Embolization of rolandic cortex arteriovenous malformations.
To evaluate the safety and efficacy of preradiosurgical and presurgical embolization of arteriovenous malformations (AVMs) involving the rolandic cortex. Seventeen consecutive patients with rolandic AVMs seen during a 31-month period (December 1994-July 1997) were evaluated. All patients underwent superselective sodium amobarbital testing to determine any changes in the results of the neurological examinations before undergoing embolization. In 16 of 17 patients (94.1%), somatosensory evoked potentials augmented physical examinations. Patients were embolized with N-butyl cyanoacrylate (Histoacryl; B. Braun, Melsungen, Germany) and iophendylate (Ethiodol; Savage Labs, Melville, NY). Rigid control of the mean arterial pressure (65-75 mm Hg) was maintained in all patients for 24 to 48 hours after embolization. Twenty-three embolization sessions were performed in 17 patients (mean, 1.5 sessions/patient), and a total of 40 feeding arteries were embolized. Two patients were unable to undergo embolization because of positive results of the amobarbital testing despite repeated attempts to reposition a microcatheter in the AVM circulation. In one case, somatosensory evoked potentials and the results of the physical examination were both positive; in the other case, only the somatosensory evoked potentials were used (in a pediatric patient under general anesthesia). All patients with AVMs that were embolized experienced a significant size reduction of their lesions (range, 20-95%; mean, 63%). There were no permanent complications. Four procedures (10% of the procedures, 23% of the patients) resulted in minor transient neurological deficits, with patients' conditions returning to baseline. Thirteen patients subsequently underwent radiosurgery, three underwent surgical resection, and one underwent combined surgery and radiosurgery. Complete obliteration of the lesions has been achieved in four patients to date (three who underwent surgery and one who underwent radiosurgery), with the remainder undergoing further follow-up. When properly evaluated before treatment, rolandic AVMs can be embolized with a high success rate (measured by completed embolization and size reduction) and a low complication rate.


Evidence for the involvement of the kainate receptor subunit GluR6 (GRIK2) in mediating behavioral displays related to behavioral symptoms of mania.
The glutamate receptor 6 (GluR6 or GRIK2, one of the kainate receptors) gene resides in a genetic linkage region (6q21) associated with bipolar disorder (BPD), but its function in affective regulation is unknown. Compared with wild-type (WT) and GluR5 knockout (KO) mice, GluR6 KO mice were more active in multiple tests and super responsive to amphetamine. In a battery of specific tests, GluR6 KO mice also exhibited less anxious or more risk-taking type behavior and less despair-type manifestations, and they also had more aggressive displays. Chronic treatment with lithium, a classic antimanic mood stabilizer, reduced hyperactivity, aggressive displays and some risk-taking type behavior in GluR6 KO mice. Hippocampal and prefrontal cortical membrane levels of GluR5 and KA-2 receptors were decreased in GluR6 KO mice, and chronic lithium treatment did not affect these decreases. The membrane levels of other glutamatergic receptors were not significantly altered by GluR6 ablation or chronic lithium treatment. Together, these biochemical and behavioral results suggest a unique role for GluR6 in controlling abnormalities related to the behavioral symptoms of mania, such as hyperactivity or psychomotor agitation, aggressiveness, driven or increased goal-directed pursuits, risk taking and supersensitivity to psychostimulants. Whether GluR6 perturbation is involved in the mood elevation or thought disturbance of mania and the cyclicity of BPD are unknown. The molecular mechanism underlying the behavioral effects of lithium in GluR6 KO mice remains to be elucidated.


RNA silencing-suppressor function of Turnip crinkle virus coat protein cannot be attributed to its interaction with the Arabidopsis protein TIP.
The interaction of the coat protein (CP) of Turnip crinkle virus (TCV) with a host protein, TCV-interacting protein (TIP), from Arabidopsis thaliana has been reported previously. This interaction correlates with the ability of TCV CP to elicit the resistance response that is mediated by the resistance gene HRT in Arabidopsis ecotype Di-17. It has also been established that TCV CP is a suppressor of RNA silencing, a process by which the host plant targets viral RNA for degradation. These results have led to the speculation that TIP might be a component of the RNA-silencing pathway and that TCV CP suppresses RNA silencing through its interaction with TIP. In the current report, a number of TCV CP mutants have been investigated for their ability to suppress RNA silencing. These mutants include single amino acid substitution mutants that are known to have lost their ability to interact with TIP, as well as deletion mutants of TCV CP that are of different sizes and from different regions of the protein. Results showed that each of the single amino acid substitution mutants tested retained high levels of RNA silencing-suppressor activity. In addition, a mutant containing a 5 aa deletion in the region that is known to be critical for TIP interaction retained the ability to suppress RNA silencing significantly. Larger deletions in all regions of TCV CP abolished silencing-suppressor activity. It can be concluded from these results that the RNA silencing-suppressor activity of TCV CP cannot be attributed to its ability to interact directly with TIP.


Interdisciplinary medical, nursing, and administrator education in practice: the Johns Hopkins experience.
Reforming graduate medical, nursing and health administrators' education to include the core competencies of interdisciplinary teamwork and quality improvement (QI) techniques is a key strategy to improve quality in hospital settings. Practicing clinicians are best positioned in these settings to understand systems issues and craft potential solutions. The authors describe how, in ten months during 2004 and 2005 the school of medicine, the school of nursing, and an administrative residency program, all at Johns Hopkins University, implemented and evaluated the Achieving Competency Today II Program (ACT II), a structured and interdisciplinary approach to learning QI that was piloted at various sites around the United States. Six teams of learners participated, each consisting of a medical, nursing, and administrative resident. The importance of interdisciplinary participation in planning QI projects, the value of the patient's perspective on systems issues, and the value of a system's perspective in crafting solutions to issues all proved to be valuable lessons. Challenges were encountered throughout the program, such as (1) participants' difficulties in balancing competing academic, personal and clinical responsibilities, (2) difficulties in achieving the intended goals of a broad curriculum, (3) barriers to openly discussing interdisciplinary team process and dynamics, and (4) the need to develop faculty expertise in systems thinking and QI. In spite of these challenges steps have been identified to further enhance and develop interdisciplinary education within this academic setting.


Missed breast cancers at US-guided core needle biopsy: how to reduce them.
Ultrasonographically (US) guided core needle biopsy is currently recognized as a reliable alternative to surgical biopsy for the histopathologic diagnosis of breast lesions. However, despite advances in biopsy devices and techniques, false-negative diagnoses are unavoidable and may delay the diagnosis and treatment of breast cancer. The most common reasons for false-negative diagnosis are (a) technical or sampling errors, (b) failure to recognize or act on radiologic-histologic discordance, and (c) lack of imaging follow-up after a benign biopsy result. Technical difficulties (eg, poor lesion or needle visualization, deeply located lesions, dense fibrotic tissue) cause inaccurate sampling but can be reduced by using modified standard techniques. Radiologic-histologic correlation is also of critical importance in US-guided core needle biopsy. Radiologic-histologic discordance occurs when the histologic results do not provide a sufficient explanation for the imaging features and indicates that the lesion may not have been sampled adequately, so that repeat biopsy is warranted. Appropriate follow-up imaging is invaluable; even patients with concordant benign findings after US-guided core needle biopsy are directed to undergo follow-up imaging because there may be delays in the recognition of false-negative findings. Optimization of technique, radiologic-histologic correlation, and postbiopsy follow-up protocols are recommended to reduce the occurrence of false-negative diagnosis at US-guided core needle biopsy performed by radiologists.


