Exosomes derived from cardiac telocytes exert positive effects on endothelial cells.
Telocytes are novel cells that have been documented in the interstitium of multiple organs; however, their role in the heart remains unclear. This study aimed to identify cardiac telocytes by their morphological and molecular features and investigate whether their exosomes affect cardiac endothelial cells. To this end, rat cardiac telocytes were cultured and stained with methylene blue, Janus Green B, and MitoTracker green, or with antibodies for established cell surface markers, and examined by microscopy. In addition, telocyte organelles and exosome release were examined by transmission electron microscopy. To investigate exosome functions, we isolated exosomes from telocytes and co-cultured them with endothelial cells in vitro, as well as transfusing them into a rat model of myocardial infarction. We confirmed that cultured telocytes exhibit normal characteristics, including long, thin prolongations with a moniliform appearance, as well as positive expression of c-Kit, CD34, and vimentin. Furthermore, we observed mitochondria throughout the cell body and telopodes, and found that telocytes actively secrete exosomes. Interestingly, endothelial cells cultured with telocyte supernatants or exosomes exhibited increased proliferation, migration, and formation of capillary-like structures, and these effects were attenuated when exosomes were depleted from telocyte supernatants. Finally, treating myocardial infarction-induced rats with telocyte exosomes resulted in decreased cardiac fibrosis, improved cardiac function, and increased angiogenesis. Taken together, our results provide novel insight into cardiac telocytes, suggesting that they communicate with neighboring endothelial cells via exosome secretion and that these exosomes exert potentially beneficially effects.


Promiscuous activities of heterologous enzymes lead to unintended metabolic rerouting in Saccharomyces cerevisiae engineered to assimilate various sugars from renewable biomass.
Understanding the global metabolic network, significantly perturbed upon promiscuous activities of foreign enzymes and different carbon sources, is crucial for systematic optimization of metabolic engineering of yeast Saccharomyces cerevisiae. Here, we studied the effects of promiscuous activities of overexpressed enzymes encoded by foreign genes on rerouting of metabolic fluxes of an engineered yeast capable of assimilating sugars from renewable biomass by profiling intracellular and extracellular metabolites. Unbiased metabolite profiling of the engineered S. cerevisiae strain EJ4 revealed promiscuous enzymatic activities of xylose reductase and xylitol dehydrogenase on galactose and galactitol, respectively, resulting in accumulation of galactitol and tagatose during galactose fermentation. Moreover, during glucose fermentation, a trisaccharide consisting of glucose accumulated outside of the cells probably owing to the promiscuous and transglycosylation activity of β-glucosidase expressed for hydrolyzing cellobiose. Meanwhile, higher accumulation of fatty acids and secondary metabolites was observed during xylose and cellobiose fermentations, respectively. The heterologous enzymes functionally expressed in S. cerevisiae showed promiscuous activities that led to unintended metabolic rerouting in strain EJ4. Such metabolic rerouting could result in a low yield and productivity of a final product due to the formation of unexpected metabolites. Furthermore, the global metabolic network can be significantly regulated by carbon sources, thus yielding different patterns of metabolite production. This metabolomic study can provide useful information for yeast strain improvement and systematic optimization of yeast metabolism to manufacture bio-based products.


One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome.
Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program. The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy. After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without. With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.


Perfusion culture enhanced human endometrial stromal cell growth in alginate-multivalent integrin α5β1 ligand scaffolds.
A method to functionalize alginate by introducing monomeric or self-assembling (tetrameric) fibronectin (FN) domains is described, leading to a functional scaffold, which is used for three dimensional (3D) culture of human endometrial stromal cells (EnSCs). EnSCs encapsulated in the functional alginate were cultured under perfusion using the TissueFlex® platform, a multiple parallel microbioreactor system for 3D cell culture. The effect of the novel scaffold and the effect of perfusion were examined. Cell viability, proliferation, and extracellular matrix (ECM) deposition were determined and the results compared with those obtained with cells encapsulated in non-functionalized alginate, and also those without perfusion. Staining for focal adhesions and actin showed maximal cell adhesion only for alginate-tetrameric FN scaffolds under perfusion, associated with a significant increase in cell number over 7 days culture; in contrast to poor cell adhesion and a decrease in cell number for non-functionalized alginate scaffolds (irrespective of perfused/static culture) and 3D static culture (irrespective of the scaffold). Conjugation of alginate to FN was an absolute requirement to attenuate the loss of cell metabolic activity over 7 days culture. ECM deposition for blank alginate and alginate-monomeric FN was similar, but increased around 2-fold and 3-fold for alginate-tetrameric FN under static and perfusion culture, respectively. It is concluded that the requirement for EnSC engagement with multivalent integrin α5β1 ligands and perfused culture are both essential as a first step toward endometrial tissue engineering.


Tai Chi-based exercise program provided via telerehabilitation compared to home visits in a post-stroke population who have returned home without intensive rehabilitation: study protocol for a randomized, non-inferiority clinical trial.
The incidence of strokes in industrialized nations is on the rise, particularly in the older population. In Canada, a minority of individuals who have had a stroke actually receive intensive rehabilitation because most stroke patients do not have access to services or because their motor recovery was judged adequate to return home. Thus, there is a considerable need to organize home-based rehabilitation services for everyone who has had a stroke. To meet this demand, telerehabilitation, particularly from a service center to the patient's home, is a promising alternative approach that can help improve access to rehabilitation services once patients are discharged home. This non-inferiority study will include patients who have returned home post-stroke without requiring intensive rehabilitation. To be included in the study, participants will: 1) not be referred to an Intensive Functional Rehabilitation Unit, 2) have a Rankin score of 2 or 3, and 3) have a balance problem (Berg Balance Scale score between 46 and 54). Participants will be randomly assigned to either the teletreatment group or the home visits group. Except for the delivery mode, the intervention will be the same for both groups, that is, a personalized Tai Chi-based exercise program conducted by a trained physiotherapist (45-minute session twice a week for eight consecutive weeks). The main objective of this research is to test the non-inferiority of a Tai Chi-based exercise program provided via telerehabilitation compared to the same program provided in person at home in terms of effectiveness for retraining balance in individuals who have had a stroke but do not require intensive functional rehabilitation. The main outcome of this study is balance and mobility measured with the Community Balance and Mobility Scale. Secondary outcomes include physical and psychological capacities related to balance and mobility, participants' quality of life, satisfaction with services received, and cost-effectiveness associated with the provision of both types of services. ClinicalTrials.gov: NCT01848080.


Managing children with chronic myeloid leukaemia (CML): recommendations for the management of CML in children and young people up to the age of 18 years.
Chronic myeloid leukaemia in children and young people is a relatively rare form of leukaemia that shows increased incidence with age and some evidence suggests that the molecular basis differs from that in adults. Significant advances in targeted therapy with the development and use in children of tyrosine kinase inhibitors and the ability to monitor and understand the prognostic significance of minimal residual disease by standardized molecular techniques has shifted the management of this condition from bone marrow transplantation as the main therapeutic modality to individualized treatment for each patient based on achieving specific milestones. The physiological changes occurring during childhood, particularly those affecting growth and development and the long-term use of treatment, pose specific challenges in this age group, which we are only beginning to understand.


Validation of the GRade, Age, Nodes and Tumor (GRANT) score within the Surveillance Epidemiology and End Results (SEER) database: A new tool to predict survival in surgically treated renal cell carcinoma patients.
The purpose of the present study was to validate the new GRade, Age, Nodes and Tumor (GRANT) score for renal cell carcinoma (RCC) prognostication within a large population of patients. Within the Surveillance, Epidemiology, and End Results database, we identified patients with either clear-cell or papillary RCC, who underwent nephrectomy between 2001 and 2015. Harrell's C-Index, calibration plot and decision curve analysis were used to validate the GRANT model using a five-risk group stratification (0 vs. 1 vs. 2 vs. 3 vs. 4 risk factors). The primary endpoint was overall survival (OS) at 60 months. The analyses were repeated according to the histologic subgroup. The overall population included 73217 cases; 60900 with clear-cell RCC and 12317 with papillary histology, respectively. According to a five-risk group stratification, 23985 patients (32.8%) had no risk factor (0), 35019 (47.8%) had only one risk factor (1), 13275 (18.1%) had risk score 2854 (1.2%) had 3 risk factors and 84 (0.1%) of cases had a GRANT score of 4, respectively. At 60 months, OS rates as determined by the GRANT score were respectively 94% (score 0) vs. 86% (score 1) vs. 76% (score 2) vs. 46% (score 3) vs. 16% (score 4). In both histologic subtypes, the GRANT score yielded good calibration and high net benefit. OS C-Index values were 0.677 and 0.650 for clear-cell and papillary RCC at 60 months after surgery, respectively. In conclusion, the GRANT score was validated with a five-risk group stratification in a huge population from the SEER database, offering a further demonstration of its reliability for prognostication in RCC.


