Dynamic thiol/disulphide balance in patients undergoing hypotensive anesthesia in elective septoplasties.
We aimed to investigate the effects of hypotensive anaesthesia on oxidative stress with serum thiol/disulphide balance in patients undergoing elective septoplasty procedures under general anaesthesia. Seventy-two patients between the ages of 18-60, with a physical condition I -II, according to the American Society of Anesthesiologists, were included in this prospective observational study. Septoplasty was chosen for standard surgical stress. According to the maintenance of anaesthesia, patients were divided into the groups as Hypotensive Anaesthesia (n = 40) and Normotensive Anaesthesia (n = 32). Serum thiol/disulphide levels were measured by the method developed by Erel & Neşelioğlu. The native thiol and total thiol values of both groups measured at the 60th min intraoperatively were significantly lower than the preoperative values (both P < .01). Intraoperatively, at the 60th min, there was no significant difference in terms of post-native thiol and post-total thiol levels between hypotensive and normotensive anaesthesia groups (P = .68 and .81, respectively). Age >40 years and female gender were found to have a significant effect on dynamic oxidative stress (P = .002 and .001, respectively). This pilot study has found that hypotensive anaesthesia had no adverse effect on dynamic thiol/disulphide balance in elective surgeries.


Teen Dating Violence (Physical and Sexual) Among US High School Students: Findings From the 2013 National Youth Risk Behavior Survey.
National estimates of teen dating violence (TDV) reveal high rates of victimization among high school populations. The Centers for Disease Control and Prevention's national Youth Risk Behavior Survey has provided often-cited estimates of physical TDV since 1999. In 2013, revisions were made to the physical TDV question to capture more serious forms of physical TDV and to screen out students who did not date. An additional question was added to assess sexual TDV. To describe the content of new physical and sexual TDV victimization questions first administered in the 2013 national Youth Risk Behavior Survey, to share data on the prevalence and frequency of TDV (including the first-ever published overall "both physical and sexual TDV" and "any TDV" national estimates using these new questions), and to assess associations of TDV experience with health-risk behaviors. Secondary data analysis of a cross-sectional survey of 9900 students who dated, from a nationally representative sample of US high school students, using the 2013 national Youth Risk Behavior Survey. Two survey questions separately assessed physical and sexual TDV; this analysis combined them to create a 4-level TDV measure and a 2-level TDV measure. The 4-level TDV measure includes "physical TDV only," "sexual TDV only," "both physical and sexual TDV," and "none." The 2-level TDV measure includes "any TDV" (either or both physical and sexual TDV) and "none." Sex-stratified bivariate and multivariable analyses assessed associations between TDV and health-risk behaviors. In 2013, among students who dated, 20.9% of female students (95% CI, 19.0%-23.0%) and 10.4% of male students (95% CI, 9.0%-11.7%) experienced some form of TDV during the 12 months before the survey. Female students had a higher prevalence than male students of physical TDV only, sexual TDV only, both physical and sexual TDV, and any TDV. All health-risk behaviors were most prevalent among students who experienced both forms of TDV and were least prevalent among students who experienced none (all P < .001). The 2013 TDV questions allowed for new prevalence estimates of TDV to be established that represent a more complete measure of TDV and are useful in determining associations with health-risk behaviors among youth exposed to these different forms of TDV.


A single multilocus sequence typing (MLST) scheme for seven pathogenic Leptospira species.
The available Leptospira multilocus sequence typing (MLST) scheme supported by a MLST website is limited to L. interrogans and L. kirschneri. Our aim was to broaden the utility of this scheme to incorporate a total of seven pathogenic species. We modified the existing scheme by replacing one of the seven MLST loci (fadD was changed to caiB), as the former gene did not appear to be present in some pathogenic species. Comparison of the original and modified schemes using data for L. interrogans and L. kirschneri demonstrated that the discriminatory power of the two schemes was not significantly different. The modified scheme was used to further characterize 325 isolates (L. alexanderi [n = 5], L. borgpetersenii [n = 34], L. interrogans [n = 222], L. kirschneri [n = 29], L. noguchii [n = 9], L. santarosai [n = 10], and L. weilii [n = 16]). Phylogenetic analysis using concatenated sequences of the 7 loci demonstrated that each species corresponded to a discrete clade, and that no strains were misclassified at the species level. Comparison between genotype and serovar was possible for 254 isolates. Of the 31 sequence types (STs) represented by at least two isolates, 18 STs included isolates assigned to two or three different serovars. Conversely, 14 serovars were identified that contained between 2 to 10 different STs. New observations were made on the global phylogeography of Leptospira spp., and the utility of MLST in making associations between human disease and specific maintenance hosts was demonstrated. The new MLST scheme, supported by an updated MLST website, allows the characterization and species assignment of isolates of the seven major pathogenic species associated with leptospirosis.


The clinical significance and management of fever in acute myelocytic leukemia.
In order to optimize the clinical management of fever in acute myelocytic leukemia (AML), our experience with febrile patients during two therapy periods was reviewed. A structured approach to the management of fever was then devised and evaluated during a third period. Among a total of 104 patients with AML, 77 were febrile at presentation. Only agranulocytic patients (15%) had severe infection, while 43% had localized sites which responded to specific antibiotic therapy. The remainder (42%) had fever functionally attributed to leukemia. In contrast, life-threatening infection occurred in most patients (90%) after antileukemic treatment was begun. During the trial therapy period, the empiric use of carbenicillin-gentamicin for fever greater than or equal to 101 degree F during aplasia reduced the incidence of sepsis from 90 to 30% and of bacteremia from 50 to 23%. The fall in the incidence of blood and localized site cultures positive for Pseudomonas aeruginosa from 65 to 15% corresponded to a reduction in the number of distinct organisms per site from 1.6 to 1.0. These data suggest that hematogenously born invasion of infected sites by endogenous organisms has been prevented. Aplastic patients with fever responded to therapy by defervescing (54%) or improving clinically (34%). Stopping antibiotics once started while evaluating persistent fever was detrimental. Although the early empiric use of amphotericin B reduced the incidence of fungemia, its proper use in fever management is yet to be determined.


MareyMap Online: A User-Friendly Web Application and Database Service for Estimating Recombination Rates Using Physical and Genetic Maps.
Given the importance of meiotic recombination in biology, there is a need to develop robust methods to estimate meiotic recombination rates. A popular approach, called the Marey map approach, relies on comparing genetic and physical maps of a chromosome to estimate local recombination rates. In the past, we have implemented this approach in an R package called MareyMap, which includes many functionalities useful to get reliable recombination rate estimates in a semi-automated way. MareyMap has been used repeatedly in studies looking at the effect of recombination on genome evolution. Here, we propose a simpler user-friendly web service version of MareyMap, called MareyMap Online, which allows a user to get recombination rates from her/his own data or from a publicly available database that we offer in a few clicks. When the analysis is done, the user is asked whether her/his curated data can be placed in the database and shared with other users, which we hope will make meta-analysis on recombination rates including many species easy in the future.


Edge-defect induced spin-dependent Seebeck effect and spin figure of merit in graphene nanoribbons.
By using the first-principle calculations combined with the non-equilibrium Green's function approach, we have studied spin caloritronic properties of graphene nanoribbons (GNRs) with different edge defects. The theoretical results show that the edge-defected GNRs with sawtooth shapes can exhibit spin-dependent currents with opposite flowing directions by applying temperature gradients, indicating the occurrence of the spin-dependent Seebeck effect (SDSE). The edge defects bring about two opposite effects on the thermal spin currents: the enhancement of the symmetry of thermal spin-dependent currents, which contributes to the realization of pure thermal spin currents, and the decreasing of the spin thermoelectric conversion efficiency of the devices. It is fortunate that applying a gate voltage is an efficient route to optimize these two opposite spin thermoelectric properties towards realistic device applications. Moreover, due to the existence of spin-splitting band gaps, the edge-defected GNRs can be designed as spin-dependent Seebeck diodes and rectifiers, indicating that the edge-defected GNRs are potential candidates for room-temperature spin caloritronic devices.


Synthesis and characterization of a novel cationic polymer gene delivery vector.
Non-viral vectors have been widely used in gene transfection. However, its drawbacks limit its applications. In this study, a novel cationic polymer was developed as a DNA condensing agent for systemic gene delivery. Its transfection efficiency, cytotoxicity, and biocompatibility were also evaluated. Sofast, novel cationic polymer of branched polyethlenimine, was constructed by chemical methods. Its diameter, zeta potential, nucleic acid binding ability, and anti-nuclease ability were detected by electron microscopy and gel electrophoresis. In vitro, the efficiency of transfection was measured by comparing it with other gene vectors in different cell lines. MTT assay was performed to determine cytotoxicity. The compatibility of Sofast gene vector in the serum and its stability were investigated. Mouse, guinea pig and rabbit were used to process the toxic, allergenic, and pyrogenic properties of the vector in vivo. The in vivo expression was performed in the guinea pig. The results from an in vitro assay proved that the Sofast gene vector had a higher transfection efficiency than other gene vectors in a variety of primary cell cultures and transformed cell lines. The cytotoxicity assay showed a lower cytotoxicity and the cellular survival rate was >90%. The Sofast gene vector possessed compatibility with the serum and was fit to be transported at normal temperature. The results from in vivo tests indicated that the Sofast gene vector had greatly lower cytotoxicity, better biocompatibility, and higher transfection efficiency compared with other gene vectors. Because the Sofast gene vector had higher transfection efficiency, lower cytotoxicity and better compatibility than other gene vectors, it could be used for gene transfection both in vitro and in vivo.