[A video-aided minilaparocholecystectomy].
The main objective is to prospectively evaluate the therapeutic efficacy of minilaparocholecystectomy combined with videolaparoscopic view in cases of complicated gallstones where VLC was risky. We carried out minilaparotomic video-aided cholecystectomy on 110 patients (32 males and 78 females) with preoperative diagnosis of intraabdominal adhesions or biliary severe inflammation. No significant intra or postoperative complications was reported and in all cases pain was never greater than that reported after VLC. In all these cases the anesthetists reported an easier intra-operative management of the vital parameters than with VLC procedures. Minilaparocholecystectomy appears a type of alternative procedure able to combine mini-invasiveness with as low a number as possible of intra- and post-operative complications, in cases where VLC have risk. No significant postoperative pain was reported, and in any case pain was never greater than that reported after VLC. Recovery times were similar to those after VLC; patients were able to return to their normal social and working life within a mean 3 days. The procedure carried out by us is a low-cost one: it does not require disposable instruments From the esthetic viewpoint, video-aided minicholecystectomy minimal scars in our cases, wound ranged from 4 to 6 cm. in length. In patients in whom VLC have risks, video-aided minilaparocholecystectomy represents an easy-to-perform and low-cost alternative. VMC can also be proposed as a procedure of choice in cases of complicated gallstones instead of the traditional open cholecystectomy technique.


Vitamin C: effects of exercise and requirements with training.
Ascorbic acid or vitamin C is involved in a number of biochemical pathways that are important to exercise metabolism and the health of exercising individuals. This review reports the results of studies investigating the requirement for vitamin C with exercise on the basis of dietary vitamin C intakes, the response to supplementation and alterations in plasma, serum, and leukocyte ascorbic acid concentration following both acute exercise and regular training. The possible physiological significance of changes in ascorbic acid with exercise is also addressed. Exercise generally causes a transient increase in circulating ascorbic acid in the hours following exercise, but a decline below pre-exercise levels occurs in the days after prolonged exercise. These changes could be associated with increased exercise-induced oxidative stress. On the basis of alterations in the concentration of ascorbic acid within the blood, it remains unclear if regular exercise increases the metabolism of vitamin C. However, the similar dietary intakes and responses to supplementation between athletes and nonathletes suggest that regular exercise does not increase the requirement for vitamin C in athletes. Two novel hypotheses are put forward to explain recent findings of attenuated levels of cortisol postexercise following supplementation with high doses of vitamin C.


Caffeic acid improves locomotor activity and lessens inflammatory burden in a mouse model of rotenone-induced nigral neurodegeneration: Relevance to Parkinson's disease therapy.
Caffeic acid phenethyl ester is found in honey bee propolis. It has immunomodulatory, anti-inflammatory and anti-cancer properties. Rotenone is a pesticide commonly used for inducing experimental Parkinson's disease (PD) due to complex I inhibition and microglia activating properties. The current study examined neuroprotective effect of caffeic acid against rotenone-induced neurodegeneration in groups of seven mice. Mice received protective doses of caffeic acid (2.5, 5 or 10 mg/kg) daily and nine injections of rotenone (1 mg kg, subcutaneously) - every 48 h. Behavioral evaluation of motor function was done by a battery of tests including open-field test, cylinder test, pole test and rotarod test; all these tests showed motor impairment. Assay of striatal dopamine highlighted a significant decrease and increases in inflammatory markers. In addition, histopathological assessment of substantia nigra neurons demonstrated low immunostaining for tyrosine hydroxylase (TH) in rotenone treated mice. PCR analysis highlighted upregulation for genes encoding CD11b (a microglia surface antigen), cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor-κB (NFκB). Treatment with caffeic acid (5 or 10 mg/kg) amended most of rotenone-induced motor deficits, lessened microglia expression and inflammatory mediators and improved the nigral TH immunostaining. These results confirmed the anti-inflammatory activity of caffeic acid and highlighted its neuroprotective activity against rotenone-induced neurodegeneration in mice.


Influence of chronic amphetamine treatment and acute withdrawal on serotonin synthesis and clearance mechanisms in the rat ventral hippocampus.
Amphetamine withdrawal in both humans and rats is associated with increased anxiety states, which are thought to contribute to drug relapse. Serotonin in the ventral hippocampus mediates affective behaviors, and reduced serotonin levels in this region are observed in rat models of high anxiety, including during withdrawal from chronic amphetamine. This goal of this study was to understand the mechanisms by which reduced ventral hippocampus serotonergic neurotransmission occurs during amphetamine withdrawal. Serotonin synthesis (assessed by accumulation of serotonin precursor as a measure of the capacity of in vivo tryptophan hydroxylase activity), expression of serotonergic transporters, and in vivo serotonergic clearance using in vivo microdialysis were assessed in the ventral hippocampus in adult male Sprague Dawley rats at 24 h withdrawal from chronic amphetamine. Overall, results showed that diminished extracellular serotonin at 24 h withdrawal from chronic amphetamine was not accompanied by a change in capacity for serotonin synthesis (in vivo tryptophan hydroxylase activity), or serotonin transporter expression or function in the ventral hippocampus, but instead was associated with increased expression and function of organic cation transporters (low-affinity, high-capacity serotonin transporters). These findings suggest that 24 h withdrawal from chronic amphetamine reduces the availability of extracellular serotonin in the ventral hippocampus by increasing organic cation transporter-mediated serotonin clearance, which may represent a future pharmacological target for reversing anxiety states during drug withdrawal.


Improved Visualization of Cartilage Canals Using Quantitative Susceptibility Mapping.
Cartilage canal vessels are critical to the normal function of epiphyseal (growth) cartilage and damage to these vessels is demonstrated or suspected in several important developmental orthopaedic diseases. High-resolution, three-dimensional (3-D) visualization of cartilage canals has recently been demonstrated using susceptibility weighted imaging (SWI). In the present study, a quantitative susceptibility mapping (QSM) approach is evaluated for 3-D visualization of the cartilage canals. It is hypothesized that QSM post-processing improves visualization of the cartilage canals by resolving artifacts present in the standard SWI post-processing while retaining sensitivity to the cartilage canals. Ex vivo distal femoral specimens from 3- and 8-week-old piglets and a 1-month-old human cadaver were scanned at 9.4 T with a 3-D gradient recalled echo sequence suitable for SWI and QSM post-processing. The human specimen and the stifle joint of a live, 3-week-old piglet also were scanned at 7.0 T. Datasets were processed using the standard SWI method and truncated k-space division QSM approach. To compare the post-processing methods, minimum/maximum intensity projections and 3-D reconstructions of the processed datasets were generated and evaluated. Cartilage canals were successfully visualized using both SWI and QSM approaches. The artifactual splitting of the cartilage canals that occurs due to the dipolar phase, which was present in the SWI post-processed data, was eliminated by the QSM approach. Thus, orientation-independent visualization and better localization of the cartilage canals was achieved with the QSM approach. Combination of GRE with a mask based on QSM data further improved visualization. Improved and artifact-free 3-D visualization of the cartilage canals was demonstrated by QSM processing of the data, especially by utilizing susceptibility data as an enhancing mask. Utilizing tissue-inherent contrast, this method allows noninvasive assessment of the vasculature in the epiphyseal cartilage in the developing skeleton and potentially increases the opportunity to diagnose disease of this tissue in the preclinical stages, when treatment likely will have increased efficacy.


Coupling of dispersal and aggression facilitates the rapid range expansion of a passerine bird.
Behaviors can facilitate colonization of a novel environment, but the mechanisms underlying this process are poorly understood. On one hand, behavioral flexibility allows for an immediate response of colonizers to novel environments, which is critical to population establishment and persistence. On the other hand, integrated sets of behaviors that display limited flexibility can enhance invasion success by coupling behaviors with dispersal strategies that are especially important during natural range expansions. Direct observations of colonization events are required to determine the mechanisms underlying changes in behavior associated with colonization, but such observations are rare. Here, we studied changes in aggression on a large temporal and spatial scale across populations of two sister taxa of bluebirds (Sialia) to show that coupling of aggression and dispersal strongly facilitated the range expansion of western bluebirds across the northwestern United States over the last 30 years. We show that biased dispersal of highly aggressive males to the invasion front allowed western bluebirds to displace less aggressive mountain bluebirds. However, once mountain bluebirds were excluded, aggression of western bluebirds decreased rapidly across consecutive generations in concordance with local selection on highly heritable aggressive behavior. Further, the observed adaptive microevolution of aggression was accelerated by the link between dispersal propensity and aggression. Importantly, our results show that behavioral changes among populations were not caused by behavioral flexibility and instead strongly implicate adaptive integration of dispersal and aggression in facilitating the ongoing and rapid reciprocal range change of these species in North America.