Vehiculation of Active Principles as a Way to Create Smart and Biofunctional Textiles.
In some specific fields of application (e.g., cosmetics, pharmacy), textile substrates need to incorporate sensible molecules (active principles) that can be affected if they are sprayed freely on the surface of fabrics. The effect is not controlled and sometimes this application is consequently neglected. Microencapsulation and functionalization using biocompatible vehicles and polymers has recently been demonstrated as an interesting way to avoid these problems. The use of defined structures (polymers) that protect the active principle allows controlled drug delivery and regulation of the dosing in every specific case. Many authors have studied the use of three different methodologies to incorporate active principles into textile substrates, and assessed their quantitative behavior. Citronella oil, as a natural insect repellent, has been vehicularized with two different protective substances; cyclodextrine (CD), which forms complexes with it, and microcapsules of gelatin-arabic gum. The retention capability of the complexes and microcapsules has been assessed using an in vitro experiment. Structural characteristics have been evaluated using thermogravimetric methods and microscopy. The results show very interesting long-term capability of dosing and promising applications for home use and on clothes in environmental conditions with the need to fight against insects. Ethyl hexyl methoxycinnamate (EHMC) and gallic acid (GA) have both been vehicularized using two liposomic-based structures: Internal wool lipids (IWL) and phosphatidylcholine (PC). They were applied on polyamide and cotton substrates and the delivery assessed. The amount of active principle in the different layers of skin was determined in vitro using a Franz-cell diffusion chamber. The results show many new possibilities for application in skin therapeutics. Biofunctional devices with controlled functionality can be built using textile substrates and vehicles. As has been demonstrated, their behavior can be assessed using in vitro methods that make extrapolation to their final applications possible.


[Active and passive immunization in the extremely preterm infant].
A review of the indications, contraindications, ideal timing, immunogenic efficacy and reactogenicity (adverse events) of active and passive immunization for extremely preterm infants. Research in classic textbooks on pediatric infectology and in the electronic databases MEDLINE, Lilacs, PubMed and Akwanmed, using the following health sciences descriptors: premature, very low weight newborn, immunization, active immunization, passive immunization, vaccines, immunoglobulin. The immunization of extremely premature very low birth weight infants is a huge challenge for pediatricians because there is insufficient knowledge about the efficacy of immune responses and undesirable reactions. Possibly for this reason, it is common that such children are found to be behind schedule with their immunizations or to have been incompletely immunized. Notwithstanding the scarcity of publications on the theme, in principal young gestational age and low birth weight should not be considered limiting factors to clinically stable premature newborns being immunized at the same chronological age indicated for full term children. Based on the available evidence it not possible to propose vaccine and immunoglobulin administration practice for extremely premature or very low weight newborn babies that is definitive. With rare exceptions however, such as the BCG vaccine, the tendency is to maintain the same active immunization program as for babies born full term, irrespective of weight or gestational age at birth. Passive immunization merits special attention, having more liberal indications in this group of newborn babies.


Short- and long-term efficacy of intra-articular injections with betamethasone as part of a treat-to-target strategy in early rheumatoid arthritis: impact of joint area, repeated injections, MRI findings, anti-CCP, IgM-RF and CRP.
To investigate the short-term and long-term efficacy of intra-articular betamethasone injections, and the impact of joint area, repeated injections, MRI pathology, anticyclic citrullinated peptide (CCP) and immunoglobulin M rheumatoid factor (IgM-RF) status in patients with early rheumatoid arthritis (RA). During 2 years of follow-up in the CIMESTRA trial, 160 patients received intra-articular betamethasone in up to four swollen joints/visit in combination with disease-modifying antirheumatic drugs. Short-term efficacy was assessed by EULAR good response. Long-term efficacy by Kaplan-Meier plots of the joint injection survival (ie, the time between injection and renewed flare). Potential predictors of joint injection survival were tested. 1373 Unique joints (ankles, elbows, knees, metacarpophalangeal (MCP), metatarsophalangeal, proximal interphalangeal (PIP), shoulders, wrists) were injected during 2 years. 531 Joints received a second injection, and 262 a third. At baseline, the median numbers of injections (dose of betamethasone) was 4 (28 mg), declining to 0 (0 mg) at subsequent visits. At weeks 2, 4 and 6, 50.0%, 58.1% and 61.7% had achieved a EULAR good response. After 1 and 2 years, respectively, 62.3% (95% CI 58.1% to 66.9%) and 55.5% (51.1% to 60.3%) of the joints injected at baseline had not relapsed. All joint areas had good 2-year joint injection survival, longest for the PIP joints: 73.7% (79.4% to 95.3%). 2-Year joint injection survival was higher for first injections: 56.6% (53.7% to 59.8%) than for the second: 43.4% (38.4% to 49.0%) and the third: 31.3% (25.0% to 39.3%). Adverse events were mild and transient. A high MRI synovitis score of MCP joints and anti-CCP-negativity were associated with poorer joint injection survival, whereas IgM-RF and C-reactive protein were not. In early RA, intra-articular injections of betamethasone in small and large peripheral joints resulted in rapid, effective and longlasting inflammatory control. The cumulative dose of betamethasone was low, and the injections were well tolerated.


Corticosterone acts in the nucleus accumbens to enhance dopamine signaling and potentiate reinstatement of cocaine seeking.
Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may "set the stage" for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intra-accumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake₂-mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake₂ inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake₂ transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake.


Intragenic suppression of trafficking-defective KCNH2 channels associated with long QT syndrome.
Mutations in the KCNH2 or human ether-a-go-go-related gene-encoded K(+) channel reduce functional KCNH2 current (I(KCNH2)) to cause long QT syndrome (LQT2) by multiple mechanisms, including defects in intracellular transport (trafficking). Trafficking-deficient, or class 2, LQT2 mutations reduce the Golgi processing and surface membrane expression of KCNH2 channel proteins. Drugs that associate with pore-S6 intracellular drug binding domain of KCNH2 channel proteins to cause high-affinity block of I(KCNH2) also can increase the processing of class 2 LQT2 channel proteins through the secretory pathway. We used a strategy of intragenic suppression to test the hypothesis that amino acid substitutions in the putative drug binding domain at residue Y652 could compensate for protein folding abnormalities caused by class 2 LQT2 mutations. We found that the Y652C substitution, and to lesser extent the Y652S substitution, resulted in intragenic suppression of the class 2 LQT2 G601S phenotype; these substitutions increased Golgi processing of G601S channel proteins. The Y652C substitution also caused intragenic suppression of the class 2 LQT2 V612L and F640V phenotypes but not the LQT2 N470D or F805C phenotypes. These are the first findings to demonstrate that a single amino acid substitution in the putative KCNH2 drug binding domain can cause intragenic suppression of several LQT2 mutations.


Metallic artefact reduction with monoenergetic dual-energy CT: systematic ex vivo evaluation of posterior spinal fusion implants from various vendors and different spine levels.
To evaluate optimal monoenergetic dual-energy computed tomography (DECT) settings for artefact reduction of posterior spinal fusion implants of various vendors and spine levels. Posterior spinal fusion implants of five vendors for cervical, thoracic and lumbar spine were examined ex vivo with single-energy (SE) CT (120 kVp) and DECT (140/100 kVp). Extrapolated monoenergetic DECT images at 64, 69, 88, 105 keV and individually adjusted monoenergy for optimised image quality (OPTkeV) were generated. Two independent radiologists assessed quantitative and qualitative image parameters for each device and spine level. Inter-reader agreements of quantitative and qualitative parameters were high (ICC = 0.81-1.00, κ = 0.54-0.77). HU values of spinal fusion implants were significantly different among vendors (P < 0.001), spine levels (P < 0.01) and among SECT, monoenergetic DECT of 64, 69, 88, 105 keV and OPTkeV (P < 0.01). Image quality was significantly (P < 0.001) different between datasets and improved with higher monoenergies of DECT compared with SECT (V = 0.58, P < 0.001). Artefacts decreased significantly (V = 0.51, P < 0.001) at higher monoenergies. OPTkeV values ranged from 123-141 keV. OPTkeV according to vendor and spine level are presented herein. Monoenergetic DECT provides significantly better image quality and less metallic artefacts from implants than SECT. Use of individual keV values for vendor and spine level is recommended. • Artefacts pose problems for CT following posterior spinal fusion implants. • CT images are interpreted better with monoenergetic extrapolation using dual-energy (DE) CT. • DECT extrapolation improves image quality and reduces metallic artefacts over SECT. • There were considerable differences in monoenergy values among vendors and spine levels. • Use of individualised monoenergy values is indicated for different metallic hardware devices.


PARP-1 hyperactivation and reciprocal elevations in intracellular Ca2+ during ROS-induced nonapoptotic cell death.
The generation of reactive oxygen species (ROS) has been implicated in the pathogenesis of renal ischemia/reperfusion injury, and many other pathological conditions. DNA strand breaks caused by ROS lead to the activation of poly(ADP-ribose)polymerase-1 (PARP-1), the excessive activation of which can result in cell death. We have utilized a model in which 2,3,5-tris(glutathion-S-yl)hydroquinone (TGHQ), a nephrotoxic and nephrocarcinogenic metabolite of hydroquinone, causes ROS-dependent cell death in human renal proximal tubule epithelial cells (HK-2), to further elucidate the role of PARP-1 in ROS-dependent cell death. TGHQ-induced ROS generation, DNA strand breaks, hyperactivation of PARP-1, rapid depletion of nicotinamide adenine dinucleotide (NAD), elevations in intracellular Ca(2+) concentrations, and subsequent nonapoptotic cell death in both a PARP- and Ca(2+)-dependent manner. Thus, inhibition of PARP-1 with PJ34 completely blocked TGHQ-mediated accumulation of poly(ADP-ribose) polymers and NAD consumption, and delayed HK-2 cell death. In contrast, chelation of intracellular Ca(2+) with BAPTA completely abrogated TGHQ-induced cell death. Ca(2+) chelation also attenuated PARP-1 hyperactivation. Conversely, inhibition of PARP-1 modulated TGHQ-mediated changes in Ca(2+) homeostasis. Interestingly, PARP-1 hyperactivation was not accompanied by the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, a process usually associated with PARP-dependent cell death. Thus, pathways coupling PARP-1 hyperactivation to cell death are likely to be context-dependent, and therapeutic strategies designed to target PARP-1 need to recognize such variability. Our studies provide new insights into PARP-1-mediated nonapoptotic cell death, during which PARP-1 hyperactivation and elevations in intracellular Ca(2+) are reciprocally coupled to amplify ROS-induced nonapoptotic cell death.