Development and use of genetic system to identify genes required for efficient low-temperature growth of Psychrobacter arcticus 273-4.
We describe the development of genetic tools (electroporation, conjugation, vector for targeted gene replacement) for use in the psychrophile Psychrobacter arcticus 273-4 to test hypotheses about cold adaptation. Successful electroporation only occurred with nonstandard parameters, such as: electrocompetent cells freshly prepared from stationary-phase cultures, high field strengths (25 kV cm(-1)), long recovery times (16-24 h), and selection with low concentrations of antibiotics. Transformation frequencies were greatly affected by a methylation-dependent restriction barrier homologous to DpnI. The vector pJK100 (which was self-transmissible and contained a Pir-dependent R6K origin of replication) proved effective as a suicide plasmid that could be used to recombine mutations into the P. arcticus 273-4 genome. We used this vector for targeted replacement of dctT, the substrate-binding periplasmic subunit of a TRAP (tripartite ATP-independent periplasmic) transporter (which we have named dctTUF), as it was more highly expressed at cold temperatures. The replacement of dctT (with kan) decreased the rate of growth at low temperatures in mineral medium with glutamate, acetate, butyrate, and fumarate, but not with pyruvate suggesting that DctTUF participates in the transport of glutamate, acetate, butyrate, and fumarate at cold temperatures. This is the first report to demonstrate the creation of site-specific mutants in the genus Psychrobacter, their affect on low-temperature growth, and a substrate range for TAXI proteins of TRAP transporters.


[Mechanism of action of etimizol on the energy metabolism of the neurogenically damaged myocardium].
Ethimizol in a dose of 10 mg/kg prevents the decrease of calcium and creatine phosphate content in the myocardium of rats exposed to electrical stimulation. The drug was shown to exert a stimulant action on the heart adenyl cyclase system. It is suggested that the action mode of ethimizol on myocardial energy metabolism is connected with an activation of the adenyl cyclase system followed by the increased plasma membrane cell permeability by calcium ions.


Sound-driven single-electron transfer in a circuit of coupled quantum rails.
Surface acoustic waves (SAWs) strongly modulate the shallow electric potential in piezoelectric materials. In semiconductor heterostructures such as GaAs/AlGaAs, SAWs can thus be employed to transfer individual electrons between distant quantum dots. This transfer mechanism makes SAW technologies a promising candidate to convey quantum information through a circuit of quantum logic gates. Here we present two essential building blocks of such a SAW-driven quantum circuit. First, we implement a directional coupler allowing to partition a flying electron arbitrarily into two paths of transportation. Second, we demonstrate a triggered single-electron source enabling synchronisation of the SAW-driven sending process. Exceeding a single-shot transfer efficiency of 99%, we show that a SAW-driven integrated circuit is feasible with single electrons on a large scale. Our results pave the way to perform quantum logic operations with flying electron qubits.


Nur77 family of nuclear hormone receptors.
Among the numerous steroidal and orphan nuclear receptors encoded within mammalian genomes, several are involved in the regulation of apoptosis. The authors review here recent studies on members of the Nur77 family of orphan receptors including Nur77, Nurr1 and Nor-1. These transcription factors were initially identified in nerve cells, but also play key roles in the development and the effector functions of T lymphocytes and other cells and tissues. Nur77 can also act as a modulator of transcription for other orphan steroid receptors. Regulation of the Nur77 orphan receptor family members are tightly associated with transcriptional co-factors including co-repressors and co-activators. Also, one interesting aspect of the Nur77 orphan receptor family members is that depending on its location in the mitochondria or nucleus, these orphan receptors exhibit differential roles in determining cell death or cell growth. Numerous studies demonstrated the importance of Nur77 subfamily members in regulations of early embryogenesis, thymocyte negative selection, gene expression in hypothalamic-pituitary adrenal axis, chronic inflammatory response, and vascular smooth muscle cell proliferation. This review intends to integrate the importance of nuclear receptors in health and disease, and as potential targets for drug discovery by comparing the difference and similarity in the biochemical mechanisms of action used by the classic steroid/endocrine receptors and the orphan receptors to lead to identification of novel targets in manipulating the transcriptional functions and physiologic pathways for the orphan nuclear receptors.


Bladder cancer in Africa: update.
Carcinoma of the bladder is the most prevalent cancer in Egypt and in most African countries. At the National Cancer Institute (NCI), Cairo, it constitutes 30.3% of all cancers. The median age at diagnosis is 46 years, with a male preponderance of 5:1. Whether in Egypt or other African countries such as Sudan, Kenya, Uganda, Gold Coast, and Senegal, it is mostly of the squamous cell type, and arises in a background of schistosomiasis or bilharziasis. Tumors are usually advanced at the time of presentation. Bladder carcinogenesis is probably related to bacterial and human papilloma virus (HPV) infections, usually associated with bilharzial infestation. Management is mainly surgery, with 5-year survival rates after radical cystectomy increasing from 35% in the 1970s to 48% in the 1990s. The addition of adjuvant and neoadjuvant radiotherapy and chemotherapy to surgery since 1976 significantly improved both disease-free and overall survival rates. Molecular genetic studies concerning potential prognostic markers, tumorigenesis, and tumor progression in bilharzial bladder cancer are limited. However, a comprehensive detailed analysis of these factors is underway. Bilharzial bladder cancer is a preventable malignant disease. Primary prevention could be possible if the parasite is eliminated nationwide. Chemoprevention using retinoids or cyclooxygenase 2 (COX-2) inhibitors is a possible alternative. Semin Oncol 28:174-178.


Deoxyribonuclease I in mammalian tissues. Specificity of inhibition by actin.
Enzymes of the DNase I class, similar to bovine pancreatic DNase I with respect to molecular weight and ionic and pH requirements, were found in various tissues of the rat. Their analysis was facilitated by a method for detection of nucleases in crude extracts after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and subsequent renaturation of the enzymes. High levels of DNase I were found in digestive tissues, such as the parotid and submaxillary salivary glands and the lining of the small intestine., Appreciable levels were present in the lymph node, kidney, heart, prostate gland, and seminal vesicle. No activity was found in pancreatic extracts. However, under some conditions, tissues rich in proteases gave poor recovery of DNase I. Fourteen other tissues showed little or no DNase I. Inhibition of various DNase I enzymes by rabbit muscle actin was examined both in gels and in solution. Actin inhibited the bovine parotid DNase I as well as the bovine pancreatic enzyme, but actin did not inhibit any of the DNase I enzymes of the rat. This species specificity of actin inhibition makes it unlikely that the very strong association between monomeric actin and bovine DNase I is of general significance for cellular function.


Posttraumatic stress disorder in peacekeepers: a meta-analysis.
A meta-analysis was conducted to estimate the prevalence of posttraumatic stress disorder (PTSD) among peacekeepers. A systematic review was carried out using Medline, Institute for Scientific Information/Web of Science and Published International Literature on Traumatic Stress databases, leading to a total of 12 studies reporting PTSD estimates. Pooled current PTSD prevalence was 5.3%, ranging from 0.05% to 25.8%, and a metaregression was used to investigate the variables that could account for the lack of homogeneity. However, none of the extracted information was capable of explaining the heterogeneity of the estimates. Peacekeeping studies presented different methodologies such as several screening instruments and different times from the deployment to the moment of PTSD assessment. The wide difference found among those estimates highlights the importance of the creation of standards for PTSD evaluation among peacekeepers.


Predicting protein-protein interface residues using local surface structural similarity.
Identification of the residues in protein-protein interaction sites has a significant impact in problems such as drug discovery. Motivated by the observation that the set of interface residues of a protein tend to be conserved even among remote structural homologs, we introduce PrISE, a family of local structural similarity-based computational methods for predicting protein-protein interface residues. We present a novel representation of the surface residues of a protein in the form of structural elements. Each structural element consists of a central residue and its surface neighbors. The PrISE family of interface prediction methods uses a representation of structural elements that captures the atomic composition and accessible surface area of the residues that make up each structural element. Each of the members of the PrISE methods identifies for each structural element in the query protein, a collection of similar structural elements in its repository of structural elements and weights them according to their similarity with the structural element of the query protein. PrISEL relies on the similarity between structural elements (i.e. local structural similarity). PrISEG relies on the similarity between protein surfaces (i.e. general structural similarity). PrISEC, combines local structural similarity and general structural similarity to predict interface residues. These predictors label the central residue of a structural element in a query protein as an interface residue if a weighted majority of the structural elements that are similar to it are interface residues, and as a non-interface residue otherwise. The results of our experiments using three representative benchmark datasets show that the PrISEC outperforms PrISEL and PrISEG; and that PrISEC is highly competitive with state-of-the-art structure-based methods for predicting protein-protein interface residues. Our comparison of PrISEC with PredUs, a recently developed method for predicting interface residues of a query protein based on the known interface residues of its (global) structural homologs, shows that performance superior or comparable to that of PredUs can be obtained using only local surface structural similarity. PrISEC is available as a Web server at http://prise.cs.iastate.edu/ Local surface structural similarity based methods offer a simple, efficient, and effective approach to predict protein-protein interface residues.


Prospective surface marker-based isolation and expansion of fetal endothelial colony-forming cells from human term placenta.
The term placenta is a highly vascularized tissue and is usually discarded upon birth. Our objective was to isolate clinically relevant quantities of fetal endothelial colony-forming cells (ECFCs) from human term placenta and to compare them to the well-established donor-matched umbilical cord blood (UCB)-derived ECFCs. A sorting strategy was devised to enrich for CD45-CD34+CD31Lo cells prior to primary plating to obtain pure placental ECFCs (PL-ECFCs) upon culture. UCB-ECFCs were derived using a well-described assay. PL-ECFCs were fetal in origin and expressed the same cell surface markers as UCB-ECFCs. Most importantly, a single term placenta could yield as many ECFCs as 27 UCB donors. PL-ECFCs and UCB-ECFCs had similar in vitro and in vivo vessel forming capacities and restored mouse hind limb ischemia in similar proportions. Gene expression profiles were only minimally divergent between PL-ECFCs and UCB-ECFCs, probably reflecting a vascular source versus a circulating source. Finally, PL-ECFCs and UCB-ECFCs displayed similar hierarchies between high and low proliferative colonies. We report a robust strategy to isolate ECFCs from human term placentas based on their cell surface expression. This yielded much larger quantities of ECFCs than UCB, but the cells were comparable in immunophenotype, gene expression, and in vivo functional ability. We conclude that PL-ECFCs have significant bio-banking and clinical translatability potential.


