Significance: Molecular mimicry may contribute to the pathology of reactive arthritis. Reactive arthritis (ReA) is an HLA-B27-associated spondyloarthropathy that is triggered by diverse bacteria, including Chlamydia trachomatis, a frequent intracellular parasite. HLA-B27-restricted T-cell responses are elicited against this bacterium in ReA patients, but their pathogenetic significance, autoimmune potential, and relevant epitopes are unknown. High resolution and sensitivity mass spectrometry was used to identify HLA-B27 ligands endogenously processed and presented by HLA-B27 from three chlamydial proteins for which T-cell epitopes were predicted. Fusion protein constructs of ClpC, Na+-translocating NADH-quinone reductase subunit A, and DNA primase were expressed in HLA-B27+ cells, and their HLA-B27-bound peptidomes were searched for endogenous bacterial ligands. A non-predicted peptide, distinct from the predicted T-cell epitope, was identified from ClpC. A peptide recognized by T-cells in vitro, NQRA(330–338), was detected from the reductase subunit. This is the second HLA-B27-restricted T-cell epitope from C. trachomatis with relevance in ReA demonstrated to be processed and presented in live cells. A novel peptide from the DNA primase, DNAP(211–223), was also found. This was a larger variant of a known epitope and was highly homologous to a self-derived natural ligand of HLA-B27. All three bacterial peptides showed high homology with human sequences containing the binding motif of HLA-B27. Molecular dynamics simulations further showed a striking conformational similarity between DNAP(211–223) and its homologous and much more flexible human-derived HLA-B27 ligand. The results suggest that molecular mimicry between HLA-B27-restricted bacterial and self-derived epitopes is frequent and may play a role in ReA.
Knockdown of ezrin via RNA interference suppresses Helicobacter pylori-enhanced invasion of gastric cancer cells

Background and Aim: H. pylori interacts with gastric epithelial cells, which may activate signaling pathways important for gastric cancer invasion. Ezrin, a membrane cytoskeletal crosslinker protein, is well documented to regulate cell adhesion and cell motility. The aim of the present study was to determine whether ezrin is involved in H. pylori-induced cancer cell motility and invasion. Methods: The VIL-2 of RNA interference plasmid vector and control plasmid vector were constructed. AGS (a human gastric adenocarcinoma cell line) cells were transfected by these plasmid vectors. The stable expression cell lines AGSezrin was obtained by G418 resistance screening. The express levels of ezrin protein and the cellular invasive potential of four groups, including the AGS control, AGSezrin control, AGS co-culture with H. pylori, AGSezrin co-culture with H. pylori were detected. Meanwhile, the morphology, cell migration and adhesion were determined respectively. Results: Co-culture with H. pylori stimulated AGS cell motility and invasion, up-regulated ezrin expression at the protein level and induced a Hummingbird phenotype. The silencing of ezrin expression suppressed the motility and invasion of gastric cancer cells and inversed the cell invasion phenotype and enhanced the ability for cell adhesion. Conclusion: Knockdown of ezrin by RNAi suppresses H. pylori-enhanced migration and invasion of gastric cancer cells. These findings indicate that ezrin may play a key role in the migration and invasion of gastric cancer cells, and thus may be a therapeutic target to prevent metastasis of gastric cancer promoted by H. pylori infection.
Differential Splicing of Antigen-Encoding RNA Reduces Endogenous Epitope Presentation That Regulates the Expansion and Cytotoxicity of T Cells1

The activation of CTLs is dependent on the recognition of MHC-bound peptide present on the surface of APCs. We give evidence in this study that differential splicing of Ag-encoding RNA can decrease the antigenic dose in APCs and regulate the recall of human memory CTLs. Differential splicing of RNA that encoded an immunodominant HLA-B8-restricted CTL epitope of EBV reduced the functional presentation of this epitope, and consequently the in vitro expansion and activity of CTLs, as measured by MHC/peptide-tetramer staining and cytotoxicity assays. The reduced activity of the stimulated CTLs was not only due to lower numbers of Ag-specific CTLs but, surprisingly, was also characterized by decreased cytotoxicity of the CTLs to target cells presenting limiting amounts of the peptide epitope. As indicated by TCR repertoire analysis, the reduction in CTL activity was not caused by stimulation of distinct populations of TCR clonotypes. This study demonstrates how a common eukaryotic posttranscriptional mechanism of gene regulation can modulate the endogenous presentation of Ag and ultimately contribute to the fine tuning of immunological memory cells, which are important in the fight against pathogens and tumors and in autoimmunity.
Effect of dietary iron on the course of Plasmodium berghei malaria in young rats.