RTN4/NoGo-receptor binding to BAI adhesion-GPCRs regulates neuronal development.
RTN4-binding proteins were widely studied as "NoGo" receptors, but their physiological interactors and roles remain elusive. Similarly, BAI adhesion-GPCRs were associated with numerous activities, but their ligands and functions remain unclear. Using unbiased approaches, we observed an unexpected convergence: RTN4 receptors are high-affinity ligands for BAI adhesion-GPCRs. A single thrombospondin type 1-repeat (TSR) domain of BAIs binds to the leucine-rich repeat domain of all three RTN4-receptor isoforms with nanomolar affinity. In the 1.65 Å crystal structure of the BAI1/RTN4-receptor complex, C-mannosylation of tryptophan and O-fucosylation of threonine in the BAI TSR-domains creates a RTN4-receptor/BAI interface shaped by unusual glycoconjugates that enables high-affinity interactions. In human neurons, RTN4 receptors regulate dendritic arborization, axonal elongation, and synapse formation by differential binding to glial versus neuronal BAIs, thereby controlling neural network activity. Thus, BAI binding to RTN4/NoGo receptors represents a receptor-ligand axis that, enabled by rare post-translational modifications, controls development of synaptic circuits.


Intradermal immunization with ovalbumin-loaded poly-epsilon-caprolactone microparticles conferred protection in ovalbumin-sensitized allergic mice.
Although immunotherapy has been reported as the only treatment able to revert the T-helper type 2 (Th2) response, its administration has some disadvantages such as the requirement of multiple doses, possible side-effects provoked by conventional adjuvants and the risk of suffering an anaphylactic shock. For these reasons, drug-delivery systems appear to be a promising strategy due to its ability to (i) transport the allergens, (ii) protect them from degradation, (iii) decrease the number of administrations and (iv) act as immuno-adjuvants. The aim of this work was to evaluate the properties of poly-epsilon-caprolactone (PCL) microparticles as adjuvants in immunotherapy using ovalbumin (OVA) as an allergen model. For this purpose, the protection capacity of these microparticles (OVA PCL) against OVA allergy was studied in a murine model. The humoral and cellular-induced immune response generated by OVA encapsulated into PCL microparticles was studied by immunizing BALB/c mice intradermically. Also, OVA-sensitized mice were treated with OVA PCL and OVA adsorbed to aluminium hydroxide (OVA-Alum). Fifteen days after therapy, animals were challenged with OVA and different signs of anaphylactic shock were evaluated. One single shot by an intradermal route with OVA PCL resulted in a Th2-type immune response. In OVA-sensitized mice, treatment with OVA PCL elicited high OVA-specific IgG but low levels of IgE. Furthermore, OVA PCL mice group displayed lower levels of serum histamine and higher survival rate in comparison with the positive control group. The anaphylactic shock suffered by OVA PCL-treated mice was weaker than the one induced in the OVA-Alum group. Hence, the intradermal immunization with OVA PCL microparticles induced hyposensitization in OVA-allergic mice.


Development of on-shore behavior among polar bears (Ursus maritimus) in the southern Beaufort Sea: inherited or learned?
Polar bears (Ursus maritimus) are experiencing rapid and substantial changes to their environment due to global climate change. Polar bears of the southern Beaufort Sea (SB) have historically spent most of the year on the sea ice. However, recent reports from Alaska indicate that the proportion of the SB subpopulation observed on-shore during late summer and early fall has increased. Our objective was to investigate whether this on-shore behavior has developed through genetic inheritance, asocial learning, or through social learning. From 2010 to 2013, genetic data were collected from SB polar bears in the fall via hair snags and remote biopsy darting on-shore and in the spring from captures and remote biopsy darting on the sea ice. Bears were categorized as either on-shore or off-shore individuals based on their presence on-shore during the fall. Levels of genetic relatedness, first-order relatives, mother-offspring pairs, and father-offspring pairs were determined and compared within and between the two categories: on-shore versus off-shore. Results suggested transmission of on-shore behavior through either genetic inheritance or social learning as there was a higher than expected number of first-order relatives exhibiting on-shore behavior. Genetic relatedness and parentage data analyses were in concurrence with this finding, but further revealed mother-offspring social learning as the primary mechanism responsible for the development of on-shore behavior. Recognizing that on-shore behavior among polar bears was predominantly transmitted via social learning from mothers to their offspring has implications for future management and conservation as sea ice continues to decline.


Reversible Band Gap Narrowing of Sn-Based Hybrid Perovskite Single Crystal with Excellent Phase Stability.
An intriguing reversible band gap narrowing behavior of the lead-free hybrid perovskite single crystal DMASnI3 (DMA=CH3 NH2 CH3 + ) from yellow to black is observed without phase transformation. We discuss the transformation mechanism in detail. More interestingly, the transformed samples in black can rapidly self-heal into yellow ones when exposed to deionized water (DI water). Contrary to other hybrid perovskites, DMASnI3 crystals exhibit excellent water phase stability. For example, DMASnI3 was immersed in DI water for 16 h and no decomposition was observed. Inspired by its excellent water phase stability, we demonstrate a potential eco-friendly application of DMASnI3 in photo-catalysis for H2 evolution in DI water. We present the first H2 evolution rate of 0.64 μmol h-1 with good recycling properties for pure DMASnI3 crystals. After the narrowing process, the optical band gap of DMASnI3 can be lowered from 2.48 eV to 1.32 eV. Systematical characterizations are applied to investigate their structures and optoelectronic properties. The reversible band gap narrowing behavior and outstanding electrical properties, such as higher carrier mobility and long carrier lifetime show that DMASnI3 has a great potential for optoelectronic applications.


Risk factors associated with major cerebrovascular complications after intracranial stenting.
There are limited data on the relationship between patient and site characteristics and clinical outcomes after intracranial stenting. We performed a multivariable analysis that correlated patient and site characteristics with the occurrence of the primary endpoint (any stroke or death within 30 days of stenting or stroke in the territory of the stented artery beyond 30 days) in 160 patients enrolled in this stenting registry. All patients presented with an ischemic stroke, TIA, or other cerebral ischemic event (e.g., vertebrobasilar insufficiency) in the territory of a suspected 50-99% stenosis of a major intracranial artery while on antithrombotic therapy. Cerebral angiography confirmed that 99% (158/160) of patients had a 50-99% stenosis. In multivariable analysis, the primary endpoint was associated with posterior circulation stenosis (vs anterior circulation) (hazard ratio [HR] 3.4, 95% confidence interval [CI] 1.2-9.3, p = 0.018), stenting at low enrollment sites (< 10 patients each) (vs high enrollment site) (HR 2.8, 95% CI 1.1-7.6, p = 0.038), < or = 10 days from qualifying event to stenting (vs > or = 10 days) (HR 2.7, 95% CI 1.0-7.8, p = 0.058), and stroke as a qualifying event (vs TIA/other) (HR 3.2, 95% CI 0.9-11.2, p = 0.064). There was no significant difference in the primary endpoint based on age, gender, race, or percent stenosis (50-69% vs 70-99%). Major cerebrovascular complications after intracranial stenting may be associated with posterior circulation stenosis, low volume sites, stenting soon after a qualifying event, and stroke as the qualifying event. These factors will need to be monitored in future trials of intracranial stenting.


The effect of Malaysian cocoa extract on glucose levels and lipid profiles in diabetic rats.
The present study aims to investigate the effect of cocoa extract on serum glucose levels and lipid profiles in streptozotocin-diabetic rats. Cocoa extract (contained 285.6 mg total polyphenol per gram extract) was prepared from fermented and roasted (140 degrees C, 20 min) beans by extracting using 80% ethanol in the ratio of 1-10. The extract of three dosages (1, 2, and 3%) was fed to normal and diabetic rats for a period of 4 weeks. In hyperglycaemic group, cocoa extract (1 and 3%) diets were found to significantly lower (p<0.05) the serum glucose levels compared to the control. Furthermore, supplementation of 1 and 3% cocoa extract had significantly reduced (p<0.05) the level of total cholesterol in diabetic rats. In addition, 1, 2, and 3% cocoa extract diets had significantly lowered (p<0.05) the total triglycerides. Interestingly, this study found that serum HDL-cholesterol had increased significantly (p<0.05) in diabetic rats fed with 2% cocoa extract, while the LDL-cholesterol had decreased significantly (p<0.05) in the 1% treated group. These results indicate that cocoa extract may possess potential hypoglycaemic and hypocholestrolemic effects on serum glucose levels and lipid profiles, respectively. The results also found that the effect of cocoa extract was dose-dependent.


Illness beliefs and psychological outcome in people with Parkinson's disease.
Illness beliefs are important predictors of psychological outcome in people with chronic illness and evidence suggests these could also be significant in furthering our understanding of psychological functioning in people with Parkinson's disease. Illness beliefs are specific, dynamic representations of an illness and cover dimensions such as cause, identity, consequences and controllability. Eighty-one people with Parkinson's disease completed a series of questionnaires to provide demographic, clinical and psychosocial data, which were then used to assess the relative impact of illness beliefs on their psychological functioning. Psychological functioning was assessed by measuring levels of depression, anxiety, stress, positive affect and emotional well-being. Hierarchical block regression indicated that illness beliefs were important independent predictors across some but not all outcomes and the results emphasised the importance of testing new predictors against more established predictors of outcome such as physical functioning and self-esteem. The illness beliefs most important in psychological outcome in people with PD were causal beliefs (particularly in psychosocial causes) and illness coherence (the level of understanding of the illness). The therapeutic potential of psychosocial variables was discussed given that these can be modified during therapy and this change can positively influence psychological outcome.