Comprehensive Analysis of Regulated Cell Death in Intracranial Aneurysms.
Abnormalities in regulated cell death (RCD) are involved in multiple diseases. However, the role of RCD in intracranial aneurysms (IA) remains unknown. The aim of this study was to explore different RCD processes in the pathogenesis of IA. Four microarray datasets (GSE75436, GSE54083, GSE13353, GSE15629) and one RNA sequencing (RNA-seq) dataset (GSE122897) were extracted from the Gene Expression Omnibus (GEO) database. The microarray datasets were merged to form the training set, while the RNA-seq dataset was used as the validation set. Differentially expressed genes (DEGs), gene set enrichment analysis (GSEA), and gene set variation analysis (GSVA) were used to investigate the role of different types of RCD, including apoptosis, necroptosis, autophagy, ferroptosis and pyroptosis in the formation of IA. A novel cell death classification system for IA was established using an unsupervised consensus clustering algorithm based on cell death signature genes. Differences in functional enrichment, cell death-related regulators, and immune infiltration between two cell death clusters were evaluated. Finally, predictive genes were identified using the least absolute shrinkage and selection operator (LASSO) regression, random forest and logistic regression, allowing a prediction model to be constructed for IA rupture. Multiple RCD processes were significantly activated in IAs compared to controls. A total of 33 signature genes related to cell death were identified. The IA samples were divided into two clusters based on the cell death signature. The cell death-high subtype had a relatively higher rate of rupture, and higher enrichment levels for multiple cell death processes and several signal transduction and immune-related pathways. Immune infiltration analysis showed that cell death scores were correlated with multiple immune cell types, including macrophages, mast cells, T cells and B cells. A six-gene prediction model was constructed to predict rupture. The area under curves (AUCs) for predicting rupture in the training and validation cohorts were 0.924 and 0.855, respectively. Comprehensively analysis of RCD in IA and found that multiple RCD types are likely to be involved in IA formation and rupture. These cell death processes were correlated with inflammation and immunity. We present novel insights into the mechanism of IA pathogenesis that should help to guide further research.


Cyclic compression loaded on cartilage explants enhances the production of reactive oxygen species.
Although mechanical forces are an essential factor in the regulation of cartilage metabolism, the precise mechanisms involved have not yet been determined. We previously demonstrated that mechanical forces on chondrocytes inhibited proteoglycan (PG) synthesis. We also demonstrated the induction of reactive oxygen species (ROS) is loaded on the chondrocytes. Our purpose was to determine the ROS induction with mechanical compression and its involvement in PG synthesis of cartilage slices. Bovine articular cartilage slices were subjected to cyclic compression loading. Synthesis of PG and ROS was measured using Na2[35S]-SO4 and a chemiluminescent probe, respectively. The induction of nitrotyrosine was determined using immunohistochemistry. The synthesis of PG was significantly inhibited with 2.0 MPa of compression stress; 1 h of compression was sufficient to inhibit PG synthesis. The ROS inhibitor ebselen reversed the compression-inhibited synthesis of PG. Compression on the cartilage induced synthesis of ROS and the expression of nitrotyrosine. Mechanical compression at 2.0 MPa inhibited PG synthesis by cartilage explants. ROS were involved in this action.


Corticomuscular cross-recurrence analysis reveals between-limb differences in motor control among individuals with ACL reconstruction.
Surgical reconstruction of the anterior cruciate ligament (ACL) and subsequent physical therapy can help athletes return to competition; however, re-injury rates remain disproportionately high due, in part, to lingering biomechanical and neurological factors that are not fully addressed during rehabilitation. Prior reports indicate that individuals exhibit altered electrical activity in both brain and muscle after ACL reconstruction (ACLR). In this investigation, we aimed to extend existing approaches by introducing a novel non-linear analysis of corticomuscular dynamics, which does not assume oscillatory coupling between brain and muscle: Corticomuscular cross-recurrence analysis (CM-cRQA). Our findings indicate that corticomuscular dynamics vary significantly between involved (injured) and uninvolved legs of participants with ACLR during voluntary isometric contractions between the brain and both the vastus medialis and lateralis. This finding points to a potential lingering neural deficit underlying re-injury for athletes after surgical reconstruction, namely the dynamical structure of neuromuscular (brain to quad muscle) coordination, which is significantly asymmetric, between limbs, in those who have ACLR.


Evaluation of Adverse Events in Total Disc Replacement: A Meta-Analysis of FDA Summary of Safety and Effectiveness Data.
Systematic review and meta-analysis. The safety of new technology such as cervical total disc replacement (TDR) is of paramount importance and is best evaluated in randomized clinical trials (RCT). We compared complication risks of TDR to fusion using data from Investigational Device Exemptions. A systematic review of FDA Summary of Safety and Effectiveness reports of the 8 approved cervical TDRs was performed. These were all randomized controlled trials comparing anterior cervical discectomy and fusion (ACDF) to TDR. Important outcome variables were dysphagia, wound infection, neurologic injuries, heterotopic ossification, death, and secondary surgeries. A random effects model was selected a priori. Data on adverse events was abstracted and analyzed by calculating relative risk of ACDF to TDR by meta-analysis techniques. The study included 3027 patients with 1377 randomized to ACDF and 1652 to TDR. No statistical differences were present between the 2 groups in dysphagia/dysphonia, hardware related, heterotopic ossification, death, and overall neurologic adverse events and incidence of neurologic deterioration. The relative risk of wound-related problems ACDF to TDR was 0.76 (95% confidence interval [CI] = 0.59, 0.98) favoring ACDF, which was statistically significant, but these were minor and never required a second surgical procedure for deep wound infection. The relative risk of ACDF to TDR in surgical-related neurologic events and secondary surgeries was 1.62 (95% CI = 1.04, 2.53) and 1.79 (95% CI = 1.17, 2.74), both favoring TDR. Cervical TDR appears to be as safe as or safer than ACDF at 2-year follow-up.


Hemodynamic and biochemical effects of 100% oxygen breathing in humans.
High concentrations of inspired oxygen have been reported to have significant hemodynamic effects that may be related to increased free radical production. If oxygen therapy increases free radical production, it may also modify hemodynamic responses to a nitric oxide donor. Twenty-nine healthy male volunteers were studied using randomized, double-blind, placebo-controlled, crossover designs to determine whether oxygen therapy is associated with hemodynamic and forearm vascular effects. We measured hemodynamic parameters and forearm vascular responses before and 1 h after exposure to 100% oxygen versus medical air. Plasma 8-iso-PGF2alpha and plasma vitamin C were measured to assess the biochemical effects of oxygen administration. Hemodynamic measurements were also made following the acute administration of sublingual nitroglycerin. Oxygen therapy caused no significant change in blood pressure, plasma 8-iso-PGF2alpha, or vitamin C. Oxygen did cause a significant reduction in heart rate and forearm blood flow, and an increase in peripheral vascular resistance. Oxygen caused no change in the hemodynamic response to nitroglycerin. Therefore, in healthy young adults, therapy with 100% oxygen does not affect blood pressure, despite causing an increase in vascular resistance, is not associated with evidence of increased free radical injury, and does not affect the hemodynamic responses to nitroglycerin.


[Methodology and applicability of seroepidemiological surveys].
Seroepidemiological surveys can be defined as seroepidemiological studies carried out in population samples to investigate immunity levels against vaccinable and not vaccinable diseases. The objective of this paper is to present the methodology and applicability of serological surveys. Problems related to seroepidemiological surveys in immigrant population are also discussed. Seroepideniological surveys should be developed in representative samples of the population, determining the sample size taking into account the sample error and precision that should be obtained for population parameters. It is necessary to develop an adequate questionnaire to collect sociodemographical and medical information from all participants. Serological tests should sensitive and specific. Seroepidemiological surveys can be used assess immunity levels in different population groups, and to detect sociodemographical and medical variables associated with the immunity, vaccination and infectious diseases.


Experimental study on corrosion resistance of coiled tubing welds in high temperature and pressure environment.
Coiled tubing (CT) has been widely used for oil and gas exploitation, however corrosion of CT under high pressure and high temperature (HPHT) environment was often reported, also corrosion induced failures of CT welds were often observed to occur during service. Corrosion related behaviors of CT welds are not clear. Therefore, a study of the corrosion resistance of CT welds under HPHT environment is carried out. In order to efficiently evaluate the corrosion resistance of welds, some test samples were obtained by linear cutting out of a CT110 in service on the site. The water samples from gas field were used as the test reagent to simulate the actual corrosive medium. Based on the results of weight loss test under HPHT corrosive environment and tensile test under room conditions, the corrosion sensitivities of the welding seam and base material under various temperatures and partial pressures of CO2 as well as the mechanical properties of the corroded CT were compared and evaluated quantitatively, the corrosion morphologies and material products of the test samples were analyzed by scanning electron microscope (SEM). The test results showed that the corrosion rates of the welding seam in a HPHT caldron were 1.7, 2.0 and 1.2 times of the base metal's when the total pressure is 4MPa, and the temperature is 30°C, 60°C and 90°C, respectively. The corrosion rates of the welding seam is 2.0, 2.1 and 2.0 times of the base metal's when the partial pressure of CO2 is 0.1MPa, 0.2MPa and 0.3MPa, respectively. The yield strength of the weld seam after corrosion test was found to be reduced by 4.8% (the yield strength of the base metal was reduced by 4.0%) and its tensile strength was reduced by 8.2% (the base metal was reduced by 7.1%). This indicates that CT weld seam is more susceptible to corrosion than CT base material under service condition.