Study of a Swiss dopa-responsive dystonia family with a deletion in GCH1: redefining DYT14 as DYT5.
To report the study of a multigenerational Swiss family with dopa-responsive dystonia (DRD). Clinical investigation was made of available family members, including historical and chart reviews. Subject examinations were video recorded. Genetic analysis included a genome-wide linkage study with microsatellite markers (STR), GTP cyclohydrolase I (GCH1) gene sequencing, and dosage analysis. We evaluated 32 individuals, of whom 6 were clinically diagnosed with DRD, with childhood-onset progressive foot dystonia, later generalizing, followed by parkinsonism in the two older patients. The response to levodopa was very good. Two additional patients had late onset dopa-responsive parkinsonism. Three other subjects had DRD symptoms on historical grounds. We found suggestive linkage to the previously reported DYT14 locus, which excluded GCH1. However, further study with more stringent criteria for disease status attribution showed linkage to a larger region, which included GCH1. No mutation was found in GCH1 by gene sequencing but dosage methods identified a novel heterozygous deletion of exons 3 to 6 of GCH1. The mutation was found in seven subjects. One of the patients with dystonia represented a phenocopy. This study rules out the previously reported DYT14 locus as a cause of disease, as a novel multiexonic deletion was identified in GCH1. This work highlights the necessity of an accurate clinical diagnosis in linkage studies as well as the need for appropriate allele frequencies, penetrance, and phenocopy estimates. Comprehensive sequencing and dosage analysis of known genes is recommended prior to genome-wide linkage analysis.


Mechano-active tissue engineering of vascular smooth muscle using pulsatile perfusion bioreactors and elastic PLCL scaffolds.
Blood vessels are subjected in vivo to mechanical forces in a form of radial distention, encompassing cyclic mechanical strain due to the pulsatile nature of blood flow. Vascular smooth muscle (VSM) tissues engineered in vitro with a conventional tissue engineering technique may not be functional, because vascular smooth muscle cells (VSMCs) cultured in vitro typically revert from a contractile phenotype to a synthetic phenotype. In this study, we hypothesized that pulsatile strain and shear stress stimulate VSM tissue development and induce VSMCs to retain the differentiated phenotype in VSM engineering in vitro. To test the hypothesis, rabbit aortic smooth muscle cells (SMCs) were seeded onto rubber-like elastic, three-dimensional PLCL [poly(lactide-co-caprolactone), 50:50] scaffolds and subjected to pulsatile strain and shear stress by culturing them in pulsatile perfusion bioreactors for up to 8 weeks. As control experiments, VSMCs were cultured on PLCL scaffolds statically. The pulsatile strain and shear stress enhanced the VSMCs proliferation and collagen production. In addition, a significant cell alignment in a direction radial to the distending direction was observed in VSM tissues exposed to radial distention, which is similar to that of native VSM tissues in vivo, whereas VSMs in VSM tissues engineered in the static condition randomly aligned. Importantly, the expression of SM alpha-actin, a differentiated phenotype of SMCs, was upregulated by 2.5-fold in VSM tissues engineered under the mechano-active condition, compared to VSM tissues engineered in the static condition. This study demonstrates that tissue engineering of VSM tissues in vitro by using pulsatile perfusion bioreactors and elastic PLCL scaffolds leads to the enhancement of tissue development and the retention of differentiated cell phenotype.


Ratiometric fluorescence probe for hydrazine vapor detection and biological imaging.
Hydrazine (N2H4) has been widely applied in most of the chemical industry; however, it is now believed that it can cause serious damage to protein and nucleic acid upon ingestion. Herein we introduced a specially designed molecular probe 1, with an electron deficient lactone group as a specially designed reactive site and a naphthalimide fluorophore that is easily modified owing to lactone involvement. The free probe 1 exhibited blue fluorescence in neutral buffer owing to the low favorability of ICT (intramolecular charge transfer), while the specially designed lactone group could potentially undergo a ring-opening reaction with hydrazine, resulting in a favoured ICT effect and bathochromically shifted (125 nm) fluorescence response. The ratiometric fluorescence signal enabled quantitative determination of hydrazine using probe 1 in complex applications. Besides, probe 1 features a rapid signal response time (within 5 min) and low detection limit (36 nM) for hydrazine. Utilizing these excellent properties, probe 1 was further applied in hydrazine vapor detection and bio-imaging. Conceptually, we now present a new approach for the detection of hydrazine, and the enhanced performances of probe 1 will promote its applications in living systems and the environment.


Efficacy and safety of inhaled anaesthetic for postoperative sedation during mechanical ventilation in adult cardiac surgery patients: a systematic review and meta-analysis.
The aim was to evaluate the efficacy and safety of volatile anaesthetic for postoperative sedation in adult cardiac surgery patients through a systematic review and meta-analysis. We retrieved randomized controlled trials from MEDLINE, EMBASE, CENTRAL, Web of Science, clinical trials registries, conference proceedings, and reference lists of included articles. Independent reviewers extracted data, including patient characteristics, type of intraoperative anaesthesia, inhaled anaesthetic used, comparator sedation, and outcomes of interest, using pre-piloted forms. We assessed risk of bias using the Cochrane Tool and evaluated the strength of the evidence using the GRADE approach. Eight studies enrolling 610 patients were included. Seven had a high and one a low risk of bias. The times to extubation after intensive care unit (ICU) admission and sedation discontinuation were, respectively, 76 [95% confidence interval (CI) -150 to - 2, I2=79%] and 74 min (95% CI - 126 to - 23, I2=96%) less in patients who were sedated using volatile anaesthetic. There was no difference in ICU or hospital length of stay. Patients who received volatile anaesthetic sedation had troponin concentrations that were 0.71 ng ml-1 (95% CI 0.23-1.2) lower than control patients. Reporting on other outcomes was varied and not suitable for meta-analysis. Volatile anaesthetic sedation may be associated with a shorter time to extubation after cardiac surgery but no change in ICU or hospital length of stay. It is associated with a significantly lower postoperative troponin concentration, but the impact of this on adverse cardiovascular outcomes is uncertain. Blinded randomized trials using intention-to-treat analysis are required. PROSPERO registry number: 2016:CRD42016033874. Available from http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42016033874.


Self-assembly of designed coiled coil peptides studied by small-angle X-ray scattering and analytical ultracentrifugation.
α-Helical coiled coil structures, which are noncovalently associated heptad repeat peptide sequences, are ubiquitous in nature. Similar amphipathic repeat sequences have also been found in helix-containing proteins and have played a central role in de novo design of proteins. In addition, they are promising tools for the construction of nanomaterials. Small-angle X-ray scattering (SAXS) has emerged as a new biophysical technique for elucidation of protein topology. Here, we describe a systematic study of the self-assembly of a small ensemble of coiled coil sequences using SAXS and analytical ultracentrifugation (AUC), which was correlated with molecular dynamics simulations. Our results show that even minor sequence changes have an effect on the folding topology and the self-assembly and that these differences can be observed by a combination of AUC, SAXS, and circular dichroism spectroscopy. A small difference in these methods was observed, as SAXS for one peptide and revealed the presence of a population of longer aggregates, which was not observed by AUC.


Autonomic mechanisms in the heart rate response to coughing.
To differentiate between the possible reflex and mechanical components in the heart rate response to cough, eight healthy subjects performed a standardized cough test before and after pharmacological autonomic blockade; to test the clinical usefulness of the cough manoeuvre two groups of diabetic patients (without and with autonomic neuropathy) were compared with a group of age-matched normal subjects. Because of the use of abdominal and expiratory muscles during cough, the cardioacceleratory response was compared with that induced by an intense contraction of the arm muscles (handgrip). The cardioacceleratory response was completely abolished by atropine while propranolol failed to affect it. The diabetic patients with autonomic neuropathy showed a response similar to that after cholinergic blockade. The response was similar to that induced by muscular contraction for 4 s, after which it differed showing a continued cardioacceleration. The patterns of recovery were not different. The cough-induced cardioacceleration is essentially reflex in nature and under cholinergic control; initially the mechanism may be partially related to the intense contraction of abdominal and expiratory muscles; later, the arterial hypotension related to the cough may contribute to the more sustained shortening of the R-R interval. The cough test may be useful for the evaluation of cardiac parasympathetic integrity.