Developing a set of consensus indicators to support maternity service quality improvement: using Core Outcome Set methodology including a Delphi process.
To develop a core metric set to monitor the quality of maternity care. Delphi process followed by a face-to-face consensus meeting. English maternity units. Three representative expert panels: service designers, providers and users. Maternity care metrics judged important by participants. Participants were asked to complete a two-phase Delphi process, scoring metrics from existing local maternity dashboards. A consensus meeting discussed the results and re-scored the metrics. In all, 125 distinct metrics across six domains were identified from existing dashboards. Following the consensus meeting, 14 metrics met the inclusion criteria for the final core set: smoking rate at booking; rate of birth without intervention; caesarean section delivery rate in Robson group 1 women; caesarean section delivery rate in Robson group 2 women; caesarean section delivery rate in Robson group 5 women; third- and fourth-degree tear rate among women delivering vaginally; rate of postpartum haemorrhage of ≥1500 ml; rate of successful vaginal birth after a single previous caesarean section; smoking rate at delivery; proportion of babies born at term with an Apgar score <7 at 5 minutes; proportion of babies born at term admitted to the neonatal intensive care unit; proportion of babies readmitted to hospital at <30 days of age; breastfeeding initiation rate; and breastfeeding rate at 6-8 weeks. Core outcome set methodology can be used to incorporate the views of key stakeholders in developing a core metric set to monitor the quality of care in maternity units, thus enabling improvement. Achieving consensus on core metrics for monitoring the quality of maternity care.


British Society of Gastroenterology Endoscopy Quality Improvement Programme (BSG EQIP): Implementing new endoscopic techniques and technologies into clinical practice.
Endoscopy has rapidly evolved from a diagnostic modality to a therapeutic tool with the advent of new technologies (medical devices or imaging) and techniques (types of procedures). Although the rapid advancement of technology is welcomed, this can pose its own problems if there is no robust system in place to assess the safety and efficacy of new endoscopic devices or practices or guide its use among clinicians prior to adoption. This is unlike the rigorous process that medical drugs need to go through from preclinical to clinical phases of development, often with controlled trials being conducted prior to integration of a new drug into clinical practice. In this review, we will identify the problems related to implementation of new technologies and techniques as well as propose solutions. We will outline the use of comparative effectiveness studies as a model for assessing new technologies and provide a structured pathway to support clinicians in their endeavour to introduce new devices or procedures in their clinical practice safely. We will also discuss the role of the British Society of Gastroenterology in risk stratifying new techniques and supporting clinicians in setting up national registries, training and business case development. This review will provide a framework for improving the quality and safety of our current practice of implementing new endoscopic technologies and techniques in the National Health Service.


SEROPREVALENCE OF TOXOPLASMA GONDII IN RODENTS FROM VARIOUS LOCATIONS IN PENINSULAR MALAYSIA.
Numerous studies have reported the prevalence of toxoplasmosis among Malaysians and various domestic animals; but there is paucity of information on its prevalence among rodents which could potentially contribute to the transmission of Toxoplasma gondii in both domestic and sylvatic fauna. Five hundred twenty-six rodents were captured from six locations in Malaysia and identified to species. Serum samples were collected from these rodents and tested for T.gondii antibodies using an immunofluorescent antibody test (IFAT). T.gondii antibodies were found in 5.9% (31/526) of the tested samples. Most of the positive antibodies were from commensal rats: Rattus exulans (9/64, 14.0%), Rattus argentiventer (2/8, 25%), Rattus rattus diardii (10/166, 6.0%) and Rattus tiomanicus (6/215, 2.7%). Only two of the forest rats were positive: Maxomys rajah (1/9, 11.1%) and Rattus bowersi (1/12, 8.3%). Eighteen point one percent of ground squirrels (Tupaia glis) tested (2/11) were positive for antibodies. The highest antibodies titer (1:1024) was found in Rattus exulans followed by T.glis (1:256). Sabak Bernam, Selangor had the highest prevalence (10.8%) followed by Baling, Kedah (5.0%) and Bagan Terap, Selangor (4.0%). None of the serum samples of rodents collected from Gua Musang, Kelantan; Jasin, Malacca; or Labis, Johor were positive. Our study reports for the first time the serologic prevalence of T.gondii antibodies among rodents in Peninsular Malaysia. Further studies are needed to confirm T.gondii infection among wild rodents, such as a bioassay, to assess their potential role in transmission of the parasite.


AgBioData consortium recommendations for sustainable genomics and genetics databases for agriculture.
The future of agricultural research depends on data. The sheer volume of agricultural biological data being produced today makes excellent data management essential. Governmental agencies, publishers and science funders require data management plans for publicly funded research. Furthermore, the value of data increases exponentially when they are properly stored, described, integrated and shared, so that they can be easily utilized in future analyses. AgBioData (https://www.agbiodata.org) is a consortium of people working at agricultural biological databases, data archives and knowledgbases who strive to identify common issues in database development, curation and management, with the goal of creating database products that are more Findable, Accessible, Interoperable and Reusable. We strive to promote authentic, detailed, accurate and explicit communication between all parties involved in scientific data. As a step toward this goal, we present the current state of biocuration, ontologies, metadata and persistence, database platforms, programmatic (machine) access to data, communication and sustainability with regard to data curation. Each section describes challenges and opportunities for these topics, along with recommendations and best practices.


Parental feeding practices and the relationship with parents in female adolescents and young adults with eating disorders: A case control study.
Perceived parental influence on diet in early adolescence in the context of the parental relationship had previously not been studied in a clinical sample. The aim of this study was to investigate a possible association between eating disorders and characteristics of the relationship with parents and the parental feeding practices in early adolescence. 21 female adolescents and young adults with an eating disorder (ED)-bulimia nervosa or anorexia nervosa-and 22 females without eating disorder (healthy control; HC), aged between 16 and 26, were assessed via self-report questionnaires for problematic eating behaviour, relationship with parents, perceptions of parent's feeding practices at the age of 10-13 years and personality. Statistical evaluation was performed by means of group comparisons, effect sizes, regression analyses and mediator analyses. Adolescent and young adult females with ED reported more fears/overprotection and rejection/neglect by their mothers and less self-responsibility in terms of eating behaviour during adolescence than did the HC. The relationship with the fathers did not differ significantly. Females who perceived more cohesion, rejection/neglect and fears/overprotection by the mother were more likely to suffer from an ED. Rejection/neglect by both parents were associated with less self-acceptance of the young females with even stronger effect sizes for the fathers than the mothers. Harm prevention in the young females was a partial mediator between fears/overprotection and the drive for thinness. The parental relationship is partly reflected in the self-acceptance and self-responsibility in eating of the adolescent and young females, both of them are particularly affected in EDs. Stressors in the parent-child relationship should be targeted in treatment of eating disorders. Nutritional counselling for parents might be useful in early adolescence.


An effective general purpose approach for automated biomedical document classification.
Automated document classification can be a valuable tool for biomedical tasks that involve large amounts of text. However, in biomedicine, documents that have the desired properties are often rare, and special methods are usually required to address this issue. We propose and evaluate a method of classifying biomedical text documents, optimizing for utility when misclassification costs are highly asymmetric between the positive and negative classes. The method uses chi-square feature selection and several iterations of cost proportionate rejection sampling followed by application of a support vector machine (SVM), combining the resulting classifier results with voting. It is straightforward, fast, and achieves competitive performance on a set of standardized biomedical text classification evaluation tasks. The method is a good general purpose approach for classifying biomedical text.


Renal renin activity is associated with alterations of the renin gene in recombinant inbred rat strains.
1. A structural alteration within the first intron of the renin gene in spontaneously hypertensive rats was demonstrated to co-segregate with blood pressure in some sets of F2 hybrids or recombinant inbred strains. There is no evidence as to whether restriction fragment length polymorphism of the renin gene is associated with any of the changes in the renin tissue level. For this reason we have determined renal renin activity in spontaneously hypertensive, Wistar-Kyoto and Brown Norway rats as well as in 22 recombinant inbred strains derived from F2 hybrids of spontaneously hypertensive and Brown Norway rats. 2. At the age of 4 months significantly lower renal renin activity was observed in spontaneously hypertensive rats than in both normotensive rat strains, Wistar-Kyoto and Brown Norway. The presence of the spontaneously hypertensive rat allele in recombinant inbred strains was associated with a substantially lower renal renin activity as compared with recombinant inbred strains bearing the Brown Norway rat allele. There was no relationship between renal renin activity and the polymorphism in either the angiotensinogen gene or the angiotensin-converting enzyme gene. 3. There was a borderline correlation between blood pressure and renal renin activity in recombinant inbred strains. Nevertheless, additional comparisons within recombinant inbred strains bearing the spontaneously hypertensive rat allele of the renin gene failed to reveal any significant relationship between blood pressure level and renal renin activity. 4. Our data suggest that the restriction fragment length polymorphism marking the renin gene of the spontaneously hypertensive rat is accompanied by an alteration in the renin-angiotensin system at the renal level.(ABSTRACT TRUNCATED AT 250 WORDS)


Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.
Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1(gt/gt) mice, the overall survival rates of the Mcph1(gt/gt) animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.