Understanding the complexities of Bluetooth for representing real-life social networks: A methodology for inferring and validating Bluetooth-based social network graphs.
Bluetooth (BT) data has been extensively used for recognizing social patterns and inferring social networks, as BT is widely present in everyday technological devices. However, even though collecting BT data is subject to random noise and may result in substantial measurement errors, there is an absence of rigorous procedures for validating the quality of the inferred BT social networks. This paper presents a methodology for inferring and validating BT-based social networks based on parameter optimization algorithm and social network analysis (SNA). The algorithm performs edge inference in a brute-force search over a given BT data set, for deriving optimal BT social networks by validating them with predefined ground truth (GT) networks. The algorithm seeks to optimize a set of parameters, predefined considering some reliability challenges associated to the BT technology itself. The outcomes show that optimizing the parameters can reduce the number of BT data false positives or generate BT networks with the minimum amount of BT data observations. The subsequent SNA shows that the inferred BT social networks are unable to reproduce some network characteristics present in the corresponding GT networks. Finally, the generalizability of the proposed methodology is demonstrated by applying the algorithm on external BT data sets, while obtaining comparable results.


Frequency of fish intake and diabetes among adult Indians.
Recent studies have shown that the choice of foods plays a role in diabetes prevention. However, little empirical evidence on this association exists in developing countries. We aimed to examine the association between frequency of fish intake and self-reported diabetes status among adult men and women in India. Analysis of cross-sectional data from participants in India's third National Family Health Survey conducted during 2005-2006 was performed. Associations between fish intake, determined by frequency of consumption (daily, weekly, occasionally, and never), and self-reported diabetes were estimated using multivariable-adjusted models in 99,574 women, 56,742 men, and 39,257 couples aged 20-49 years after adjusting for frequency of consumption of other food items, body mass index (BMI) status, tobacco smoking, alcohol drinking, watching television, age, education, living standard of the household, and place of residence. After adjustment for other dietary, lifestyle, and socioeconomic and demographic characteristics, odds of diabetes were 2 times higher (odds ratio [OR]: 2.02; 95% confidence interval [CI], 1.59-2.57; p < 0.0001) among those who reported consuming fish daily compared to those who never consumed fish. Weekly fish intake was also associated with a higher odds of having diabetes (OR: 1.55; 95% CI, 1.25-1.93; p < 0.0001). The adjusted effect of daily fish intake on diabetes was greater among men (OR: 2.46; 95% CI, 1.66-3.65) than among women (OR: 1.72; 95% CI, 1.26-2.33). In cross-spousal sensitivity analysis, the odds of a husband having diabetes was also associated with wife's daily/weekly consumption of fish (OR: 1.36; 95% CI, 0.92-2.01) and the odds of a wife having diabetes was also associated with husband's daily/weekly consumption of fish (OR: 1.21; 95% CI, 0.87-1.68). In a large nationally representative sample of adult men and women in India, daily or weekly fish intake was positively associated with the presence of diabetes. However, this is an observational finding and uncontrolled confounding cannot be excluded as an explanation for the association. More epidemiological research with better measures of food intake and clinical measures of diabetes is needed in a developing country setting to validate the findings.


The "stone-like" pattern of autophagy in human epithelial tumors and tumor-like lesions: an approach to the clinical outcome.
Cancer cells survive the adverse conditions of the extracellular milieu, i.e., hypoxia and nutrient deprivation, through angiogenesis and anaerobic glycolysis. Yet, continuously proliferating malignant cells, having high metabolic needs, may not be fully covered by these processes and seek additional sources of energy. An alternative metabolic pathway for providing energy in tumor cells is autophagy-a self-degradation mechanism by which cells recycle their own cytoplasmic constituents. Given that the clinical impact of this phenomenon on human malignancies remains by and large unexplored, we investigated morphological patterns of autophagy primarily in breast carcinomas and, subsequently, in a series of other epithelial tumors and tumor-like lesions from various organs and cell types. The microtubule-associated protein 1 light chain 3A (MAP1-LC3A) antibody and a standard immunohistochemical technique were used. Three main patterns of autophagic activity were recognized: diffuse cytoplasmic, cytoplasmic/juxta-nuclear and "stone-like" structures (SLS); the latter are dense, spheroidal, amorphous structures, of 5 microm average size, typically enclosed within cytosolic vacuoles. Normal tissues, in the proximity of malignant tumors, and tumorlike lesions expressed with remarkable consistency the cytoplasmic and the juxta-nuclear pattern, but were deprived of SLS. Interestingly, tumors having a substantial number of SLS were of high grade and unfavorable prognosis, whereas those with juxta-nuclear accumulation of LC3A protein were associated with an improved survival. Prognosis was unaffected by the diffuse cytoplasmic pattern. It is concluded that immunohistochemical staining for LC3A is a suitable method for detecting autophagy in human tissues by light microscopy, but the significance of the various patterns described needs further evaluation.


Receipt of prevention services among HIV-infected men who have sex with men.
Unprotected sexual intercourse remains a primary mode of HIV transmission in the United States. We found that receipt of services to reduce HIV transmission-risk behaviors was low among 3787 HIV-infected individuals and that men who have sex with men were especially unlikely to receive these services even though they were more likely to report unprotected sexual intercourse with seronegative and unknown serostatus casual partners. Greater efforts should be made to ensure that prevention counseling is delivered to all HIV-infected persons, especially men who have sex with men.


Cerebrospinal fluid HIV RNA and drug levels with combination ritonavir and saquinavir.
Combination antiretroviral therapy with ritonavir and saquinavir has established potent and durable activity on plasma viremia. CNS HIV infection may be sequestered from drug therapy that does not penetrate the blood-brain barrier. Penetration of these protease inhibitors into the cerebrospinal fluid (CSF) and CSF HIV RNA levels on such therapy has not been well described. In a cross-sectional study, 28 HIV1-infected study subjects were evaluated either before initiation of or before maximal response to ritonavir-saquinavir therapy, during maximal plasma virologic response, and after virologic failure. Simultaneous samples of plasma and cerebrospinal fluid were obtained from 24 study subjects to measure HIV RNA and protease inhibitor levels. Across the treatment groups, a strong correlation was found between plasma and CSF HIV RNA levels (r = 0.870; p < .001). In each study subject with plasma HIV RNA levels below assay limit (80 copies/ml), the CSF HIV RNA level was also below the limit of quantitation. Low levels of saquinavir (<2 ng/ml) and ritonavir (<25 ng/ml) in the CSF were observed, with a CSF:plasma drug concentration ratio of < or = 0.005 (0.5%) in all study subjects evaluated (n = 11). The plasma:CSF HIV RNA ratio was high before or early in treatment (median, 38; interquartile range [IQR], 13,97), but low (median, 0.29; IQR, 0.17, 7.5) in those failing therapy (group C, p < .001). CSF ritonavir and saquinavir levels are consistent with the estimated known fraction of unbound drug in plasma (<2%). Across these treatment response groups, suppression of plasma viremia can predict low CSF HIV RNA levels. This correlation may represent HIV RNA transport and equilibrium between CSF and plasma, or it may represent CNS anti-HIV activity of protease inhibitors. The low drug levels and inverted ratio of HIV RNA in the CSF compared with plasma early in plasma virologic breakthrough suggests CSF virologic failure may contribute to failure of plasma virologic response.


Novel mechanism of tumor suppression by polarity gene discs large 1 (DLG1) revealed in a murine model of pediatric B-ALL.
Drosophila melanogaster discs large (dlg) is an essential tumor suppressor gene (TSG) controlling epithelial cell growth and polarity of the fly imaginal discs in pupal development. A mammalian ortholog, Dlg1, is involved in embryonic urogenital morphogenesis, postsynaptic densities in neurons, and immune synapses in lymphocytes. However, a potential role for Dlg1 as a mammalian TSG is unknown. Here, we present evidence that loss of Dlg1 confers strong predisposition to the development of malignancies in a murine model of pediatric B-cell acute lymphoblastic leukemia (B-ALL). Using mice with conditionally deleted Dlg1 alleles, we identify a novel "pre-leukemic" stage of developmentally arrested early B-lineage cells marked by preeminent c-Myc expression. Mechanistically, we show that in B-lineage progenitors Dlg1 interacts with and stabilizes the PTEN protein, regulating its half-life and steady-state abundance. The loss of Dlg1 does not affect the level of PTEN mRNAs but results in a dramatic decrease in PTEN protein, leading to excessive phosphoinositide 3-kinase signaling and proliferation. Our data suggest a novel model of tumor suppression by a PDZ domain-containing polarity gene in hematopoietic cancers.


Extra intestinal influences on exhaled breath hydrogen measurements during the investigation of gastrointestinal disease.
During the clinical investigation of patients with gastrointestinal disease by exhaled breath hydrogen measurement, the occurrence of inexplicable variations in recorded hydrogen values led to a search for extra intestinal factors which were capable of adversely influencing breath hydrogen concentration and impairing the diagnostic accuracy of the test. Serial breath samples were collected from normal subjects under a variety of conditions which might occur during routine clinical study, including, hyperventilation, exercise, cigarette smoking, and carbohydrate ingestion. Breath hydrogen concentrations were consistently reduced by hyperventilation (p less than 0.01) and exercise (p less than 0.05). Cigarette smoking, in contrast, caused a marked rise in measured breath hydrogen (p less than 0.01), as did oral carbohydrate (p less than 0.05). Prior bactericidal mouthwash abolished this carbohydrate associated rise, suggesting that the hydrogen was the result of fermentation by oropharyngeal bacteria. Because, in all instances, the changes in breath hydrogen were of sufficient magnitude to interfere with data interpretation, it is recommended that these factors are eliminated, whenever possible, from conditions of study.