The prevalence of computer and Internet addiction among pupils.
Media have an influence on the human psyche similar to the addictive actions of psychoactive substances or gambling. Computer overuse is claimed to be a cause of psychiatric disturbances such as computer and Internet addiction. It has not yet been recognized as a disease, but it evokes increasing controversy and results in mental disorders commonly defined as computer and Internet addiction. This study was based on a diagnostic survey in which 120 subjects participated. The participants were pupils of three kinds of schools: primary, middle, and secondary school (high school). Information for this study was obtained from a questionnaire prepared by the authors as well as the State-Trait Anxiety Inventory (STAI) and the Psychological Inventory of Aggression Syndrome (IPSA-II). he results confirmed that every fourth pupil was addicted to the Internet. Internet addiction was very common among the youngest users of computers and the Internet, especially those who had no brothers and sisters or came from families with some kind of problems. Moreover, more frequent use of the computer and the Internet was connected with higher levels of aggression and anxiety. Because computer and Internet addiction already constitute a real danger, it is worth considering preventive activities to treat this phenomenon. It is also necessary to make the youth and their parents aware of the dangers of uncontrolled Internet use and pay attention to behavior connected with Internet addiction.


Measurement of the forward energy flow in pp collisions at [Formula: see text].
The energy flow created in pp collisions at [Formula: see text] is studied within the pseudorapidity range 1.9<η<4.9 with data collected by the LHCb experiment. The measurements are performed for inclusive minimum-bias interactions, hard scattering processes and events with an enhanced or suppressed diffractive contribution. The results are compared to predictions given by Pythia-based and cosmic-ray event generators, which provide different models of soft hadronic interactions.


177Lu-octreotate therapy for neuroendocrine tumours is enhanced by Hsp90 inhibition.
177Lu-octreotate is an FDA-approved radionuclide therapy for patients with gastroenteropancreatic neuroendocrine tumours (NETs) expressing somatostatin receptors. The 177Lu-octreotate therapy has shown promising results in clinical trials by prolonging progression-free survival, but complete responses are still uncommon. The aim of this study was to improve the 177Lu-octreotate therapy by means of combination therapy. To identify radiosensitising inhibitors, two cell lines, GOT1 and P-STS, derived from small intestinal neuroendocrine tumours (SINETs), were screened with 1,224 inhibitors alone or in combination with external radiation. The screening revealed that inhibitors of Hsp90 can potentiate the tumour cell-killing effect of radiation in a synergistic fashion (GOT1; false discovery rate <3.2×10-11). The potential for Hsp90 inhibitor ganetespib to enhance the anti-tumour effect of 177Lu-octreotate in an in vivo setting was studied in the somatostatin receptor-expressing GOT1 xenograft model. The combination led to a larger decrease in tumour volume relative to monotherapies and the tumour-reducing effect was shown to be synergistic. Using patient-derived tumour cells from eight metastatic SINETs, we could show that ganetespib enhanced the effect of 177Lu-octreotate therapy for all investigated patient tumours. Levels of Hsp90 protein expression were evaluated in 767 SINETs from 379 patients. We found that Hsp90 expression was upregulated in tumour cells relative to tumour stroma in the vast majority of SINETs. We conclude that Hsp90 inhibitors enhance the tumour-killing effect of 177Lu-octreotate therapy synergistically in SINET tumour models and suggest that this potentially promising combination should be further evaluated.


Rheumatoid arthritis-associated bone erosions: evolving insights and promising therapeutic strategies.
The human immune system has evolved to recognize and eradicate pathogens, a process that is known as "host defense". If, however, the immune system does not work properly, it can mistakenly attack the body's own tissues and induce autoimmune diseases. Rheumatoid arthritis (RA) is such an autoimmune disease in which the synovial joints are predominately attacked by the immune system. Moreover, RA is associated with bone destruction and joint deformity. Although biologic agents have propelled RA treatment forward dramatically over the past 30 years, a considerable number of patients with RA still experience progressive bone damage and joint disability. That is to be expected since current RA therapies are all intended to halt inflammation but not to alleviate bone destruction. A better understanding of bone erosions is crucial to developing a novel strategy to treat RA-associated erosions. This review provides insights into RA-associated bone destruction and perspectives for future clinical interventions.


The spatial substructure of visual receptive fields in the cat's superior colliculus.
Although the direction selective properties of the superficial layer cells of the cat's superior colliculus have been extensively studied, the mechanisms underlying this property remain controversial. With the aim to understand the mechanism(s) underlying directional selectivity of collicular neurons we examined the substructure of their visual receptive fields. 1. The strength of cell responses and the direction selectivity indices varied in relation to the location of the tested region within the receptive field and the amplitude of stimulus movement. 2. Decrease of the amplitude of motion resulted in a decrease of direction selectivity index both in the group of direction-selective cells and in the group of cells classified as direction nonselective but with a directional bias. 3. The decrease of direction selectivity for small amplitude movement resulted mainly from increase in the magnitude of response in the nonpreferred direction of movement. 4. These results suggest that the receptive fields of most collicular cells are composed of subregions with different response profiles and indicate that inhibitory mechanisms dictate direction selectivity of collicular cells.


Pelvic pain in women: clinical and scientific aspects.
Pelvic pain is a common complaint of women that is frequently poorly managed. This review considers the current understanding of the mechanisms of pain perception and the development of chronic pain in the context of three gynaecological pain conditions. Recent advances in the management of these conditions are then discussed. Persistent pelvic pain is associated with central changes, reflected by alterations in psychology, brain structure and function, and dysfunction of the hypothalamic-pituitary-adrenal axis. The many similarities among the conditions support the notion that chronic pain should be treated as a symptom in its own right, however, obtaining a diagnosis remains important to patients. Few new treatments have been developed recently, however, older treatments are being subjected to more rigorous testing and improvements in phenotyping should lead to better design of clinical trials. Good quality, well designed clinical trials are urgently required to improve the treatment of pelvic pain in women. However, a variety of successful treatments exist and outcomes can be optimized by individualizing treatment strategies in the context of a multidisciplinary package.


Distinct Hippocampal versus Frontoparietal Network Contributions to Retrieval and Memory-guided Exploration.
Memory can profoundly influence new learning, presumably because memory optimizes exploration of to-be-learned material. Although hippocampus and frontoparietal networks have been implicated in memory-guided exploration, their specific and interactive roles have not been identified. We examined eye movements during fMRI scanning to identify neural correlates of the influences of memory retrieval on exploration and learning. After retrieval of one object in a multiobject array, viewing was strategically directed away from the retrieved object toward nonretrieved objects, such that exploration was directed toward to-be-learned content. Retrieved objects later served as optimal reminder cues, indicating that exploration caused memory to become structured around the retrieved content. Hippocampal activity was associated with memory retrieval, whereas frontoparietal activity varied with strategic viewing patterns deployed after retrieval, thus providing spatiotemporal dissociation of memory retrieval from memory-guided learning strategies. Time-lagged fMRI connectivity analyses indicated that hippocampal activity predicted frontoparietal activity to a greater extent for a condition in which retrieval guided exploration occurred than for a passive control condition in which exploration was not influenced by retrieval. This demonstrates network-level interaction effects specific to influences of memory on strategic exploration. These findings show how memory guides behavior during learning and demonstrate distinct yet interactive hippocampal-frontoparietal roles in implementing strategic exploration behaviors that determine the fate of evolving memory representations.


Spectral changes produced by static scattering on a system of particles.
A formula of considerable generality is derived for the spectrum of light produced by static scattering of polychromatic light on a system of particles. It applies to deterministic as well as to random distributions of monodispersed or polydispersed particles. We illustrate it by examples. It is suggested that spectral changes produced by scattering could be used for determining the structure of some scattering systems.