Mechanisms of Abrupt Loss of Virus Control in a Cohort of Previous HIV Controllers.
Elite and viremic HIV controllers are able to control their HIV infection and maintain undetectable or low-level viremia in the absence of antiretroviral treatment. Despite extensive studies, the immune factors responsible for such exclusive control remain poorly defined. We identified a cohort of 14 HIV controllers that suffered an abrupt loss of HIV control (LoC) to investigate possible mechanisms and virological and immunological events related to the sudden loss of control. The in-depth analysis of these subjects involved the study of cell tropism of circulating virus, evidence for HIV superinfection, cellular immune responses to HIV, as well as an examination of viral adaptation to host immunity by Gag sequencing. Our data demonstrate that a poor capacity of T cells to mediate in vitro viral suppression, even in the context of protective HLA alleles, predicts a loss of viral control. In addition, the data suggest that inefficient viral control may be explained by an increase of CD8 T-cell activation and exhaustion before LoC. Furthermore, we detected a switch from C5- to X4-tropic viruses in 4 individuals after loss of control, suggesting that tropism shift might also contribute to disease progression in HIV controllers. The significantly reduced inhibition of in vitro viral replication and increased expression of activation and exhaustion markers preceding the abrupt loss of viral control may help identify untreated HIV controllers that are at risk of losing control and may offer a useful tool for monitoring individuals during treatment interruption phases in therapeutic vaccine trials.IMPORTANCE A few individuals can control HIV infection without the need for antiretroviral treatment and are referred to as HIV controllers. We have studied HIV controllers who suddenly lose this ability and present with high in vivo viral replication and decays in their CD4+ T-cell counts to identify potential immune and virological factors that were responsible for initial virus control. We identify in vitro-determined reductions in the ability of CD8 T cells to suppress viral control and the presence of PD-1-expressing CD8+ T cells with a naive immune phenotype as potential predictors of in vivo loss of virus control. The findings could be important for the clinical management of HIV controller individuals, and it may offer an important tool to anticipate viral rebound in individuals in clinical studies that include combination antiretroviral therapy (cART) treatment interruptions and which, if not treated quickly, could pose a significant risk to the trial participants.


Small-angle neutron scattering study of a dense microemulsion system formed with an ionic liquid.
Mixtures of water, octane and 1-octanol with 1-tetradecyl-3-methylimidazolium chloride (C14MIM·Cl), often referred to as a surface active ionic liquid (SAIL), form water-in-oil microemulsions that have potential application as extraction media for various metal ions. Here, we present a structural study by small-angle neutron scattering (SANS) of dense microemulsions formed by surfactant-rich mixtures of these four compounds to understand how the SAIL can be used to tune the structures and properties of the microemulsions. The SANS experiments revealed that the microemulsions formed are composed of two phases, a water-in-oil microemulsion and a bicontinuous microemulsion, which becomes the dominant phase at high surfactant concentration. In this concentration regime, the surfactant film becomes more rigid, having a higher bending modulus that results from the parallel stacking of the imidazolium ring of the SAIL. At lower surfactant concentrations, the molecular packing of the SAIL does not change with the water content of the microemulsion. The results presented here correlate well with previously observed changes in the interaction between the IL cation and metal ions (Y. Tong, L. Han and Y. Yang, Ind. Eng. Chem. Res., 2012, 51, 16438-16443), while the capacity of the microemulsion system for water remains high enough for using the system as an extraction medium.


Multi-sensor integration for an assessment of underwater radiated noise from common vessels in San Francisco Bay.
There is growing evidence that smaller vessels not required to broadcast data via the Automatic Identification System (AIS) contribute significant noise to urbanized coastal areas. The Marine Monitor (M2), a vessel tracking system that integrates AIS data with data collected via marine radar and high-definition camera, was employed to track all vessel types (regardless of AIS data availability) in a region of San Francisco Bay (SFB) where high-speed ferry, recreational, and commercial shipping traffic are common. Using a co-located hydrophone, source levels (SL) associated with 565 unique vessel passages were calculated and resultant cumulative daily sound exposure levels across the study area were modeled. Despite large ships primarily having the highest SLs, ferries and motorized recreational craft contributed noise to the largest area in two frequency bands of interest. The M2 provided data without the need for an on-site observer and enabled a systematic analysis of all relevant vessel types which showed that non-AIS vessels should not be excluded from consideration, especially in a highly urbanized estuary like SFB. This research provides an assessment of underwater radiated noise from all common vessel types in SFB suitable for informing habitat quality and threat evaluation for local cetacean species.


Developing the Diagnostic Adherence to Medication Scale (the DAMS) for use in clinical practice.
There is a need for an adherence measure, to monitor adherence services in clinical practice, which can distinguish between different types of non-adherence and measure changes over time. In order to be inclusive of all patients it needs to be able to be administered to both patients and carers and to be suitable for patients taking multiple medications for a range of clinical conditions. A systematic review found that no adherence measure met all these criteria. We therefore wished to develop a theory based adherence scale (the DAMS) and establish its content, face and preliminary construct validity in a primary care population. The DAMS (consisting of 6 questions) was developed from theory by a multidisciplinary team and the questions were initially tested in small patient populations. Further to this, patients were recruited when attending a General Practice and interviewed using the DAMS and two other validated self-reported adherence measures, the Morisky-8 and Lu questionnaires. A semi-structured interview was used to explore acceptability and reasons for differences in responses between the DAMS and the other measures. Descriptive data were generated and Spearman rank correlation tests were used to identify associations between the DAMS and the other adherence measures. One hundred patients completed the DAMS in an average of 1 minute 28 seconds and reported finding it straightforward to complete. An adherence score could not be calculated for the 4(4%) patients only taking 'when required' medication. Thirty six(37.5%) of the remaining patients reported some non-adherence. Adherence ratings of the DAMS were significantly associated with levels of self reported adherence on all other measures Spearman Rho 0.348-0.719, (p < 0.01). Differences in trends could generally be explained by qualitative data. The DAMS has been developed for routine monitoring of adherence in clinical practice. It was acceptable to patients taking single or multiple medication and valid when tested against other adherence measures. However, 'when required' medication needs to be excluded. Further tests of the DAMS against objective measures such as MEMS are in progress and reliability needs to be established. Further investigation of the carers' version of the DAMS is required.


Psychiatric complications of treatment with corticosteroids: review with case report.
Corticosteroids are widely used in modern medicine but can result in troubling psychiatric side-effects. Physicians and other medical professionals should be aware of the potential for these side-effects, possible means of prevention, and efficacious treatments. Herein, we review adult case report data published during the past quarter-century on adverse corticosteroid-induced psychiatric effects, and present a case of corticosteroid-induced psychotic depression. PubMed and PsychLit databases were searched using the terms 'corticosteroids', 'steroids', and the generic names of corticosteroid medications with terms for psychiatric symptoms or syndromes, including psychosis, mania, hypomania, depression, apathy, anxiety, panic, depersonalization, delirium, confusion, hallucinations, delusions, paranoia, cognitive impairment and dementia. Fifty-five cases and a number of clinical trials investigating the incidence and treatment of these psychiatric symptoms and syndromes were identified. Data on incidence, drug dose, risk factors, course of illness and treatment (when present) were tabulated. We conclude that the cumulative data indicate that psychiatric complications of corticosteroid treatment are not rare and range from clinically significant anxiety and insomnia, to severe mood and psychotic disorders, delirium and dementia. While tapering or discontinuation of the corticosteroid treatment may remedy these adverse side-effects, psychotropic medications are often required because of the medical necessity of the corticosteroid or the severity of the psychiatric symptom. Further studies are needed to better understand the deleterious psychiatric effects associated with corticosteroids.


On-site infiltration of road runoff using pervious pavements with subjacent infiltration trenches as source control strategy.
The focus in this work was on subsoil infiltration of stormwater from parking lots. With regard to operation, reduced infiltration performance due to clogging and pollutants in seepage, which may contribute to contaminate groundwater, are of interest. The experimental investigation covered a pervious pavement with a subjacent infiltration trench draining an impervious area of 2 ha. In order to consider seasonal effects on the infiltration performance, the hydraulic conductivity was measured tri-monthly during monitoring with a mobile sprinkling unit. To assess natural deposits jointing, road bed, gravel of infiltration trenches and subsoil were analysed prior to commencement of monitoring for heavy metals, polycyclic aromatic and mineral oil type hydrocarbons. Furthermore, from 22 storm events, water samples of rainfall, surface runoff, seepage and ground water were analysed with regard to the above mentioned pollutants. The study showed that the material used for the joints had a major impact on the initial as well as the final infiltration rates. Due to its poor hydraulic conductivity, limestone gravel should not be used as jointing. Furthermore, it is recommended that materials for the infiltration facilities are ensured free of any contaminants prior to construction. Polycyclic aromatic and mineral oil type hydrocarbons were, with the exception of surface runoff, below detection limits. Heavy metal concentrations of groundwater were with the exception of lead (because of high background concentrations), below the permissible limits.


Performance of an exhaled nitric oxide and carbon dioxide sensor using quantum cascade laser-based integrated cavity output spectroscopy.
Exhaled nitric oxide (NO) is an important biomarker in asthma and other respiratory disorders. The optical performance of a NOCO(2) sensor employing integrated cavity output spectroscopy (ICOS) with a quantum cascade laser operating at 5.22 microm capable of real-time NO and CO(2) measurements in a single breath cycle is reported. A NO noise-equivalent concentration of 0.4 ppb within a 1-sec integration time is achieved. The off-axis ICOS sensor performance is compared to a chemiluminescent NO analyzer and a nondispersive infrared (NDIR) CO(2) absorption capnograph. Differences between the gas analyzers are assessed by the Bland-Altman method to estimate the expected variability between the gas sensors. The off-axis ICOS sensor measurements are in good agreement with the data acquired with the two commercial gas analyzers. This work demonstrates the performance characteristics and merits of mid-infrared spectroscopy for exhaled breath analysis.