[Concurrent concentrated radio-chemotherapy of epidermoid cancer of the esophagus. Long-term results of a phase II national multicenter trial in 122 non-operable patients (FFCD 8803)].
Concomitant radiochemotherapy improves survival from inoperable esophageal cancer compared to radiotherapy alone. Several regimens of radiotherapy (standard or concentrated split course radiotherapy) are used, however the optimum protocol remains to be determined. The aim of this study was to analyze the efficacy and tolerance of concentrated concomitant split course radiochemotherapy. Prognostic factors as well as those positively influencing complete response were also studied. This multicentric phase II trial looked at patients with histologically proven, inoperable, squamous cell esophageal carcinoma without metastases or invasion of the tracheobronchial mucosa. Treatment included 3 cycles of chemotherapy by 5-FU continuous infusion (800 mg/m2.d D1-D5, D22-D26, D43-D47), cisplatin (70 mg/m2 D2, D23, D44) and radiotherapy 15 Gy/5d (D1-D5, D22-26, D43-D47). Efficacy was analyzed by endoscopy, biopsy and computerized axial tomography during the 12th week of treatment. The trial included 122 patients from 21 centers (110 M and 12F, mean age 63.1 +/- 8.6 years, range 40-78). In accordance with the TNM-UICC classification (1978), 8 patients were classified stage I (T1 N0), 13 stage II (T2 N0), 100 stage III (T3 and/or N1) and stage was unknown in 1 patient. Median follow-up was 63 months. Treatment was complete in half of the patients. 5 premature deaths (4.1%) were recorded over the treatment period, one of which was directly linked to the toxicity of the treatment. 16% of patients showed at least one severe side-effect. 117 patients received all 3 cycles of the treatment, 88 of them without delay, and all were evaluated. 58 (47.5% of the patients included) showed a complete response with a negative biopsy, 36 (29.5%) showed a partial response, 13 (10.7%) were stable and 10 (8.2%) showed progressive disease. The median duration of complete responses was 11.5 months. Symptomatically, dysphagia improved in 80% of the cases, performance status in 40%, and weight gain was observed in 30% of the patients with weight loss. At evaluation, oral feeding was impossible in 4 patients only and possible in 113 patients; however, endoscopic treatment of the dysphagia remained necessary in 28 patients. Median survival in the 122 patients included was 13.0 +/- 1.6 months and survival rates were 52.9, 29.8 and 12.1% at 1, 2 and 5 years, respectively. Three pretherapeutic prognostic factors influenced survival in a multivariate analysis: initial severe dysphagia (risk of premature death increased 3-fold in the first year), circumferential extension and the differentiated nature of the tumor (risk of death doubled regardless of the time delay). Factors influencing a complete clinical response were an early tumor stage, a poorly differenciated tumor in patients older than 65, and no circumferential extension. The risk of recurrence was 54.8% at 1 year in the 58 patients with complete remission. Complete circumferential extension and a well or moderately differentiated tumour influenced recurrence. This trial confirms the efficacy and good tolerance of concentrated split course radiochemotherapy in patients with inoperable esophageal cancer with a 5-year survival rate of 12%. This reinforces the need for a comparative trial (split course irradiation vs standard irradiation) such as the one currently being conducted in France.


Anthropometric Factors on Safe Distances between Popliteal Vessels to the Femur for Cerclage Wiring of the Distal Femoral Fracture: A Magnetic Resonance Imaging Study.
Background and Objectives: The proximity of the popliteal vessels in the distal femur may increase the risk of iatrogenic vascular injury during cerclage wiring. In this study, the closest location and distance of the popliteal vessels to the femur was examined using magnetic resonance imaging (MRI). The associations between anthropometric factors and the distance that would guide the placement of wires safely during surgery were also identified. Materials and Methods: We reviewed adult knee magnetic resonance images and recorded: (1) the relation and the shortest horizontal distance (d-H) from the femoral cortex to the popliteal vessels in axial images and (2) the vertical distance (d-V) from the adductor tubercle to the axial level of the d-H values in coronal images. The effects of anthropometric factors (sex, age, body height, body weight, body mass index, thigh circumference, femoral length and femoral width) on these distances were analysed. Results: Analysis of 206 knee magnetic resonance images revealed that the closet locations of popliteal vessels were at the posteromedial aspect of the femur. The d-H and d-V were 7.38 ± 3.22 mm and 57.01 ± 11.14 mm, respectively, and were both shorter in women than in men (p < 0.001). Multivariate analysis identified thigh circumference and femoral length as the most influential factors for the d-H and d-V, respectively (p < 0.001). Linear regression demonstrated a strong positive linear correlation between the thigh circumference and the d-H and between the femoral length and the d-V (Pearson's r = 0.891 and 0.806, respectively (p < 0.001)). Conclusions: The closet location and distance of the popliteal vessels to the femur provide useful information for wire placement during distal femoral fracture surgery while minimising the risk of vascular injury. Given that patients with a smaller thigh circumference and a shorter femoral length are more likely to have a smaller d-H and a shorter d-V, respectively, cautious measures should be taken in such cases.


[Search for lectin-producers among representatives of some yeast genera].
Hemagglutinating properties of the culture liquid and cells of 451 strains, 24 species, 7 genera of the museum and fresh yeast cultures have been investigated. The researchers have distinguished 333 strains (74%) capable for production of extracellular lectins and those bound to the cell surface with activity about 512-1024 hemagglutinating units. The extracellular lectins were found in 41% of lectin-synthesizing strains; the highest amount of their producers were found among representatives of genera Saccharomyces, Kluyveromyces, Cryptococcus. Strains of Debaryomyces genus mainly synthesized lectins of the bound form, and the yeast of Pichia genus--lectins of the both types. Affinity of the extracellular lectin Saccharomyces cerevisiae UCM Y-530 for D-gluconic acid has been established.


Dynamics of dynamin during clathrin mediated endocytosis in PC12 cells.
Members of the dynamin super-family of GTPases are involved in disparate cellular pathways. Dynamin1 and dynamin2 have been implicated in clathrin-mediated endocytosis. While some models suggest that dynamin functions specifically at the point of vesicle fission, evidence also exists for a role prior to fission during vesicle formation and it is unknown if there is a role for dynamin after vesicle fission. Although dynamin2 is ubiquitously expressed, dynamin1 is restricted to the nervous system. These two structurally similar endocytic accessory proteins have not been studied in cells that endogenously express both. The present study quantitatively assesses the dynamics of dynamin1 and dynamin2 during clathrin-mediated endocytosis in PC12 cells, which endogenously express both proteins. Both dynamin isoforms co-localized with clathrin and showed sharp increases in fluorescence intensity immediately prior to internalization of the nascent clathrin-coated vesicle. The fluorescence intensity of both proteins then decreased with two time constants. The slower time constant closely matched the time constant for the decrease of clathrin intensity and likely represents vesicle movement away from the membrane. The faster rate may reflect release of dynamin at the neck of nascent vesicle following GTP hydrolysis. This study analyses the role of dynamin in clathrin-mediated endocytosis in a model for cellular neuroscience and these results may provide direct evidence for the existence of two populations of dynamin associated with nascent clathrin-coated vesicles.


Impact of an emergency short stay unit on emergency department performance of poisoned patients.
This was a before and after study which sought to assess the impact of opening an ED short stay unit (ESSU) on the ED performance of poisoned patients. Data was collected from two groups of adult patients presenting to an ED with a tertiary referral inpatient Toxicology unit from the 2009 and 2012 calendar years, to assess the impact of the ESSU. The toxicology unit clinical database and hospital electronic medical records were interrogated for demographic, clinical and hospital flow details of presentations. The primary outcome was ED length of stay (LOS). Other outcomes included proportion of patients remaining in ED for their admission, 28day re-presentations and hospital LOS. During 2009, 795 patients met inclusion criteria, and during 2012, 762. The median LOS in ED was reduced from 8.5 h (IQR: 4.7-14 h) to 2.7 h (IQR: 1.6-4.6; p<0.0001). The proportion of patients remaining in ED for their entire hospital stay was reduced from 515/795 (65%) to 56/762 (7.3%) [Absolute difference: 57%; 95% CI: 53 to 62%; p<0.0001]. Total hospital LOS increased from 14.5 h (IQR: 8.4-21.8 h) to 16.7 h (IQR: 11.5-23; p<0.0001), but there was a decrease in re-presentations with self-poisoning within 28days from 6.9% in 2009 to 4.5% in 2012 (p<0.038). There was no difference between disposition destination or toxins causing exposure between the two groups. The ESSU led to a significant improvement in ED performance of poisoned patients. It also potentially assisted in reducing ED overcrowding.


Intra-articular clearance of labeled dextrans from naive and arthritic rat knee joints.
Determine the effects of arthritis on the trans-synovial clearance of small and large model compounds following local delivery to the knee joint in a rat model. Intra-articular delivery was studied in rat knee joints in an osteoarthritis model of joint instability (medial collateral ligament and meniscus transection model or MMT). Fluorescently-labeled 10 kDa or 500 kDa dextran was injected in the arthritic or unoperated control (naive) joints 3 weeks after surgical destabilization, and the temporal clearance pattern was evaluated via in vivo regional fluorescence imaging, dextran concentrations in plasma and draining lymph nodes, and by quantification of fluorescence in histological synovium sections. Together these data were used to evaluate the effect of osteoarthritis and solute size on the rate of drug clearance from the joint. Clearance of 10 kDa dextran from the joint space quantified using in vivo fluorescence imaging of the knee joint region was not significantly different between naive and MMT joints. In contrast, clearance of 500 kDa dextran was significantly reduced for MMT joints when compared to naive joints by fluorescence in vivo imaging. Drug accumulation in lymph nodes and plasma were lower for the 500 kDa dextran as compared to 10 kDa dextran, and lymph node levels were further reduced with the presence of osteoarthritis. Furthermore, synovium was significantly thicker in MMT joints than in naive joints and image analysis of joint tissue sections revealed different trans-synovial distributions of 10 and 500 kDa dextran. Large macromolecules were retained in the arthritic joint longer than in the healthy joint, while smaller molecules were cleared similarly in healthy and arthritic joints. In vivo fluorescence imaging, plasma and lymph node concentrations, and spatial distributions of drug fluorescence identified differences in higher molecular weight clearance between naive and arthritic disease states. Findings may relate to a thickening of synovium for joints with induced arthritis, and support the concept that intra-articular drug delivery effectiveness may vary with the state of joint pathology.


Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy.
Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date. Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl). Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.


Danish translation and psychometric testing of the Rivermead Mobility Index.
The Rivermead Mobility Index (RMI) is widely used in several neurological conditions including multiple sclerosis (MS), but its psychometric properties have not been documented in Scandinavia. Therefore, the aim of the study was to translate RMI from UK English into Danish and conduct an initial psychometric testing of the Danish RMI. The Danish translation conducted by the forward-backward method was first field-tested regarding user-friendliness and relevance. It was then psychometrically tested among 40 outpatients with MS regarding unidimensionality (corrected item-total correlations, adherence to an assumed Guttman response pattern), reliability, and construct validity. Field testing found the Danish RMI relevant and user-friendly. Corrected item-total correlations were ≥0.47 and item responses fitted the Guttman pattern. There was a 47.5% ceiling effect, and reliability was 0.91. Correlations supported construct validity. The Danish RMI is user-friendly, unidimensional, reliable, and valid. The results correspond to those previously reported with the original UK RMI version. Ceiling effects are limiting but sample related. Larger samples representing a wider variety of MS severities are needed for firmer evaluation of the Danish RMI.


Pitfalls in myocardial perfusion assessment with dynamic MR imaging after administration of a contrast material bolus in dogs.
The authors evaluated the artifacts observed on myocardial perfusion curves derived from an inversion-prepared fast gradient-echo (GRE) imaging sequence in dogs after injection of a gadolinium-based contrast agent. Six mongrel dogs were divided into three groups. In groups 1 and 2, anesthesia was maintained with pentobarbital. Group 2 also received an intravenous injection of atropine (0.03 mg/kg). In group 3, anesthesia was maintained with isoflurane (1.0%). Imaging was performed on a 1.5-T magnetic resonance (MR) imaging unit (one section per heart beat, a 30 x 15-cm field of view, 10-mm section thickness, and 64-kHz bandwidth). Region-of-interest (ROI) markers were placed on the blood pool of the left intraventricular cavity, anterior wall of the left ventricle, and anterior to the chest wall to track respiratory motion. In group 1, the signal intensity (SI) periodically increased during each inspiration due to respiratory sinus arrhythmia. The relation between the SI increase and the variation of the delay between images was demonstrated in vitro and by computer simulations. No periodic increase of the SI was observed when regular cardiac rhythm was maintained by pharmacologic inhibition of the vagal-mediated chronotropic response with either the addition of atropine to pentobarbital or the use of isoflurane as the anesthetic agent. In an inversion-prepared fast GRE sequence, respiratory sinus arrhythmia can induce periodic SI increase by varying the respiratory rate interval and delay between images.


Biased activity of soluble guanylyl cyclase: the Janus face of thymoquinone.
The natural compound thymoquinone, extracted from Nigella sativa (black cumin), is widely used in humans for its anti-oxidative properties. Thymoquinone is known for its acute endothelium-independent vasodilator effects in isolated rat aortae and pulmonary arteries, depending in part on activation of adenosine triphosphate-sensitive potassium channels and inhibition of voltage-dependent calcium channels. The compound also improves endothelial dysfunction in mesenteric arteries of ageing rodents and in aortae of rabbits treated with pyrogallol, by inhibiting oxidative stress. Serendipitously, thymoquinone was found to augment contractions in isolated arteries with endothelium of both rats and pigs. The endothelium-dependent augmentation it causes counterintuitively depends on biased activation of soluble guanylyl cyclase (sGC) producing inosine 3',5'-cyclic monophosphate (cyclic IMP) rather than guanosine 3',5'-cyclic monophosphate. This phenomenon shows a striking mechanistic similarity to the hypoxic augmentation previously observed in porcine coronary arteries. The cyclic IMP preferentially produced under thymoquinone exposure causes an increased contractility of arterial smooth muscle by interfering with calcium homeostasis. This brief review summarizes the vascular pharmacology of thymoquinone, focussing in particular on how the compound causes endothelium-dependent contractions by biasing the activity of sGC.


Position paper on the therapeutic use of rituximab in CD20-positive diffuse large B-cell non-Hodgkin's lymphoma.
The available data on rituximab in combination with chemotherapy confirm that the addition of an independently active biological agent to full-dose standard chemotherapy results in higher rates of complete response, lower rates of relapse, prolonged survival, little additional toxicity and no compromise of the dose intensity of standard chemotherapy regardless of age and risk group. Given the strength of these data, the British Committee for Standards in Haematology believes that rituximab should be available for prescription by UK haematologists and oncologists according to its licensed indication in patients with diffuse large B-cell lymphoma until further data are available to confirm or refute these results. We consider that the use of rituximab with chemotherapy in aggressive lymphoma is cost-effective and that failure to support its introduction will be strongly in conflict with professional and patient opinion.


Validation of exposure assessment and assessment of recruitment methods for a prospective cohort study of mobile phone users (COSMOS) in Finland: a pilot study.
The aim of the study was to evaluate the agreement between self-reported and operator-derived estimates of call time based on a three-month monitoring period, as well as the consistency of mobile phone use over time. Alternative approaches to improve participation in a cohort study of mobile phone users were also compared. A total of 5,400 subjects were identified from network operators' subscriber databases for recruitment to the pilot study. Operator and questionnaire data were used to quantify mobile phone use. Operator data were available for a subset of the subjects for a three-month period in three consecutive years. We also evaluated the effect of the length of the questionnaire and one- or two-phase recruitment on participation. The average response rate for both questionnaires and recruitment procedures was 12%. The response rate was not affected by the length of the questionnaire or the recruitment method.Operator data were available for 83% of the participants for 2007, the first study year. The agreement between self-reported and operator-derived call times decreased with the level of use among intermediate and heavy mobile phone users. During 2007-2009, mobile phone use increased fairly constantly over time. The agreement between self-reported mobile phone use and operator databases was moderate and overestimation of the call time by participants was common. A prospective cohort study would be feasible in Finland, although the potentially low participation rate would increase the resources required for recruitment.


Inhibitory activity of the flower buds of Lonicera japonica Thunb. against histamine production and L-histidine decarboxylase in human keratinocytes.
In previous studies we found that anionic surfactants such as sodium laurate (SL) and/or sodium dodecylsulfate (SDS) exert actions on epidermal keratinocytes rather than mast cells to give rise of histamine production and skin itching through increasing the expression of the 53-kDa active form of L-histidine decarboxylase (HDC). In addition, with treatment of SL in a three-dimensional human keratinocyte culture, increases in both the 53-kDa HDC and histamine production are detected and thus this culture assay is applied to screen anti-itching materials from natural resources. In this study, the inhibitory activity of "Kin-gin-ka" (flower buds of Lonicera japonica Thunb., FLJ) against histamine production and expression of the active form of HDC were examined in this culture assay. FLJ is a well-known traditional Chinese medicine, being used to treat fevers, coughs and some infectious diseases. The result showed both FLJ and chlorogenic acid had inhibitory activities against the expression of 53-kDa HDC and histamine production. However, chlorogenic acid showed a weaker effect on histamine production than that of FLJ, suggesting that other chemical constituents besides chlorogenic acid could contribute to the inhibitory activities. Thus, a further chemical study of FLJ is now under investigation.


Clinical utility of likelihood ratios.
Test-performance characteristics can be derived from a simple 2x2 table displaying the dichotomous relationship between a positive or negative test result and the presence or absence of a target disorder. Sensitivity and specificity, including a summary display of their reciprocal relationship as a receiver operating characteristics curve, are relatively stable test characteristics. Unfortunately, they represent an inversion of customary clinical logic and fail to tell us precisely what we wish to know. Predictive values, on the other hand, provide us with the requisite information but-because they are vulnerable to variation in disease prevalence-are numerically unstable. Likelihood ratios (LRs), in contrast, combine the stability of sensitivity and specificity to provide an omnibus index of test performance far more useful than its constituent parts. Application of Bayes' theorem to LRs produces the following summary equation: Clinically estimated pretest odds of disease x LR=Posttest odds of disease. This simple equation illustrates a concordance between the mathematical properties of likelihood ratios and the central strategy underlying diagnostic testing: the revision of disease probability.


[Performance comparison of material tests for cadmium and lead in food contact plastics].
Based on the Japanese Food Sanitation Law, the performances of official and alternative material test methods for cadmium (Cd) and lead (Pb) in food contact plastics were compared. Nineteen laboratories participated to an interlaboratory study, and quantified Cd and Pb in three PVC pellets. in the official method, a sample is digested with H2SO4, taken up in HCl, and evaporated to dryness on a water bath, then measured by atomic absorption spectrometry (AAS) or inductively coupled plasma-optical emission spectrometry (ICP-OES). Statistical treatment revealed that the trueness, repeatability (RSDr) and reproducibility (RSDr) were 86-95%, 3.1-9.4% and 8.6-22.1%, respectively. The values of the performance parameters fulfilled the requirements , and the performances met the test specifications. The combination of evaporation to dryness on a hot plate and measurement by AAS or ICP-OES is applicable as an alternative method. However, the trueness and RSDr were inferior to those of the official method. The performance parameters obtained by using the microwave digestion method (MW method) to prepare test solution were better than those of the official method. Thus, the MW method is available as an alternative method. Induced coupled plasma-mass spectrometry (ICP-MS) is also available as an alternative method. However, it is necessary to ensure complete digestion of the sample.