A newly discovered Bordetella species carries a transcriptionally active CRISPR-Cas with a small Cas9 endonuclease.
Clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated genes (cas) are widely distributed among bacteria. These systems provide adaptive immunity against mobile genetic elements specified by the spacer sequences stored within the CRISPR. The CRISPR-Cas system has been identified using Basic Local Alignment Search Tool (BLAST) against other sequenced and annotated genomes and confirmed via CRISPRfinder program. Using Polymerase Chain Reactions (PCR) and Sanger DNA sequencing, we discovered CRISPRs in additional bacterial isolates of the same species of Bordetella. Transcriptional activity and processing of the CRISPR have been assessed via RT-PCR. Here we describe a novel Type II-C CRISPR and its associated genes-cas1, cas2, and cas9-in several isolates of a newly discovered Bordetella species. The CRISPR-cas locus, which is absent in all other Bordetella species, has a significantly lower GC-content than the genome-wide average, suggesting acquisition of this locus via horizontal gene transfer from a currently unknown source. The CRISPR array is transcribed and processed into mature CRISPR RNAs (crRNA), some of which have homology to prophages found in closely related species B. hinzii. Expression of the CRISPR-Cas system and processing of crRNAs with perfect homology to prophages present in closely related species, but absent in that containing this CRISPR-Cas system, suggest it provides protection against phage predation. The 3,117-bp cas9 endonuclease gene from this novel CRISPR-Cas system is 990 bp smaller than that of Streptococcus pyogenes, the 4,017-bp allele currently used for genome editing, and which may make it a useful tool in various CRISPR-Cas technologies.


Surface markers of cloned human T cells with various cytolytic activities.
Human T cells stimulated in secondary allogeneic mixed lymphocyte culture (MLC) were cloned under limiting conditions in microculture systems using T cell growth factor and irradiated allogeneic cells. Clones with lytic activity against either phytohemagglutinin-induced blast cells bearing the stimulating alloantigen(s) (cytotoxic T lymphocyte [CTL] activity), L1210 mouse lymphoma cells coated with rabbit antibody (antibody-dependent cell-mediated cytotoxicity [ADCC]), or K562 human target cells were selected, expanded, and then analyzed for different surface markers, including rosette formation with sheep erythrocytes (E rosettes), receptors for the fc portion of IgG or IgM (Fc gamma R and Fc mu R), and a group of antigens recognized by monoclonal antibodies including Ia, 4F2, OKT8,a nd OKT4. All the cytotoxic cells were E rosette+, Ia+ and 4f2+. Expression of Fc gamma R was restricted to the clones active in ADCC. CTL clones were either OKT8+ or OKT8-. Furthermore, three of the OKT8- CTL clones were OKT4+. In addition, some cytolytic clones devoid of specific CTL activity were OKT8+. It thus appears that the claim that human CTL are OKT8+, OKT4-, and Ia- is not supported by the analysis of their phenotype at the clonal level.


Reliance on shallow soil water in a mixed-hardwood forest in central Pennsylvania.
We investigated depth of water uptake of trees on shale-derived soils in order to assess the importance of roots over a meter deep as a driver of water use in a central Pennsylvania catchment. This information is not only needed to improve basic understanding of water use in these forests but also to improve descriptions of root function at depth in hydrologic process models. The study took place at the Susquehanna Shale Hills Critical Zone Observatory in central Pennsylvania. We asked two main questions: (i) Do trees in a mixed-hardwood, humid temperate forest in a central Pennsylvania catchment rely on deep roots for water during dry portions of the growing season? (ii) What is the role of tree genus, size, soil depth and hillslope position on the depth of water extraction by trees? Based on multiple lines of evidence, including stable isotope natural abundance, sap flux and soil moisture depletion patterns with depth, the majority of water uptake during the dry part of the growing season occurred, on average, at less than ∼60 cm soil depth throughout the catchment. While there were some trends in depth of water uptake related to genus, tree size and soil depth, water uptake was more uniformly shallow than we expected. Our results suggest that these types of forests may rely considerably on water sources that are quite shallow, even in the drier parts of the growing season.


Factors affecting the metabolic production of methylguanidine.
1. Methylguanidine administered orally to normal volunteers was almost completely recovered in the urine, indicating that it is absorbed in the gastrointestinal tract and is not converted into other compounds. In normal persons at least, its urinary output therefore corresponds to its metabolic production rate plus the amount ingested. 2. In normal persons, diets based on foods not containing methylguanidine (e.g. vegetarian, protein-free and milk-egg) caused a fall in the urinary output of methylguanidine as compared with the output of the same subjects on a free diet. Conversely, higher amounts of methylguanidine were excreted on a diet rich in broth and in boiled beef, which contain large amounts of methylguanidine formed from the oxidation of creatinine, caused by boiling. 3. Oral administration of creatinine to normal volunteers induced an immediate and marked increase in urinary excretion of methylguanidine, and the ingestion of [methyl-14-C]creatinine by uraemic patients was followed by the urinary excretion of labelled methylguanidine. These findings indicate that creatinine is partly converted into methylguanidine in both normal and uraemic subjects and accounts for the high metabolic production of methylguanidine in patients with renal failure, in whom the body pool of creatinine is high. 4. Creatinine, incubated at 38 degrees C for 24 h in Krebs bicarbonate solution (pH 7-38) through which was bubbled oxygen with 15% carbon dioxide, was partially oxidized to methylguanidine. This raises the possibility that even in vivo such a conversion may occur "non-enzymatically".


Traditional and Alternative Therapies for Refractory Angina.
Refractory angina (RFA) is an unfavourable condition that is characterized with persistent angina due to reversible myocardial ischemia in patients with coronary artery disease that remains uncontrollable despite an optimal combination of pharmacological agents and revascularization. Despite significant advances in revascularization techniques and agents used in pharmacological therapy, there is still a significant population suffering from RFA and the global prevalence is even increasing. Anti- anginal treatment and secondary risk-factor modification are the traditional approaches for this group of patients. Furthermore, now there is still a large number of alternative treatment options. In order to review traditional and alternative treatment strategies in patients with RFA, we searched Pubmed for articles in English using the search terms "pharmacological therapy, refractory angina", "alternative therapy, refractory angina" between inception to June 2016. We also went through separately for each alternative treatment modality on Pubmed. To identify further articles, we handsearched related citations in review articles and commentaries. We also included data from the European Society of Cardiology (2013), and the Canadian Society of Cardiology/ Canadian Pain Society (2012) guidelines. Data show that besides traditional pharmacological agents, such as nitrates, beta- blockers or calcium channel blockers, novel antiischemic drugs and if symptoms persist, several non- invasive and/ or invasive alternative strategies may be considered. Impact of some pharmacological agents, such as rho- kinase inhibitors, and novel alternative treatment modalities, such as coronary sinus reducers, stem cell therapy, gene and protein therapy, on outcomes are still under investigation.


Causal Information-Seeking Strategies Change Across Childhood and Adolescence.
Intervening on causal systems can illuminate their underlying structures. Past work has shown that, relative to adults, young children often make intervention decisions that appear to confirm a single hypothesis rather than those that optimally discriminate alternative hypotheses. Here, we investigated how the ability to make informative causal interventions changes across development. Ninety participants between the ages of 7 and 25 completed 40 different puzzles in which they had to intervene on various causal systems to determine their underlying structures. Each puzzle comprised a three- or four-node computer chip with hidden wires. On each trial, participants viewed two possible arrangements of the chip's hidden wires and had to select a single node to activate. After observing the outcome of their intervention, participants selected a wire configuration and rated their confidence in their selection. We characterized participant choices with a Bayesian measurement model that indexed the extent to which participants selected nodes that would best disambiguate the two possible causal structures versus those that had high causal centrality in one of the two causal hypotheses but did not necessarily discriminate between them. Our model estimates revealed that the use of a discriminatory strategy increased through early adolescence. Further, developmental improvements in intervention strategy were related to changes in the ability to accurately judge the strength of evidence that interventions revealed, as indexed by participants' confidence in their selections. Our results suggest that improvements in causal information-seeking extend into adolescence and may be driven by metacognitive sensitivity to the efficacy of previous interventions in discriminating competing ideas.