Nanoscale studies link amyloid maturity with polyglutamine diseases onset.
The presence of expanded poly-glutamine (polyQ) repeats in proteins is directly linked to the pathogenesis of several neurodegenerative diseases, including Huntington's disease. However, the molecular and structural basis underlying the increased toxicity of aggregates formed by proteins containing expanded polyQ repeats remain poorly understood, in part due to the size and morphological heterogeneity of the aggregates they form in vitro. To address this knowledge gap and technical limitations, we investigated the structural, mechanical and morphological properties of fibrillar aggregates at the single molecule and nanometer scale using the first exon of the Huntingtin protein as a model system (Exon1). Our findings demonstrate a direct correlation of the morphological and mechanical properties of Exon1 aggregates with their structural organization at the single aggregate and nanometric scale and provide novel insights into the molecular and structural basis of Huntingtin Exon1 aggregation and toxicity.


Surfactant protein D is expressed and modulates inflammatory responses in human coronary artery smooth muscle cells.
Surfactant protein D (SP-D) is a constituent of the innate immune system that plays a role in the host defense against lung pathogens and in modulating inflammatory responses. While SP-D has been detected in extrapulmonary tissues, little is known about its expression and function in the vasculature. Immunostaining of human coronary artery tissue sections demonstrated immunoreactive SP-D protein in smooth muscle cells (SMCs) and endothelial cells. SP-D was also detected in isolated human coronary artery SMCs (HCASMCs) by PCR and immunoblot analysis. Treatment of HCASMCs with endotoxin (LPS) stimulated the release of IL-8, a proinflammatory cytokine. This release was inhibited >70% by recombinant SP-D. Overexpression of SP-D by adenoviral-mediated gene transfer in HCASMCs inhibited both LPS- and TNF-alpha-induced IL-8 release. Overexpression of SP-D also enhanced uptake of Chlamydia pneumoniae elementary bodies into HCASMCs while attenuating IL-8 production induced by bacterial exposure. Both LPS and TNF-alpha increased SP-D mRNA levels by five- to eightfold in HCASMCs, suggesting that inflammatory mediators upregulate the expression of SP-D. In conclusion, SP-D is expressed in human coronary arteries and functions as an anti-inflammatory protein in HCASMCs. SP-D may also participate in the host defense against pathogens that invade the vascular wall.


Randomised trials relevant to mental health conducted in low and middle-income countries: protocol for a survey of studies published in 1991, 1995 and 2000 and assessment of their relevance.
A substantial proportion of the psychiatric burden of disease falls on the world's poorest nations. Despite this, relatively little is known about the quality and content of clinical research undertaken in these countries, or the relevance of the interventions evaluated and specifically that of randomised trials. This project aims to survey the content, quality and accessibility of a sample of trials relevant to mental health conducted within low and middle-income countries; to compare these with studies conducted in high-income countries; and to assess their relevance for the needs of low and middle-income countries. An extensive search for all trials, or possible trials, published in 1991, 1995 and 2000 with participants in low and middle-income countries has already been conducted. Studies evaluating prevention or treatment of a mental health problem within these three years will be identified and further searches conducted to assess completeness of the initial search. Data on study quality and characteristics will be extracted from each report. Accessibility will be estimated based on whether each citation is available on MEDLINE. Trials relevant to schizophrenia will be compared with a random sample of schizophrenia trials from high-income countries in the same years. Topics covered by the trials will be compared with the estimated burden of disease. Trials and systematic reviews of trials are the gold standard of evaluation of care and increasingly provide the basis for recommendations to clinicians, to providers of care and to policy makers. Results from this study will present the first assessment of the scope, quality and accessibility of mental health trials in low and middle-income countries.


Southern analysis of the 230-kD bullous pemphigoid antigen gene in normal humans, animals, and patients with junctional epidermolysis bullosa.
To begin to characterize the 230-kD bullous pemphigoid antigen (BPA) gene, we performed Southern analysis on genomic DNA with probes derived from 7 kb of cDNA that spans most of the coding region of this hemidesmosomal plaque protein. When hybridized to a 1-kb fragment of this BPA cDNA, normal human genomic DNA digested with EcoRI, BamHI, PstI, HindIII, or EcoRV showed only a single band, which was unique for each enzyme, indicating a single human gene for BPA. To determine if a related gene exists in animals, we used probes covering the full 7 kb of cDNA for Southern analysis of genomic DNA from various vertebrates. A related gene was detected in other mammals (monkey, cow, dog, rabbit, mouse, and rat) but not in chicken, frog, or fish. Under these same hybridization conditions a probe for human beta-actin could detect an actin gene in all these species. Furthermore, immunofluorescence showed that an antibody raised against portions of the 230-kD BPA bound to the epidermal basement membrane of mammals but not that of a bird or amphibian. Finally, because most patients with junctional epidermolysis bullosa (JEB) have defective hemidesmosomes in ultrastructure, and probably function, we analyzed genomic DNA from these patients. No restriction fragment length polymorphisms (RFLP) were detected when the DNA from 11 normals and 8 JEB patients (representing 16 possible defective genes) was digested with BamHI, EcoRI, or PstI and hybridized to any part of the cDNA. These findings indicate that 1) there is a single BPA gene in humans; 2) a closely related gene exists in other mammals but not birds, amphibia, or fish; and 3) gross abnormalities of the BPA gene are not characteristic of JEB patients.


Primary production of the biosphere: integrating terrestrial and oceanic components
Integrating conceptually similar models of the growth of marine and terrestrial primary producers yielded an estimated global net primary production (NPP) of 104.9 petagrams of carbon per year, with roughly equal contributions from land and oceans. Approaches based on satellite indices of absorbed solar radiation indicate marked heterogeneity in NPP for both land and oceans, reflecting the influence of physical and ecological processes. The spatial and temporal distributions of ocean NPP are consistent with primary limitation by light, nutrients, and temperature. On land, water limitation imposes additional constraints. On land and ocean, progressive changes in NPP can result in altered carbon storage, although contrasts in mechanisms of carbon storage and rates of organic matter turnover result in a range of relations between carbon storage and changes in NPP.


Vitamin C-induced decomposition of lipid hydroperoxides to endogenous genotoxins.
Epidemiological data suggest that dietary antioxidants play a protective role against cancer. This has led to the proposal that dietary supplementation with antioxidants such as vitamin C (vit C) may be useful in disease prevention. However, vit C has proved to be ineffective in cancer chemoprevention studies. In addition, concerns have been raised over potentially deleterious transition metal ion-mediated pro-oxidant effects. We have now determined that vit C induces lipid hydroperoxide decomposition to the DNA-reactive bifunctional electrophiles 4-oxo-2-nonenal, 4,5-epoxy-2(E)-decenal, and 4-hydroxy-2-nonenal. The compound 4,5-Epoxy-2(E)-decenal is a precursor of etheno-2'-deoxyadenosine, a highly mutagenic lesion found in human DNA. Vitamin C-mediated formation of genotoxins from lipid hydroperoxides in the absence of transition metal ions could help explain its lack of efficacy as a cancer chemoprevention agent.


Chin on Chest Deformity Caused by Upper Cervical Kyphosis Associated With Ankylosing Spondylitis: A Case Report.
Chin on chest deformity caused by upper cervical kyphosis associated with ankylosing spondylitis is rare. A 66-year-old woman presented at our institute with chief complaints of difficulty in horizontal gaze and opening her mouth. Cervical radiographs showed a C0-2 angle of 1° on flexion and 7° on extension, and her chin-brow vertical angle was 49°. We planned fixation surgery at C0-5 posteriorly to prevent the progression of kyphosis, with slight correction of the kyphosis at C0-2. The correction was performed by pushing down the over lordotically contoured titanium rods connected to an occipital plate onto the C3-5 lateral mass screws, just like cantilever technique. No palpable cracking or loss of resistance was noticed during the correction. However, intraoperative radiographs revealed apparent anterior separation of the vertebral bodies between C3 and C4. Postoperative computed tomography images at the C3/4 level suggested hemorrhage from the fracture site. Tracheostomy was performed because of massive edema around the pharynx. To secure solid bone fusion, staged surgery to extend the fusion to T3 and to graft an additional iliac bone was performed. Fortunately, the C2-7 angle was corrected to 40°, and her chin-brow vertical angle was restored to 17° without any catastrophic complications. Although the patient finally obtained an ideal sagittal alignment, the surgeon should be aware that the technique had a higher perioperative risk for iatrogenic fracture, resulting in neurological and vascular injuries.


Limited Therapeutic Time Windows of Mild-to-Moderate Hypothermia in a Focal Ischemia Model in Rat.
Although many studies have shown the great potential of induced hypothermia in stroke treatment, we recognize that there are limitations to the protective effects of hypothermia even in the laboratory. Here, we review our experiments on the protective effects of mild-to-moderate hypothermia in rats. Focal ischemia was induced by bilateral common carotid artery (CCA) occlusion for 1 to 2 hours combined with permanent or transient middle cerebral artery (MCA) occlusion. We compared the effects of mild (33°C) and moderate (30°C) hypothermia, evaluated therapeutic time windows, and studied the underlying mechanisms. On review, our findings revealed that the protective effects of induced mild hypothermia (33°C) were limited, and the therapeutic time window of even moderate hypothermia (30°C) was very short in our specific models, although this limitation might be due to the relatively brief periods of hypothermia used. In addition, we found that hypothermia reduced brain injury by preserving Akt activity, PTEN phosphorylation and εPKC activity, while inhibiting ROS production, and δPKC activity.