When is active surveillance the appropriate treatment for prostate cancer?
The incidence of prostate cancer has increased dramatically worldwide during the past few decades in part because of increased testing for prostate specific antigen (PSA). The aggressive use of this screening tool has resulted in the identification of many localized prostate cancers a majority of which are relatively low volume, low grade tumors. Older autopsy studies have documented that incidental prostate cancer is quite common especially in older men. The finasteride chemoprevention trial confirmed these findings. Many prostate cancers are not destined to progress to clinically significant tumors. Several case series have documented the natural history of clinically detected prostate cancer. The progression of disease identified by PSA testing is less certain. These studies uniformly show that many men with low grade tumors can survive for over two decades in the absence of treatment. Furthermore, randomized clinical trials have shown only a modest ten year survival advantage for those men undergoing either surgery or radiation. As a consequence, men with low risk of disease progression may wish to consider active surveillance as a treatment option. To date, several case series have documented that men following an active surveillance protocol that includes regular PSA testing and periodic re-biopsy have an excellent outcome. The majority of these men have not demonstrated evidence of progression during the first decade of follow-up and among those that have the majority have undergone either surgery or radiation without compromise of their long-term outcome. Unfortunately, until better biomarkers become available, the outcome of any individual patient defies accurate prediction. Men with newly diagnosed prostate cancer must weigh the risk of disease progression against the potential efficacy and safety of treatment when making a decision whether to consider active surveillance as an appropriate treatment.


Inferring social ties from geographic coincidences.
We investigate the extent to which social ties between people can be inferred from co-occurrence in time and space: Given that two people have been in approximately the same geographic locale at approximately the same time, on multiple occasions, how likely are they to know each other? Furthermore, how does this likelihood depend on the spatial and temporal proximity of the co-occurrences? Such issues arise in data originating in both online and offline domains as well as settings that capture interfaces between online and offline behavior. Here we develop a framework for quantifying the answers to such questions, and we apply this framework to publicly available data from a social media site, finding that even a very small number of co-occurrences can result in a high empirical likelihood of a social tie. We then present probabilistic models showing how such large probabilities can arise from a natural model of proximity and co-occurrence in the presence of social ties. In addition to providing a method for establishing some of the first quantifiable estimates of these measures, our findings have potential privacy implications, particularly for the ways in which social structures can be inferred from public online records that capture individuals' physical locations over time.


HLA haplotype is associated with diabetes among atomic bomb survivors.
We examined radiation effects on the relationship between diabetes development and genetic background in atomic-bomb (A-bomb) survivors. Our main aim in this study was to shed light on the role of genetic background in diabetes onset among A-bomb survivors by studying possible relationships between human leukocyte antigen (HLA) genotypes and the diabetes in patients and controls. We examined the effects of different HLA haplotypes on type 2 diabetes development by determining the DQA1 and DRB1 alleles of Hiroshima A-bomb survivors (111 diabetic patients and 774 controls) using the polymerase chain reaction-sequence specific oligonucleotide probes (PCR-SSOP) method. We noted an increased risk of diabetes in the higher dose group among these patients (trend p = 0.001). The risk of the most heavily exposed group was significantly higher than that of the unexposed group or the low-dose group especially in survivors with the DQA1*03-DRB1*09 or DQA1*0401-DRB1*08 haplotypes (trend p = 0.002 or p = 0.05, respectively). By contrast, in people with other haplotypes, the risk did not increase significantly with increasing dose. These results suggest that individuals with specific HLA haplotypes may have an increased risk of diabetes with increased-dose categories.


Macromolecular crowding and hydrophobic effects on Fmoc-diphenylalanine hydrogel formation in PEG : water mixtures.
A small peptide-based gelator forms stable hydrogels in an aqueous mixture with a range of poly(ethylene glycol) PEGs, from the ethylene glycol monomer to PEG 20 000 with stronger gels forming in polymeric PEG. Spectroscopic studies on these systems reveal significant secondary structural changes when compared to gels formed from pure water. The use of PEG also facilitates the incorporation and controlled release of poorly water-soluble anti-cancer drugs such as Temozolomide and Paclitaxel (Taxol®). This work provides a powerful insight into the role of macromolecular crowding and hydrophobic interactions in not only hydrogels formed from small molecules but potentially also biological gel-like materials such as the cytosol and the extracellular matrix (ECM).


Functional changes in persons aging with spinal cord injury.
Declines in general physical function and the effect of these changes on activities of daily living and needs for assistance were assessed in 150 individuals with spinal cord injury (SCI). The sample consisted of outpatients returning for follow-up at the spinal cord injury clinic at Rancho Los Amigos National Rehabilitation Center in Downey, CA. The average duration of injury of the sample was 13 years (range 1-37), and average age was 38 years (range 18-64). Twenty-four percent of those sampled experienced a decline or change in their physical function within the last 5 years. Individuals experiencing declines were significantly older than those without changes, averaging 45 years versus 36 years. The group with change also had a longer duration of injury, averaging 18 years versus 11 years compared to the group reporting no declines. Fatigue was the most frequently reported problem, followed by pain and weakness. Over half of the group with changes required additional assistance with activities of daily living (ADLs). Family members were the primary helpers for both ADLs and instrumental activities of daily living (IADLs) for those persons experiencing changes. The use of assistive technology, primarily equipment for bathing, toileting, and low technology devices, increased with time. The increased vulnerability to loss of function in persons with advancing age and duration of injury in this population with SCI suggests the need for early preventative measures, routine assessments to detect changes, and access to health care and supportive services to alleviate or minimize the effect of these changes.


The RAFT network: 5 years of distance continuing medical education and tele-consultations over the Internet in French-speaking Africa.
Continuing education of healthcare professionals is a key element for the quality and efficiency of a health system. In developing countries, this activity is usually limited to capitals, and delocalized professionals do not have access to such opportunities, or to didactic material adapted to their needs. This limits the interest of such professionals to remain active in the periphery, where they are most needed to implement effective strategies for prevention and first-line healthcare. Telemedicine tools enable the communication and sharing of medical information in electronic form, and thus facilitate access to remote expertise. A physician located far from a reference center can consult its colleagues remotely in order to resolve a difficult case, follow a continuous education course over the Internet, or access medical information from digital libraries or knowledge bases. These same tools can also be used to facilitate exchanges between centers of medical expertise: health institutions of a same country as well as across borders. Since 2000, the Geneva University Hospitals have been involved in coordinating the development of a network for eHealth in Africa (the RAFT, Réseau en Afrique Francophone pour la Télémédecine), first in Mali, and now extending to 10 French-speaking African countries. The core activity of the RAFT is the webcasting of interactive courses. These sessions put the emphasis on knowledge sharing across care professionals, usually in the form of presentations and dialogs between experts in different countries. The technology used for the webcasting works with a slow (25 kbits/s) internet connection. Other activities of the RAFT network include visioconferences, teleconsultations based on the iPath system, collaborative knowledge bases development, support for medical laboratories quality control, and the evaluation of the use of telemedicine in rural areas (via satellite connections) in the context of multisectorial development. Finally, a strong emphasis is put on the development of capacities for the creation, maintenance, and publication of quality medical didactic contents. Specific courses are organized for the national coordinators of the network to develop these competencies, with the help of the Health-On-the-Net Foundation. The richness of the plurality of knowledge and know-how must be steered towards emulation and sharing, respectful of each partner's identity and culture. Collaborations with UNESCO and WHO have been initiated to address these challenges.


Circadian clocks: It's time for chronobiology.
Circadian clocks are everywhere, yet we still have not translated the vast knowledge gained in the past 20 years on the properties of circadian clocks into practical applications. We are missing opportunities for improving quality of life, health, and sustainability.


New index to predict esophageal variceal bleeding in cirrhotic patients.
To develop a safe, simple, noninvasive and affordable system to predict esophageal variceal bleeding (EVB) in decompensated cirrhosis patients. Four hundred and eighty-six patients with decompensated cirrhosis (238 males and 248 females), with a mean age of 63.1 ± 11.2 years, were admitted to Changshu Affiliated Hospital of Suzhou University between May 2008 and March 2011. Patients enrolled in this study underwent ultrasound-Doppler (US-Doppler) to assess left gastric vein (LGV) blood flow velocity (LGVV) and blood flow direction (LGVBFD), and were evaluated by the Model For End-Stage Liver Disease (MELD) scoring system. All patients received follow-up evaluations every three months. The resulting data were entered into a database after each time point collection. Four hundred and sixteen patients completed follow-up evaluations for an average of 31.6 mo (range: 12 to 47 mo). Fifty-one (12.3%) patients experienced EVB. The change in the MELD score over three months (ΔMELD), LGVV and LGVBFD were independently associated with EVB occurrence. MELD-US-Doppler Index (MUI), a new index, was developed and calculated using the following logistic regression equation: MUI = Logit (P) = 1.667 (ΔMELD) + 2.096 (LGVV) - 3.245 (LGVBFD) - 1.697. The area under the receiver operating characteristic curve for prediction of EVB occurrence was significantly higher for the MUI [0.858 (95%CI: 0.774-0.920)] than for ΔMELD [0.734 (95%CI: 0.636-0.817); P < 0.05], LGVV [0.679 (95%CI: 0.578-0.769); P < 0.05] or LGVBFD [0.726 (95%CI: 0.627-0.810); P < 0.05] alone. When the MUI was set at 46, the index had high diagnostic accuracy (85.8%), with high specificity (80%) and sensitivity (87.27%). The MUI, a noninvasive and affordable index, can predict EVB occurrence in decompensated cirrhotic patients and serve as an alternative when conventional endoscopic screening is declined.


[An assessment of the patients in a pediatric intensive care unit].
Twenty four patients, consecutively hospitalized in the "Dr. Carlos J. Finlay" Military Hospital, Pediatric Intensive Care Unit, Havana City, were evaluated by the therapeutic intervention system (TISS), in order to extend knowledges on evaluative system. According to the clinic classification system, the cases were clustered into four classes. The most severe cases are included into class IV (higher score), while cases clustered into class I (lower score) are those under current surveillance. Ruling clinical classification corresponded to class II and IV, with seven cases in each group. Incidence of diagnosis of infection of the central nervous system, followed by intoxication, was observed. Mean index of patient/nurse score was 22.3 in the most severe cases. There was little difference between day shift (22.9 points) and night shift (24.1 points).