A Low Power Micro Deep Brain Stimulation Device for Murine Preclinical Research.
Deep brain stimulation has emerged as an effective medical procedure that has therapeutic efficacy in a number of neuropsychiatric disorders. Preclinical research involving laboratory animals is being conducted to study the principles, mechanisms, and therapeutic effects of deep brain stimulation. A bottleneck is, however, the lack of deep brain stimulation devices that enable long term brain stimulation in freely moving laboratory animals. Most of the existing devices employ complex circuitry, and are thus bulky. These devices are usually connected to the electrode that is implanted into the animal brain using long fixed wires. In long term behavioral trials, however, laboratory animals often need to continuously receive brain stimulation for days without interruption, which is difficult with existing technology. This paper presents a low power and lightweight portable microdeep brain stimulation device for laboratory animals. Three different configurations of the device are presented as follows: 1) single piece head mountable; 2) single piece back mountable; and 3) two piece back mountable. The device can be easily carried by the animal during the course of a clinical trial, and that it can produce non-stop stimulation current pulses of desired characteristics for over 12 days on a single battery. It employs passive charge balancing to minimize undesirable effects on the target tissue. The results of bench, in-vitro, and in-vivo tests to evaluate the performance of the device are presented.


Non-classical p38 map kinase functions: cell cycle checkpoints and survival.
The p38 MAPK kinase pathway is activated in response to a wide range of cellular stress stimuli and cytokines. Our understanding of the important functions of p38 MAPK in the process of differentiation and cell death has grown considerably in the recent years and is now relatively established. Here we discuss the role of p38 MAPK in the mediation of cell cycle checkpoints and cell survival, processes that have received less attention. We describe how p38 MAPK regulates both the G2/M as well as a G1/S cell cycle checkpoint in response to cellular stress such as DNA damage. While p38 MAPK has classically been associated with the induction of apoptosis, we discuss that p38 MAPK can also mediate cell survival in specific situations, such as in response to DNA damage. It is important to recognize these less appreciated functions of p38 MAPK when considering the potential use of pharmacological inhibitors of p38 MAPK in therapeutic treatments for disease.


Distinct transcriptional control in major immunogenetic subsets of chronic lymphocytic leukemia exhibiting subset-biased global DNA methylation profiles.
Chronic lymphocytic leukemia (CLL) can be divided into prognostic subgroups based on the IGHV gene mutational status, and is further characterized by multiple subsets of cases with quasi-identical or stereotyped B cell receptors that also share clinical and biological features. We recently reported differential DNA methylation profiles in IGHV-mutated and IGHV-unmutated CLL subgroups. For the first time, we here explore the global methylation profiles of stereotyped subsets with different prognosis, by applying high-resolution methylation arrays on CLL samples from three major stereotyped subsets: the poor-prognostic subsets #1 (n = 15) and #2 (n = 9) and the favorable-prognostic subset #4 (n = 15). Overall, the three subsets exhibited significantly different methylation profiles, which only partially overlapped with those observed in our previous study according to IGHV gene mutational status. Specifically, gene ontology analysis of the differentially methylated genes revealed a clear enrichment of genes involved in immune response, such as B cell activation (e.g., CD80, CD86 and IL10), with higher methylation levels in subset #1 than subsets #2 and #4. Accordingly, higher expression of the co-stimulatory molecules CD80 and CD86 was demonstrated in subset #4 vs. subset #1, pointing to a key role for these molecules in the crosstalk of CLL subset #4 cells with the microenvironment. In summary, investigation of three prototypic, stereotyped CLL subsets revealed distinct DNA methylation profiles for each subset, which suggests subset-biased patterns of transcriptional control and highlights a key role for epigenetics during leukemogenesis.


VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers.
To compare the clinical and cost-effectiveness of two different compression bandages for the healing of venous leg ulcers. A pragmatic, randomised controlled trial with an economic evaluation. Community, district nurse-led services; community leg ulcer clinics; hospital leg ulcer clinics with community outreach. A range of urban and rural settings in England and Scotland. Patients with a venous leg ulcer of at least 1-week's duration, at least 1 cm in length or width and an ankle:brachial pressure index of at least 0.8. The four-layer bandage (4LB) (which is multilayer elastic compression) compared with the short-stretch bandage (SSB) (multilayer, inelastic compression). The primary end-point was complete healing of all the ulcers on the trial leg. Secondary outcomes were the proportion of patients healed at 12 and 24 weeks, rate of recurrence, costs of leg ulcer treatment and quality of life. Between April 1999 and December 2000 the trial recruited 387 people aged from 23 to 97 years at trial entry. The majority of patients in this trial (82%; 316/387) had a reference ulcer of area </=10 cm(2). To test the difference over time of Kaplan--Meier curves for the two bandage groups, the distribution of the cumulative times to healing of individuals in the two trial groups was compared using the log-rank test. The difference in the distribution of cumulative healing times between the individuals in the two groups was not statistically significant at the 5% level. Adjusting for the effects of variables which may influence healing (centre, baseline ulcer area, duration, episodes, ankle mobility, weight) in a Cox proportional hazards model, a statistically significant treatment effect in favour of the 4LB was identified. At any point in time, the probability of healing for individuals in the SSB treatment arm is significantly lower than that for people treated with the 4LB. Our base case economic analysis showed that the 4LB is the dominant strategy, that is, it is associated with a greater health benefit and lower costs than the SSB, although the differences are not statistically significant. This result is explained largely by the greater number of community nurse visits required by participants in the short-stretch arm. The 4LB, which is currently the UK standard compression bandage for people with venous leg ulcers, was more clinically and cost-effective than the SSB. The bandage costs were less important than the costs of treatment visits, and patients in SSBs required more treatment overall. Generally, this trial supports the use of the 4LB in preference to the SSB. Recommendations for future research include: exploration of the relationship between bandager skill, application technique and ulcer healing; the relative cost-effectiveness of community leg ulcer clinics; and the study of nurse decision-making in venous ulcer management.


The characteristics of involuntary and voluntary autobiographical memories in depressed and never depressed individuals.
This study compares involuntary and voluntary autobiographical memories in depressed and never depressed individuals. Twenty depressed and twenty never depressed individuals completed a memory diary; recording their reactions to 10 involuntary and 10 voluntary memories over 14-30 days. Psychiatric status (Structured Clinical Interview for DSM-IV, SCID-1), psychopathology, rumination and avoidance were assessed. For both groups, involuntary memories more frequently lead to strong reactions than voluntarily memories. For both modes of retrieval, depressed individuals reported more frequent negative reactions than never depressed individuals and rated memories as more central to identity with higher levels of rumination and avoidance. Depressed individuals retrieved both positive and negative memories during involuntary retrieval. These findings support the view that involuntary memory retrieval represents a basic mode of retrieval during healthy and disordered cognition, and that during depression, both involuntary and voluntary memories are central to identity and associated with rumination and avoidance.


An investigation of the role of auditory cortex in sound localization using muscimol-releasing Elvax.
Lesion studies suggest that primary auditory cortex (A1) is required for accurate sound localization by carnivores and primates. In order to elucidate further its role in spatial hearing, we examined the behavioural consequences of reversibly inactivating ferret A1 over long periods, using Elvax implants releasing the GABA(A) receptor agonist muscimol. Sub-dural polymer placements were shown to deliver relatively constant levels of muscimol to underlying cortex for >5 months. The measured diffusion of muscimol beneath and around the implant was limited to 1 mm. Cortical silencing was assessed electrophysiologically in both auditory and visual cortices. This exhibited rapid onset and was reversed within a few hours of implant removal. Inactivation of cortical neurons extended to all layers for implants lasting up to 6 weeks and throughout at least layers I-IV for longer placements, whereas thalamic activity in layer IV appeared to be unaffected. Blockade of cortical neurons in the deeper layers was restricted to < or = 500 microm from the edge of the implant, but was usually more widespread in the superficial layers. In contrast, drug-free Elvax implants had little discernible effect on the responses of the underlying cortical neurons. Bilateral implants of muscimol-Elvax over A1 produced significant deficits in the localization of brief sounds in horizontal space and particularly a reduced ability to discriminate between anterior and posterior sound sources. The performance of these ferrets gradually improved over the period in which the Elvax was in place and attained that of control animals following its removal. Although similar in nature, these deficits were less pronounced than those caused by cortical lesions and suggest a specific role for A1 in resolving the spatial ambiguities inherent in auditory localization cues.