Toxicity of the flame-retardant BDE-49 on brain mitochondria and neuronal progenitor striatal cells enhanced by a PTEN-deficient background.
Polybrominated diphenyl ethers (PBDEs) represent an important group of flame retardants extensively used, tonnage of which in the environment has been steadily increasing over the past 25 years. PBDEs or metabolites can induce neurotoxicity and mitochondrial dysfunction (MD) through a variety of mechanisms. Recently, PBDEs with < 5 Br substitutions (i.e., 2,2',4,4'-tetrabromodiphenyl ether [BDE-47] and 2,2',4,5'-tetrabromodiphenyl ether [BDE-49]) have gained interest because of their high bioaccumulation. In particular, congeners such as BDE-49 arise as one of the most biologically active, with concentrations typically lower than those observed for BDE-47 in biological tissues; however, its potential to cause MD at biologically relevant concentrations is unknown. To this end, the effect of BDE-49 was studied in brain mitochondria and neuronal progenitor striatal cells (NPC). BDE-49 uncoupled mitochondria at concentrations < 0.1 nM, whereas at > 1 nM, it inhibited the electron transport at Complex V (mixed type inhibition; IC(50) = 6 nM) and Complex IV (noncompetitive inhibition; IC(50) = 40 nM). These concentrations are easily achieved in plasma concentrations considering that BDE-49 (this study, 400-fold) and other PBDEs accumulate 1-3 orders of magnitude in the cells, particularly in mitochondria and microsomes. Similar effects were observed in NPC and exacerbated with PTEN (negative modulator of the PI3K/Akt pathway) deficiency, background associated with autism-like behavior, schizophrenia, and epilepsy. PBDE-mediated MD per se or enhanced by a background that confers susceptibility to this exposure may have profound implications in the energy balance of brain.


Aryl Hydrocarbon Receptor is Essential in the Control of Lung Club Cell Homeostasis.
Club cells play an important role in maintaining lung homeostasis and aryl hydrocarbon receptor (AhR) is known to be important in xenobiotic metabolism, but its role in regulating club cells is currently unknown. To this end, mice with club cell-specific AhR deficiency were generated and evaluated in a model of antigen (ovalbumin, OVA)-induced airway inflammation for the number of infiltrating inflammatory cells, the levels of cytokines and CC10 and Notch signaling by standard methods. After OVA sensitization and challenge, Scgb1a1-Cre; Ahrflox/flox mice showed aggravated levels of pulmonary inflammation with increased levels of inflammatory cells and cytokines 1 day after challenge as compared to those seen in their littermate controls, but in contrast to the littermate controls, no significant change in the levels of CC10 and SP-D was noted in Scgb1a1-Cre; Ahrflox/flox mice. Surprisingly, 7 days after the challenge, while, as expected, wild-type mice recovered from acute inflammation, significantly increased lymphocytic infiltration was noted in Scgb1a1-Cre; Ahrflox/flox mice, suggesting their defective mechanism of recovery. Mechanistically, this was due, in part, to the decreased Notch1 signaling and expression of its downstream gene, HES5, while AhR was shown to positively regulate Notch1 expression via its transactivating activity targeting the xenobiotic response element in the promoter region of Notch1 gene. Under the condition of pulmonary inflammation, AhR is critical in controlling lung club cell homeostasis via targeting Notch1 signaling and the generation of anti-inflammatory mediators.


Serum osteoprotegerin and renal function in the general population: the Tromsø Study.
Serum osteoprotegerin (OPG) is elevated in patients with chronic kidney disease (CKD) and increases with decreasing renal function. However, there are limited data regarding the association between OPG and renal function in the general population. The aim of the present study was to explore the relation between serum OPG and renal function in subjects recruited from the general population. We conducted a cross-sectional study with 6689 participants recruited from the general population in Tromsø, Norway. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equations. OPG was modelled both as a continuous and categorical variable. General linear models and linear regression with adjustment for possible confounders were used to study the association between OPG and eGFR. Analyses were stratified by the median age, as serum OPG and age displayed a significant interaction on eGFR. In participants ≤62.2 years with normal renal function (eGFR ≥90 mL/min/1.73 m2) eGFR increased by 0.35 mL/min/1.73 m2 (95% CI 0.13-0.56) per 1 standard deviation (SD) increase in serum OPG after multiple adjustment. In participants older than the median age with impaired renal function (eGFR <90 mL/min/1.73 m2), eGFR decreased by 1.54 (95% CI -2.06 to -1.01) per 1 SD increase in serum OPG. OPG was associated with an increased eGFR in younger subjects with normal renal function and with a decreased eGFR in older subjects with reduced renal function. Our findings imply that the association between OPG and eGFR varies with age and renal function.


In-plane graphene/boron-nitride heterostructures as an efficient metal-free electrocatalyst for the oxygen reduction reaction.
Exploiting metal-free catalysts for the oxygen reduction reaction (ORR) and understanding their catalytic mechanisms are vital for the development of fuel cells (FCs). Our study has demonstrated that in-plane heterostructures of graphene and boron nitride (G/BN) can serve as an efficient metal-free catalyst for the ORR, in which the C-N interfaces of G/BN heterostructures act as reactive sites. The formation of water at the heterointerface is both energetically and kinetically favorable via a four-electron pathway. Moreover, the water formed can be easily released from the heterointerface, and the catalytically active sites can be regenerated for the next cycle. Since G/BN heterostructures with controlled domain sizes have been successfully synthesized in recent reports (e.g. Nat. Nanotechnol., 2013, 8, 119), our results highlight the great potential of such heterostructures as a promising metal-free catalyst for the ORR in FCs.


Modelling population dynamics and seasonal movement to assess and predict the burden of melioidosis.
Melioidosis is an infectious disease that is transmitted mainly through contact with contaminated soil or water, and exhibits marked seasonality in most settings, including Southeast Asia. In this study, we used mathematical modelling to examine the impacts of such demographic changes on melioidosis incidence, and to predict the disease burden in a developing country such as Thailand. A melioidosis infection model was constructed which included demographic data, diabetes mellitus (DM) prevalence, and melioidosis disease processes. The model was fitted to reported melioidosis incidence in Thailand by age, sex, and geographical area, between 2008 and 2015, using a Bayesian Markov Chain Monte Carlo (MCMC) approach. The model was then used to predict the disease burden and future trends of melioidosis incidence in Thailand. Our model predicted two-fold higher incidence rates of melioidosis compared with national surveillance data from 2015. The estimated incidence rates among males were two-fold greater than those in females. Furthermore, the melioidosis incidence rates in the Northeast region population, and among the transient population, were more than double compared to the non-Northeast region population. The highest incidence rates occurred in males aged 45-59 years old for all regions. The average incidence rate of melioidosis between 2005 and 2035 was predicted to be 11.42 to 12.78 per 100,000 population per year, with a slightly increasing trend. Overall, it was estimated that about half of all cases of melioidosis were symptomatic. In addition, the model suggested a greater susceptibility to melioidosis in diabetic compared with non-diabetic individuals. The increasing trend of melioidosis incidence rates was significantly higher among working-age Northeast and transient populations, males aged ≥45 years old, and diabetic individuals. Targeted intervention strategies, such as health education and awareness raising initiatives, should be implemented on high-risk groups, such as those living in the Northeast region, and the seasonally transient population.


A characteristic Mls-1a response precedes Mls-1a anergy in vivo.
T cells expressing V beta 6 variable gene segments of the T cell receptor undergo blast formation and divide in mice after injection of lymphoid cells bearing minor lymphocyte-stimulating (Mls)-1a gene products. This in vivo Mls-1a response resembles in vitro Mls-1a stimulation; it is dose dependent, not MHC-class II haplotype restricted, but requires expression of functional IE gene products. The in vivo Mls-1a response is followed by a complete and specific in vivo Mls-1a anergy and a partial in vitro Mls-1a anergy. The measurement of a Mls-1a response in vivo and of the establishment of in vivo anergy to it provides a convenient method to assay Mls-1a reactivity of T cells in vivo on a cell-by-cell basis in terms of cell surface phenotype, size, and mitotic activity.


Diverse impacts of the rs58542926 E167K variant in TM6SF2 on viral and metabolic liver disease phenotypes.
A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The roles of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD and viral load in chronic viral hepatitis, as well as its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3260 subjects with viral and nonviral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (P = 0.02) but not different in cohorts with CHC (n = 2023) and chronic hepatitis B (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases and with reduced hepatic TM6SF2 and microsomal triglyceride transfer protein expression. Interestingly, the substitution was associated with reduced CHC viral load but increased hepatitis B virus DNA. The rs58542926 T allele had no effect on inflammation, impacted ≥F2 fibrosis in CHC and NAFLD assessed cross-sectionally (odds ratio = 1.39, 95% confidence interval 1.04-1.87, and odds ratio = 1.62, 95% confidence interval 1.03-2.52, respectively; P < 0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. The TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and microsomal triglyceride transfer protein expression and differentially impacts CHC and chronic hepatitis B viral load, while effects on fibrosis are marginal. (Hepatology 2016;64:34-46).


Vitamin D3 and brain development.
Evidence for the presence of the vitamin D receptor in brain implies this vitamin may have some function in this organ. This study investigates whether vitamin D(3) acts during brain development. We demonstrate that rats born to vitamin D(3)-deficient mothers had profound alterations in the brain at birth. The cortex was longer but not wider, the lateral ventricles were enlarged, the cortex was proportionally thinner and there was more cell proliferation throughout the brain. There were reductions in brain content of nerve growth factor and glial cell line-derived neurotrophic factor and reduced expression of p75(NTR), the low-affinity neurotrophin receptor. Our findings would suggest that low maternal vitamin D(3) has important ramifications for the developing brain.