Clinical and experimental evidence suggests that iron-deficient hosts are less susceptible to severe malaria and that iron supplementation aggravates infection. In the present study, 60 weanling Wistar rats were fed standard diets with different iron concentrations: 21 mg/kg (group 1), 45 mg/kg (group 2) and 113 mg/kg (group 3). Ferrous sulfate (FeSO4 x 7H2O) was added to the normal-iron and iron-supplemented diets (groups 2 and 3, respectively). Data are reported as mean +/- SEM. After 16 days of regimen, eight rats from each group were killed to measure serum iron concentration (SI) and transferrin saturation capacity (TSC). At this moment, rats from group 1 were underweight and their dietary intake was significantly lower than that of animals from the other groups. Severe iron deficiency (SI = 49.2 +/- 4.5 micrograms/100 ml and TSC = 8.3 +/- 0.7%) was observed in rats from group 1, while the animals from the other groups were iron-sufficient (group 2: SI = 186.5 +/- 28.5 micrograms/100 ml and TSC = 27.3 +/- 3.4%; group 3: SI = 137.3 +/- 18.2 micrograms/100 ml and TSC = 21.3 +/- 2.3%). Nine animals from each group were then infected with the malaria parasite Plasmodium berghei, whereas three animals from each group were used as noninfected controls. Parasitemias (% of infected red blood cells) peaked 7 days post-infection in animals from groups 2 and 3 (mean values of 2.4% and 1.7%, respectively), but in animals from group 1 parasitemias increased until the 9th day post-infection (mean at peak, 2.3%) and parasite clearance was significantly slower than in the other groups. (ABSTRACT TRUNCATED AT 250 WORDS)
Localism and police governance in England & Wales: Exploring continuity and change

This article develops further criminological understandings of ‘localism’ in police governance and contributes to broader theoretical discussions about ‘governance’ in contemporary policing, via a critical analysis of major recent law and policy reforms in England & Wales. Recent legislation has brought important changes to the balance of constitutional-legal powers and the institutional architecture of police governance. However, we argue that for several reasons it is problematic to interpret these developments in straightforward terms of greater ‘localization’. First, in so far as there has been a decentralization of control, this represents a growth of ‘regional’ rather than ‘local’ auspices of power. Second, there is widespread evidence of continuing interventionism by ‘the centre’, asserting strong influences on local policing via a range of national bodies. Third, important developments in the wider context of police policy-making – most importantly the conditions of austerity – have circumscribed the capacity of Commissioners to set their own policy agendas and resulted in a retrenchment of policing provision at the most ‘localized’ geographical units of neighbourhoods. Indeed, the combination of decentralizing formal responsibility for policing policy and restrictive central financial controls amounts in practice to a ‘devolution of blame’ by the centre for falling service standards. Finally, we argue that the growing complexity and fragmentation of police governance cannot be captured adequately by ‘vertical’ analysis of central–local relations. Although central influences remain predominant, policing policy networks have become more diverse, with important developments at ‘horizontal’ levels locally, regionally and nationally. Within this more fragmented governance framework, central influences continue to drive local policing, but primarily via a range of ‘arm’s length’ institutions and techniques.
Effects of isosorbide-5-mononitrate compared with propranolol on first bleeding and long-term survival in cirrhosis.

BACKGROUND & AIMS Isosorbide-5-mononitrate (Is-5-Mn) exerts beneficial hemodynamic effects in portal hypertension, yet the long-term clinical value is uncertain. The aim of this study was to determine the long-term effects of Is-5-Mn vs. propranolol (Pro) on first bleeding, complications, and death in cirrhosis. METHODS One hundred eighteen patients included in a previously published randomized trial comparing Is-5-Mn (20 mg three times daily) with Pro were followed up for up to 7 years (range, 2-91 months). Fifty-seven patients received Is-5-Mn and 61 received Pro. RESULTS Thirty episodes of first upper bleeding occurred; 16 were in the Is-5-Mn group. Actuarial probability of bleeding did not differ between the two groups. Endoscopic variceal red signs were the only independent predictors of early bleeding. Of the 52 patients who died, 28 were in the Is-5-Mn group. The likelihood of death was greater among patients assigned to Is-5-Mn than to Pro, but only in patients older than 50 years (72% vs. 48% at 6 years; P = 0.006). Child-Pugh score, bleeding, age, and assignment to Is-5-Mn were independent predictors of death. The likelihood of death without bleeding was also higher (P = 0.05) in the Is-5-Mn group. CONCLUSIONS Is-5-Mn is as effective as Pro in preventing early bleeding but is associated with higher long-term mortality.
Análisis de la eficacia de los saques de esquina en la copa del mundo de fútbol 2010

Las acciones a balon parado (ABP) en futbol son todas aquellas situaciones de juego que se inician con un saque desde parado despues de una interrupcion reglamentaria del mismo. En este trabajo se ha pretendido analizar la eficacia de una de estas acciones, el saque de esquina; identificar las variables mas relevantes para conducir al exito (el remate) a estas acciones y proponer un modelo de saque de esquina exitoso. Despues del registro de 554 saques de esquina ejecutados en el Mundial de Sudafrica 2010 y de realizar analisis a nivel univariado, bivariado y multivariado, los resultados indican una baja eficacia en el remate en este tipo de acciones, la identificacion de una serie de variables que presentan una relacion estadisticamente significativa y la propuesta de un modelo explicativo, que aunque presenta una capacidad explicativa limitada, ayuda a interpretar de forma practica la ejecucion de estas acciones.
Sickle cell disease: ratio of blood flow velocity of intracranial to extracranial cerebral arteries--initial experience.