Six-week treatment with Ukrain in rabbits. Part III: Serum levels of thyroid hormones.
The influence of 6-week treatment with Ukrain at doses of 0.3, 1.5 and 3.0 mg/kg i.v. on serum levels of thyroid hormones, i.e., thyroxine and triiodothyronine, was studied in rabbits of both sexes. Ukrain affected the serum levels of both hormones in males. An increase in the thyroxine level was found after Ukrain used at a dose of 1.5 and 3.0 mg/kg i.v., whereas increased triiodothyronine was noted when Ukrain was given at all studied doses. In females the thyroxine level was not altered by Ukrain administration, whereas the triiodothyronine concentration was increased following Ukrain at 0.3, 1.5 and 3.0 mg/kg i.v. it is probable the altered thyroid hormone levels as a result of Ukrain application may contribute to the drug's potent immunomodulatory action.


Morphometry of Proximal Femur in Indian Population.
Total hip arthroplasty is a commonly performed surgery now-a-day. There are regional and racial variations in the stature of the population worldwide. So there is always need of population specific data for making best fit prosthesis. The present study was done to measure the parameters of proximal femur and to analyse their correlation by using standard statistical analysis. Ninety one dry bones (44 left and 47 right) were used. Femur Head Diameter (FHD), Femur Neck Length (FNL), Femur Neck Diameter (FND), Femur Neck Thickness (FNT), Cervicodiaphyseal Angle (CDA) was directly measured with the help of anthropometric instruments. Femur Head Offset (FHO) and Vertical Offset (VO) were measured in the anteroposterior digital photographs. Normally distributed variables were compared using Student's t-test (Unpaired data) to analyse significant effect. There was a significant difference between right and left side of FND and CDA. Pearson correlation coefficient was used to analyse the relationship among variables. FHO had high correlation with the VO (0.687, p<0.001). These parameters can be used for designing the prosthesis and plates for hip joint reconstructive surgeries suitable for Indian population.


JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress.
c-myc and p53 networks control proliferation, differentiation, and apoptosis and are responsive to, and cross-regulate a variety of stresses and metabolic and biosynthetic processes. At c-myc, the far upstream element binding protein (FBP) and FBP-interacting repressor (FIR) program transcription by looping to RNA polymerase II complexes engaged at the promoter. Another FBP partner, JTV1/AIMP2, a structural subunit of a multi-aminoacyl-tRNA synthetase (ARS) complex, has also been reported to stabilize p53 via an apparently independent mechanism. Here, we show that in response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with FBP and co-activates the transcription of a new FBP target, ubiquitin-specific peptidase 29 (USP29). A previously uncharacterized deubiquitinating enzyme, USP29 binds to, cleaves poly-ubiquitin chains from, and stabilizes p53. The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress.


Microbial metabolism mediates interactions between dissolved organic matter and clay minerals in streamwater.
Sorption of organic molecules to mineral surfaces is an important control upon the aquatic carbon (C) cycle. Organo-mineral interactions are known to regulate the transport and burial of C within inland waters, yet the mechanisms that underlie these processes are poorly constrained. Streamwater contains a complex and dynamic mix of dissolved organic compounds that coexists with a range of organic and inorganic particles and microorganisms. To test how microbial metabolism and organo-mineral complexation alter amino acid and organic carbon fluxes we experimented with (13)C-labelled amino acids and two common clay minerals (kaolinite and montmorillonite). The addition of (13)C-labelled amino acids stimulated increased microbial activity. Amino acids were preferentially mineralized by the microbial community, concomitant with the leaching of other (non-labelled) dissolved organic molecules that were removed from solution by clay-mediated processes. We propose that microbial processes mediate the formation of organo-mineral particles in streamwater, with potential implications for the biochemical composition of organic matter transported through and buried within fluvial environments.


Intravenous Arginine Administration Downregulates NLRP3 Inflammasome Activity and Attenuates Acute Kidney Injury in Mice with Polymicrobial Sepsis.
Acute kidney injury (AKI) is a major complication of sepsis. Nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasomes are multiprotein complexes that mediate septic AKI. L-arginine (Arg) is a conditionally essential amino acid in catabolic conditions and a substrate for nitric oxide (NO) production; however, its use in sepsis is controversial. This study investigated the effect of intravenous Arg supplementation on modulating NLRP3 inflammasome activity in relation to septic AKI. Mice were divided into normal control (NC), sham, sepsis saline (SS), and sepsis Arg (SA) groups. In order to investigate the role of NO, L-N6-(1-iminoethyl)-lysine hydrochloride (L-NIL), an inducible NO synthase inhibitor, was administered to the sepsis groups. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg via tail vein 1 h after CLP. Mice were sacrificed at 6, 12, and 24 h after sepsis. The results showed that compared to the NC group, septic mice had higher plasma kidney function parameters and lower Arg levels. Also, renal NLRP3 inflammasome protein expression and tubular injury score increased. After Arg treatment, plasma Arg and NO levels increased, kidney function improved, and expressions of renal NLRP3 inflammasome-related proteins were downregulated. Changes in plasma NO and renal NLRP3 inflammasome-related protein expression were abrogated when L-NIL was given to the Arg sepsis groups. Arg plus L-NIL administration also attenuated kidney injury after CLP. The findings suggest that intravenous Arg supplementation immediately after sepsis restores plasma Arg levels and is beneficial for attenuating septic AKI, partly via NO-mediated NLRP3 inflammasome inhibition.


Aspect ratio dependent air stability of PbSe nanorods and photovoltaic applications.
Development of unique strategies to overcome Shockley-Queisser (SQ) limit in solar cells has gained a great deal of interest. Multiple exciton generation (MEG) process has been considered as one of the best approaches to the SQ limitation. In this respect, PbSe quantum dots (QDs) and nanorods (NRs) have been regarded as promising solar energy harvesting materials owing to their noticeable MEG yields. Although air stability has been regarded as one of the main disadvantage of PbSe QDs, no study has pointed out to the air sensitivity of PbSe NRs yet. Here, we reveal the effect of aspect ratio on air sensitivity and optical properties of PbSe NRs and discover that NRs with higher aspect ratios are more air stable, attributed to the reduced density of NR ends with air sensitive {100} facets. Furthermore, a band offset was created by utilization of tetrabutylammonium iodide and 1,2-ethanedithiol ligands in cell designs. We found that solar cells based on pristine PbSe NRs are limited by low open circuit voltages due to leakage current pathways. On the other hand, modified cells comprising light absorbing layers prepared by blending NRs and QDs and hole transporting QD layer exhibit a 10-fold improvement in solar cell efficiency.


Membrane transporters and folate homeostasis: intestinal absorption and transport into systemic compartments and tissues.
Members of the family of B9 vitamins are commonly known as folates. They are derived entirely from dietary sources and are key one-carbon donors required for de novo nucleotide and methionine synthesis. These highly hydrophilic molecules use several genetically distinct and functionally diverse transport systems to enter cells: the reduced folate carrier, the proton-coupled folate transporter and the folate receptors. Each plays a unique role in mediating folate transport across epithelia and into systemic tissues. The mechanism of intestinal folate absorption was recently uncovered, revealing the genetic basis for the autosomal recessive disorder hereditary folate malabsorption, which results from loss-of-function mutations in the proton-coupled folate transporter gene. It is therefore now possible to piece together how these folate transporters contribute, both individually and collectively, to folate homeostasis in humans. This review focuses on the physiological roles of the major folate transporters, with a brief consideration of their impact on the pharmacological activities of antifolates.


The faculty advisor role: an imperative for student retention.
The decline in applicants to schools of nursing emphasizes the importance of retaining those students who do enroll. The authors review factors affecting student attrition and retention in academic settings. They then present an ideal model for enhancing student retention through effective, individualized, and consistent student advising.