Functionally distinct laminin receptors mediate cell adhesion and spreading: the requirement for surface galactosyltransferase in cell spreading.
The molecular mechanisms underlying cell attachment and subsequent cell spreading on laminin are shown to be distinct form one another. Cell spreading is dependent upon the binding of cell surface galactosyltransferase (GalTase) to laminin oligosaccharides, while initial cell attachment to laminin occurs independent of GalTase activity. Anti-GalTase IgG, as well as the GalTase modifier protein, alpha-lactalbumin, both block GalTase activity and inhibited B16-F10 melanoma cell spreading on laminin, but not initial attachment. On the other hand, the addition of UDP galactose, which increases the catalytic turnover of GalTase, slightly increased cell spreading. None of these reagents had any effect on cell spreading on fibronectin. When GalTase substrates within laminin were either blocked by affinity-purified GalTase or eliminated by prior galactosylation, cell attachment appeared normal, but subsequent cell spreading was totally inhibited. The laminin substrate for GalTase was identified as N-linked oligosaccharides primarily on the A chain, and to a lesser extent on B chains. That N-linked oligosaccharides are necessary for cell spreading was shown by the inability of cells to spread on laminin surfaces pretreated with N-glycanase, even though cell attachment was normal. Cell surface GalTase was distinguished from other reported laminin binding proteins, most notably the 68-kD receptor, since they were differentially eluted from laminin affinity columns. These data show that surface GalTase does not participate during initial cell adhesion to laminin, but mediates subsequent cell spreading by binding to its appropriate N-linked oligosaccharide substrate. These results also emphasize that some of laminin's biological properties can be attributed to its oligosaccharide residues.


Morphological, immunological, and biochemical analyses of chicken spleen cells transformed in vitro by reticuloendotheliosis virus strain T.
Reticuloendotheliosis virus strain T (REV-T) is a highly oncogenic avian retrovirus which causes a rapid neoplastic disease of the lymphoreticular system. We derived six cell lines (1-3, 1-5, 2-10, 2-14, 2-16, and 2-20) from chicken spleen cells infected with REV-T. These cells can produce both the REV-T and its associated reticuloendotheliosis helper virus, REV-A. Histochemical analyses of these cells indicate that, while they are not stained by benzidine, peroxidase, beta-glucuronidase or acid alpha-naphthyl acetate esterase, they contain a high proportion (95%) of cells positive for acid phosphatase. Light and electron microscopic studies of these cells also revealed morphologies of lymphoblasts or activated lymphocytes with irregular nuclei and dispersed chromatin. Immunochemical analyses indicate that essentially all (90 to 100%) of the cells contain the surface marker Ia, but no cytoplasmic immunoglobulin M and immunoglobulin G could be detected by immunofluorescence staining. Results also show that some of these cell lines contain a low level of terminal transferase (0.02 to 0.17 unit/10(9) cells), and a proportion (3 to 35%) of these cells can be stained by an antiserum directed against chicken bursa cells. These results are consistent with the conclusion that the cells transformed by the highly oncogenic REV-T are lymphoid in nature. In addition, at least some of these cell clones may contain features characteristic of activated B-lymphocytes. Analysis of these cell clones indicates that some cell lines contain an adherent and nonadherent population with some differences in morphologies. In addition, electron microscopic examination revealed that, while the non-adherent cells are actively producing type C viruses, type C viruses are either absent or very rare in the adherent cell populations. These results support the conclusion that some of these cell lines are heterogeneous and contain subpopulations of cells with differences in their ability to produce viruses.


Evaluation of the Efficacy and Safety of DA-9601 versus Its New Formulation, DA-5204, in Patients with Gastritis: Phase III, Randomized, Double-Blind, Non-Inferiority Study.
This study compared the efficacy of DA-9601 (Dong-A ST Co., Seoul, Korea) and its new formulation, DA-5204 (Dong-A ST Co.), for treating erosive gastritis. This phase III, randomized, multicenter, double-blind, non-inferiority trial randomly assigned 434 patients with endoscopically proven gastric mucosal erosions into two groups: DA-9601 3 times daily or DA-5,204 twice daily for 2 weeks. The final analysis included 421 patients (DA-5204, 209; DA-9601, 212). The primary endpoint (rate of effective gastric erosion healing) and secondary endpoints (cure rate of endoscopic erosion and gastrointestinal [GI] symptom relief) were assessed using endoscopy after the treatment. Drug-related adverse events (AEs), including GI symptoms, were also compared. At week 2, gastric healing rates with DA-5204 and DA-9601 were 42.1% (88/209) and 42.5% (90/212), respectively. The difference between the groups was -0.4% (95% confidence interval, -9.8% to 9.1%), which was above the non-inferiority margin of -14%. The cure rate of gastric erosion in both groups was 37.3%. The improvement rates of GI symptoms with DA-5204 and DA-9601 were 40.4% and 40.8%, respectively. There were no statistically significant differences between the two groups in both secondary endpoints. AEs were reported in 18 (8.4%) patients in the DA-5204 group and 19 (8.8%) in the DA-9601 group. Rates of AE were not different between the two groups. No serious AE or adverse drug reaction (ADR) occurred. These results demonstrate the non-inferiority of DA-5204 compared to DA-9601. DA-5204 is as effective as DA-9601 in the treatment of erosive gastritis. Registered randomized clinical trial at ClinicalTrials.gov (NCT02282670).


The whole world will be able to see us: determining the characteristics of a culturally appropriate bed net among mestizo communities of the Peruvian Amazon.
The Peruvian Ministry of Health has distributed insecticide-treated nets (ITNs) in the country's Amazon region since 1999. Net use is nearly universal among mestizo communities in this area, but residents traditionally use non-impregnated muslin nets. We evaluated the cultural acceptability of Ministry ITNs using qualitative methods. Our results show that nets serve various functions for users: protection against insect bites, warmth, privacy, and a sense of security for young children. Because the Ministry-distributed ITNs could not fulfill these functions as well as traditional nets, many recipients disliked or rejected the ITNs they received. Also, because the ITN fabric stains rapidly, recipients washed their nets frequently rather than waiting 6 months as recommended. We propose a two-pronged approach that balances user and health system expectations of bed nets and that should lead to more widespread and effective ITN use in the study communities.


[Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration rate in chronic kidney disease patients].
The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely used strategy to assess chronic kidney disease. Nonetheless, for the individual patient the true GFR can be underestimated with the risk of diagnosing a more elevated CKD stage. This novel CKD-EPI equation would improve accuracy and precision of estimations, and several authors recommend this new equation replace the former. In our country there is only a limited registration of these comparisons performed on a large number of patients. Therefore, our aim was to develop a comparison in a wide cohort of patients. The concordance between both equations to assign the GFR stages was determined by using the MDRD formula as a reference. The mean difference of GFR obtained with both equations as well as the Bland-Altman analysis were calculated. A cohort of 9319 individuals, of whom 67% were females, aged 58 ± 20 years, with serum creatinine values of 1.6 ± 1.03 mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61 ml/min/1.73 m2 larger than MDRD (p: NS). For CKD stages 2 and 3A the mean estimated GFR difference was 6.95 ± 4.76 and 3.21 ± 3.31, while the concordance was 81 and 74% respectively. The percentage of patients with GFR < 60 ml/min/1.73 m2, decreased from 76.3% with the former equation to 70.1% with the latter. The novel equation CKD-EPI reduces the number of patients with GFR values lower than 60 ml/min/1.73 m2 and consequently assigns a higher GFR stage to a considerable quantity of individuals.


Stepwise graded refractive-index profiles for design of a narrow-bandpass filter.
A combination of stepwise graded refractive-index profiles and a cavity structure is used for designing narrow-bandpass filters of TiO(2)/SiO(2) multilayer films upon BK7 glass substrates. Symmetrical profiles of stepwise graded refractive indices result in high transmittance of passbands for the designed filters. The bandwidth of the narrow-bandpass filter is controlled by adjustment of parameters such as the thickness and the number of layers in the multilayer stack. This design is proposed as a new and simple method for coating synthesis of optical filters.


Effect of Low-intensity Exercise on Physical and Cognitive Health in Older Adults: a Systematic Review.
It is well known that physical exercise is important to promote physical and cognitive health in older population. However, inconsistent research findings were shown regarding exercise intensity, particularly on whether low-intensity exercise (1.5 metabolic equivalent tasks (METs) to 3.0 METs) can improve physical and cognitive health of older adults. This systematic review aimed to fill this research gap. The objective of this study is to conduct a systematic review of the effectiveness of low-intensity exercise interventions on physical and cognitive health of older adults. Published research was identified in various databases including CINAHL, MEDLINE, PEDro, PubMed, Science Direct, SPORTDiscus, and Web of Science. Research studies published from January 01, 1994 to February 01, 2015 were selected for examination. Studies were included if they were published in an academic peer-reviewed journal, published in English, conducted as randomized controlled trial (RCT) or quasi-experimental studies with appropriate comparison groups, targeted participants aged 65 or above, and prescribed with low-intensity exercise in at least one study arm. Two reviewers independently extracted the data (study, design, participants, intervention, and results) and assessed the quality of the selected studies. Fifteen studies met the inclusion criteria. Quality index ranged from 15 to 18 mean = 18.3 with a full score of 28, indicating a moderate quality. Most of the outcomes reported in these studied were lower limb muscle strength (n = 9), balancing (n = 7), flexibility (n = 4), and depressive symptoms (n = 3). Out of the 15 selected studies, 11 reported improvement in flexibility, balancing, lower limb muscle strength, or depressive symptoms by low-intensity exercises. The current literature suggests the effectiveness of low-intensity exercise on improved physical and cognitive health for older adults. It may be a desired intensity level in promoting health among older adults with better compliance, lower risk of injuries, and long-term sustainability.