PURPOSE To establish reference values of the ratios of flow velocity in the middle cerebral artery (V(MCA)) and the terminal portion of the internal carotid artery (V(tICA)) to flow velocity in the extracranial portion of internal carotid artery (V(ICA)) in children with sickle cell disease (SCD). MATERIALS AND METHODS Institutional ethics committee approval and parental informed consent were obtained for this prospective HIPAA-compliant study. Sixty-eight children (38 female; mean age, 7.7 years +/- 3.3; range, 2-14 years) with HbSS genotype, without neurologic deficits and no history of stroke, were enrolled. Final study population comprised 56 (mean age 8.0 +/- 3.3 years, 26 females) children who underwent magnetic resonance (MR) angiography, which excluded intracranial arterial narrowing, transcranial color-coded duplex ultrasonography (US), and carotid US to determine V(MCA)/V(ICA) and V(tICA)/V(ICA) ratios from angle-corrected and uncorrected velocities. Tolerance interval estimates were used to calculate reference ranges and linear regression was used to quantify associations of Doppler parameters with age adjusted for hemoglobin and hematocrit. RESULTS Reference ranges in centimeters per second for mean angle-corrected V(MCA) on the left and right sides were 62-198 and 69-153; those for V(tICA) were 30-196 and 36-175; and those for V(ICA) were 18-116 and 15-95, respectively. Reference ranges for mean angle-corrected V(MCA)/V(ICA) ratio on the left and right sides were 1.2-4.0 and 0.4-3.4 and those for V(tICA)/V(IC)(A) ratio were 0.5-2.9 and 0.5-2.7, respectively. V(MCA), V(tICA), and V(tICA)/V(ICA) ratio were not age dependent, contrary to V(ICA) and V(MCA)/V(ICA) ratio, after controlling for hematocrit and hemoglobin. CONCLUSION The study provides reference limits for V(MCA), V(tICA), V(ICA), and velocity ratios obtained from children with SCD.
Comparative quantitative expression of bcl‐2 by normal and leukaemic myeloid cells

Summary. Expression of the bcl‐2 oncoprotein by AML blasts has previously been demonstrated to be heterogenous with high levels of bcl‐2 expression being associated with a low complete remission rate and poor survival. We have quantified bcl‐2 expression in AML blasts in relation to expression of the CD34 antigen and in comparison to CD34‐positive cells from normal bone marrow. When expressed as molecules of equivalent soluble fluorochrome (MESF) per cell, AML blast cell bcl‐2 expression varied from 11.1 to 99.9 × lO3 (median 39.4 × 103, n=56) with 28.5% of patients expressing high MESF values (>50 × 103) and 16% of patients expressing low MESF values (<20 × 103), the remainder expressing intermediate values. There was no significant difference between intensity of bcl‐2 expression and FAB classification in the de novo AML cases, and there was no significant differences between de novo and secondary AML cases. Blasts from CD34+ AML patients expressed significantly higher levels of bcl‐2 (mean MESF 43.6 × 103, n =36) than CD34− AML patients (mean MESF 31.7 × 103, n=19).
Antimicrobial Activity of Black Pepper (Piper nigrum L.)

Black pepper (Piper nigrum L.) native of south India popularly known as" king of spices". Pepper is mostly used in the curry recipes as masalas and also as ingredient in the prescriptions of folk medicine, Ayurveda and traditional medicinal systems. The spicy tang of pepper is due to the presence of piperamides which are the pungent bioactive alkaloids accumulate in the skin and seeds of the fruit. Among them piperine is the major chemical constituent responsible for the bitter taste of the black pepper. In the present study piperine was evaluated for its antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, Alternaria alternata, Aspergillus niger, Aspergillus flavus and Fusarium oxysporum. The antibacterial activity was measured by agar well diffusion method and antifungal activity by poisoned food technique. Piperine showed antimicrobial activity against all tested bacteria with zone of inhibition ranged from 8-18mm. maximum zone of inhibition was against Gram positive bacteria Staphylococcus aureus (18mm) and minimum against Gram negative bacteria Escherichia coli (8mm). Piperine showed maximum antifungal activity towards Fusarium oxysporum (14mm) and very least effect against Aspergillus niger (38mm). The results showed significant activity of piperine and suggesting its use as natural antimicrobial agent.
MRI findings of Aspergillus spondylitis.

OBJECTIVE The aim of this retrospective study is to report the MRI findings of biopsyproven Aspergillus spondylitis. CONCLUSION Aspergillus spondylitis should be suspected when multiple disk levels are involved with skip lesions or subligamentous spread on MRI. A serrated appearance of the vertebral endplates and subchondral T2 hypointensity are suggestive of Aspergillus spondylitis.