6-shogaol, a major compound in ginger, induces aryl hydrocarbon receptor-mediated transcriptional activity and gene expression.
Xenobiotics are usually detoxified by drug-metabolizing enzymes and excreted from the body. The expression of many of drug-metabolizing enzymes is regulated by the aryl hydrocarbon receptor (AHR). Some substances in vegetables have the potential to be AHR ligands. To search for vegetable components that exhibit AHR-mediated transcriptional activity, we assessed the activity of vegetable extracts and identified the active compounds using the previously established stable AHR-responsive HepG2 cell line. Among the hot water extracts of vegetables, the highest activity was found in ginger. The ethyl acetate fraction of the ginger hot water extract remarkably induced AHR-mediated transcriptional activity, and the major active compound was found to be 6-shogaol. Subsequently, the mRNA levels of AHR-targeting drug-metabolizing enzymes (CYP1A1, UGT1A1, and ABCG 2) and the protein level of CYP1A1 in HepG2 cells were shown to be increased by 6-shogaol. This is the first report that 6-shogaol can regulate the expression of detoxification enzymes by AHR activation.


Why does Amphibian Chytrid (Batrachochytrium dendrobatidis) not occur everywhere? An exploratory study in Missouri ponds.
The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), is a globally emerging pathogen that has caused widespread amphibian population declines, extirpations, and extinctions. However, Bd does not occur in all apparently suitable amphibian populations, even within regions where it is widespread, and it is often unclear why Bd occurs in some habitats but not others. In this study, we rigorously surveyed the amphibian and invertebrate biodiversity of 29 ponds in Missouri, screened resident amphibian larvae (Rana (Lithobates) sp.) for Bd infection, and characterized the aquatic physiochemical environment of each pond (temperature pH, conductivity, nitrogen, phosphorus, and chlorophyll-a). Our goal was to generate hypotheses toward answering the question, "Why does Bd not occur in all apparently suitable habitats?" Bd occurred in assayed amphibians in 11 of the 29 ponds in our study area (38% of ponds). We found no significant relationship between any single biotic or abiotic variable and presence of Bd. However, multivariate analyses (nonmetric multidimensional scaling and permutational tests of dispersion) revealed that ponds in which Bd occurred were a restricted subset of all ponds in terms of amphibian community structure, macroinvertebrate community structure, and pond physiochemistry. In other words, Bd ponds from 6 different conservation areas were more similar to each other than would be expected based on chance. The results of a structural equation model suggest that patterns in the occurrence of Bd among ponds are primarily attributable to variation in macroinvertebrate community structure. When combined with recent results showing that Bd can infect invertebrates as well as amphibians, we suggest that additional research should focus on the role played by non-amphibian biota in determining the presence, prevalence, and pathogenicity of Bd in amphibian populations.


Moco biosynthesis and the ATAC acetyltransferase engage translation initiation by inhibiting latent PKR activity.
Molybdenum cofactor (Moco) biosynthesis is linked to c-Jun N-terminal kinase (JNK) signaling in Drosophila through MoaE, a molybdopterin (MPT) synthase subunit that is also a component of the Ada Two A containing (ATAC) acetyltransferase complex. Here, we show that human MPT synthase and ATAC inhibited PKR, a double-stranded RNA-dependent protein kinase, to facilitate translation initiation of iron-responsive mRNA. MPT synthase and ATAC directly interacted with PKR and suppressed latent autophosphorylation of PKR and its downstream phosphorylation of JNK and eukaryotic initiation factor 2α (eIF2α). The suppression of eIF2α phosphorylation via MPT synthase and ATAC prevented sequestration of the guanine nucleotide exchange factor eIF2B, which recycles eIF2-GDP to eIF2-GTP, resulting in the promotion of translation initiation. Indeed, translation of the iron storage protein, ferritin, was reduced in the absence of MPT synthase or ATAC subunits. Thus, MPT synthase and ATAC regulate latent PKR signaling and link transcription and translation initiation.


SET/TAF1 forms a distance-dependent feedback loop with Aurora B and Bub1 as a tension sensor at centromeres.
During mitosis, spatiotemporal regulation of phosphorylation at the kinetochore is essential for accurate chromosome alignment and proper chromosome segregation. Aurora B kinase phosphorylates kinetochore substrates to correct improper kinetochore-microtubule (KT-MT) attachments, whereas tension across the centromeres inactivates Aurora B kinase, and PP2A phosphatase dephosphorylates the kinetochore proteins to stabilize the attachments. However, the molecular entity of the tension sensing mechanism remains elusive. In a previous report, we showed that centromeric SET/TAF1 on Sgo2 up-regulates Aurora B kinase activity via PP2A inhibition in prometaphase. Here we show that Aurora B and Bub1 at the centromere/kinetochore regulate both kinase activities one another in an inter-kinetochore distance-dependent manner, indicating a positive feedback loop. We further show that the centromeric pool of SET on Sgo2 depends on Bub1 kinase activity, and the centromeric localization of SET decreases in a distance-dependent manner, thereby inactivating Aurora B in metaphase. Consistently, ectopic targeting of SET to the kinetochores during metaphase hyperactivates Aurora B via PP2A inhibition, and thereby rescues the feedback loop. Thus, we propose that SET, Aurora B and Bub1 form a distance-dependent positive feedback loop, which spatiotemporally may act as a tension sensor at centromeres.


Predicting postoperative surgical site infection with administrative data: a random forests algorithm.
Since primary data collection can be time-consuming and expensive, surgical site infections (SSIs) could ideally be monitored using routinely collected administrative data. We derived and internally validated efficient algorithms to identify SSIs within 30 days after surgery with health administrative data, using Machine Learning algorithms. All patients enrolled in the National Surgical Quality Improvement Program from the Ottawa Hospital were linked to administrative datasets in Ontario, Canada. Machine Learning approaches, including a Random Forests algorithm and the high-performance logistic regression, were used to derive parsimonious models to predict SSI status. Finally, a risk score methodology was used to transform the final models into the risk score system. The SSI risk models were validated in the validation datasets. Of 14,351 patients, 795 (5.5%) had an SSI. First, separate predictive models were built for three distinct administrative datasets. The final model, including hospitalization diagnostic, physician diagnostic and procedure codes, demonstrated excellent discrimination (C statistics, 0.91, 95% CI, 0.90-0.92) and calibration (Hosmer-Lemeshow χ2 statistics, 4.531, p = 0.402). We demonstrated that health administrative data can be effectively used to identify SSIs. Machine learning algorithms have shown a high degree of accuracy in predicting postoperative SSIs and can integrate and utilize a large amount of administrative data. External validation of this model is required before it can be routinely used to identify SSIs.


Effects of inclusion of graded amounts of soya bean hulls on feed intake, chewing activity and nutrient digestibility in dairy cows.
Twelve multiparous Holstein dairy cows were used in a replicated 4 × 4 Latin square changeover design to evaluate the effects of graded inclusion of soya bean hulls (SHs) in replacement of diet forages at 0%, 10%, 20% and 30% of dietary dry matter (DM) basis on peNDF > 8 and peNDF > 1.18 contents of diets and their resulting effects on chewing activity, nutrient digestibility and milk production of dairy cattle. The control diet contained 50% forage, 50% concentrate and no SH. In the other three diets, SH was substituted for alfalfa hay, corn silage and wheat bran to supply 10%, 20% and 30% of the dietary DM. Increasing SH concentration in the diets resulted in decreasing concentrations of forage neutral detergent fibre (NDF), physically effective NDF (peNDF) and mean particle size (p < 0.01). Chewing activity per kilogram of daily dry matter intake (DMI) was not affected by the different diets tested. However, chewing activity significantly decreased for kilogram intake of NDF, but increased for peNDF > 1.18 when SH was included in the diets (p < 0.01). Total tract apparent digestibility of nutrients significantly increased for DM, organic matter (p < 0.05) and NDF (p < 0.01) but decreased for crude protein (p < 0.05) as the proportion of SH was increased in the diets. Rumen pH value of cattle was not influenced by the diets. Including medium and high amounts of SH in the diets decreased DMI of the animals (p < 0.05) without any significant effect on their daily milk or 4% fat-corrected milk production. In conclusion, the results of this study showed that the NDF from a non-forage fibre source like SH had a lower potential for stimulating chewing activity than did forage NDF. Despite this, the small size of dietary particles increased not only the chewing activity per kilogram of peNDF intake but also saliva secretion as well as the potential for rumen to neutralize acids. The findings of this study demonstrate the greater differences in peNDF > 8 among the diets and that these differences are better reflected in terms of DMI, chewing activity and nutrient digestibility, but not in rumen pH.


Natural products with anti-inflammatory and immunomodulatory activities against autoimmune myocarditis.
Myocarditis is an inflammatory disease of the myocardium associated with immune dysfunction which may frequently lead to the development of dilated cardiomyopathy. Experimental autoimmune myocarditis is an animal model which mimics myocarditis in order to allow assessment of the therapeutic effects of different molecules on this disease. We aimed to review the inflammatory and immunological mechanisms involved in the pathogenesis of the myocarditis and finding natural products and phytochemicals with anti-myocarditis activities based on studies of cardiac myosin-induced experimental autoimmune myocarditis in rodents. A number of natural molecules (e.g. apigenin, berberine and quercetin) along with some plant extracts were found to be effective in alleviating experimental autoimmune myocarditis. Upregulation of Th1-type cytokines and elevation of the Th2-type cytokines (IL-4 and IL-10), mitigation of oxidative stress, modulation of mitogen-activated protein kinase signaling pathways and increasing Sarco-endoplasmic reticulum Ca2+-ATPase levels are among the most important anti-myocarditis mechanisms for the retrieved molecules and extracts. Interestingly, there are structural similarities between the anti-EAM compounds, suggesting the presence of similar pharmacophore and enzymatic targets for these molecules. Naturally occurring molecules discussed in the present article are potential anti-myocarditis drugs and future additional animal studies and clinical trials would shed more light on their effectiveness in the treatment of myocarditis and prevention of dilated cardiomyopathy.