The formation and fragmentation of disks around primordial protostars.
The very first stars to form in the universe heralded an end to the cosmic dark ages and introduced new physical processes that shaped early cosmic evolution. Until now, it was thought that these stars lived short, solitary lives, with only one extremely massive star, or possibly a very wide binary system, forming in each dark-matter minihalo. Here we describe numerical simulations that show that these stars were, to the contrary, often members of tight multiple systems. Our results show that the disks that formed around the first young stars were unstable to gravitational fragmentation, possibly producing small binary and higher-order systems that had separations as small as the distance between Earth and the Sun.


First description of agonist and antagonist IP-10 in urine of patients with active TB.
Biomarkers for tuberculosis (TB) diagnosis and clinical management are needed to defeat TB. In chronic hepatitis, patients not responding to interferon/ribavirin treatment had high levels of an antagonist form of IP-10. Recently, antagonist IP-10 has been shown to be involved also in TB pathogenesis. Here, we investigated IP-10 agonist/antagonist forms as potential inflammatory biomarkers to support TB diagnosis and monitoring. Total IP-10 and its agonist/antagonist forms were measured by SIMOA digital ELISA in urine obtained from patients with active TB at baseline and after treatment. Healthy donors (HD) and patients with pneumonia were enrolled as controls. Patients with active TB had significantly higher levels of total and agonist IP-10 at baseline compared to HD; conversely, no differences were observed between IP-10 levels in active TB vs pneumonia. Moreover, in active TB a decline of total urine IP-10 was observed at therapy completion; agonist/antagonist forms reflected this decline although their differences were not statistically significant. We showed for the first time that agonist/antagonist IP-10 forms are measurable in urine. IP-10 levels associate with TB and pneumonia disease, suggesting their association with acute inflammation. Further studies are needed to assess their role to monitor TB treatment efficacy.


Road crash trends for young drivers in New South Wales, Australia, from 1997 to 2007.
The objective of this article was to explore overall crash and injury trends over the past decade for young drivers residing in New South Wales (NSW), Australia, including gender and age disparities. Passenger vehicle crashes for drivers aged 17-25 occurring during 1997-2007 were extracted from the state crash database to calculate crash rates (per licensed driver). Generalized linear models were used to examine crash trends over time by severity of driver injury, adjusting for age, gender, rurality of residence, and socioeconomic status. Yearly adjusted relative risks of crash by gender and by age group were also examined over the study period. Young driver noninjury and fatality rates significantly decreased by an average of 4 percent (95% CI: 4-5) and 5 percent (95% CI: 0-9) respectively each year from 1997 to 2007. Young driver injury rates significantly increased by about 12 percent (95% CI: 9-14) to the year 2001 and then significantly decreased. The relative risk of crash (regardless of driver injury) for males compared to females significantly decreased over time. Compared to drivers aged 21-25, drivers aged 17 and particularly 18- to 20-year-olds had significantly and consistently higher crash risks across the study period. Overall, there has been a significant decline in young driver crashes in NSW over the last decade. Regardless of injury severity, males' risk of crash has reduced more than female young drivers, but drivers aged 17 continue to be at higher risk. These findings provide feedback on potential road safety successes and areas needing specific interventions for future improvements.


Hygiene and sanitation among ethnic minorities in Northern Vietnam: does government promotion match community priorities?
Improving sanitation and hygiene to prevent infectious diseases is of high priority in developing countries. This study attempts to gain in-depth understanding of hygiene and sanitation perceptions and practices among four Ethnic Minority Groups (EMGs) in a rural area of northern Vietnam. It is based on extensive participatory observations in 4 villages and 20 case households over a period of six months (May-October 2008). In addition, 10 key informants and 60 household-members were interviewed and 4 focus group discussions conducted. The study found that among the four selected EMGs the cultural perceptions of hygiene and sanitation which inform everyday hygiene practices did not differ substantially and were similar to hygiene explanations found in the rural majority population elsewhere in Vietnam. However, the difficult living conditions, particularly in highland communities, reinforce a sense of marginalization among the EMGs, which had great impact on how they perceive and respond to government sanitation interventions. The enclosed latrines promoted by authorities are met with reluctance by the EMGs due to cultural perceptions of the body as permeable and therefore, vulnerable to 'dirty air' such as bad smells from human faeces. In addition, the prioritization of specific sanitation hardware solutions by the central government aimed at increasing coverage creates expectations and dependency among the EMGs that hygiene 'comes from the outside society', resulting in low levels of community initiated actions. Based on these findings, we suggest that future hygiene promotion strategies aim for a closer match between community priorities and government hygiene policies, e.g. by allowing for a larger diversity of low-cost sanitation solutions. Scaling up participatory community-based hygiene promotion is also recommended to curb dependency and spark initiatives in ethnic minority communities. Finally, interventions should focus on hygiene "software"--promoting hygiene behaviour changes known to effectively prevent hygiene related diseases.


UCSF Chimera--a visualization system for exploratory research and analysis.
The design, implementation, and capabilities of an extensible visualization system, UCSF Chimera, are discussed. Chimera is segmented into a core that provides basic services and visualization, and extensions that provide most higher level functionality. This architecture ensures that the extension mechanism satisfies the demands of outside developers who wish to incorporate new features. Two unusual extensions are presented: Multiscale, which adds the ability to visualize large-scale molecular assemblies such as viral coats, and Collaboratory, which allows researchers to share a Chimera session interactively despite being at separate locales. Other extensions include Multalign Viewer, for showing multiple sequence alignments and associated structures; ViewDock, for screening docked ligand orientations; Movie, for replaying molecular dynamics trajectories; and Volume Viewer, for display and analysis of volumetric data. A discussion of the usage of Chimera in real-world situations is given, along with anticipated future directions. Chimera includes full user documentation, is free to academic and nonprofit users, and is available for Microsoft Windows, Linux, Apple Mac OS X, SGI IRIX, and HP Tru64 Unix from http://www.cgl.ucsf.edu/chimera/.


From urban municipalities to polar bioremediation: the characterisation and contribution of biogenic minerals for water treatment.
Minerals of biological origin have shown significant potential for the separation of contaminants from water worldwide. This study details the contribution of biologically derived minerals to water treatment operations, with a focus on filtration media from urban municipalities and remote cold regions. The results support biofilm-embedded iron and manganese to be the building blocks of biogenic mineral development on activated carbon and nutrient-amended zeolites. The presence of similar iron and manganese oxidising bacterial species across all filter media supports the analogous morphologies of biogenic minerals between sites and suggests that biological water treatment processes may be feasible across a range of climates. This is the first time the stages of biogenic mineral formation have been aligned with comprehensive imaging of the biofilm community and bacterial identification; especially with respect to cold regions. Where biogenic mineral formation occurs on filter media, the potential exists for enhanced adsorption for a range of organic and inorganic contaminants and improved longevity of filter media beyond the adsorption or exchange capacities of the raw material.


The effect of a nanofiber-hydrogel composite on neural tissue repair and regeneration in the contused spinal cord.
An injury to the spinal cord causes long-lasting loss of nervous tissue because endogenous nervous tissue repair and regeneration at the site of injury is limited. We engineered an injectable nanofiber-hydrogel composite (NHC) with interfacial bonding to provide mechanical strength and porosity and examined its effect on repair and neural tissue regeneration in an adult rat model of spinal cord contusion. At 28 days after treatment with NHC, the width of the contused spinal cord segment was 2-fold larger than in controls. With NHC treatment, tissue in the injury had a 2-fold higher M2/M1 macrophage ratio, 5-fold higher blood vessel density, 2.6-fold higher immature neuron presence, 2.4-fold higher axon density, and a similar glial scar presence compared with controls. Spared nervous tissue volume in the contused segment and hind limb function was similar between groups. Our findings indicated that NHC provided mechanical support to the contused spinal cord and supported pro-regenerative macrophage polarization, angiogenesis, axon growth, and neurogenesis in the injured tissue without any exogenous factors or cells. These results motivate further optimization of the NHC and delivery protocol to fully translate the potential of the unique properties of the NHC for treating spinal cord injury.


The bloodsucking biting midges of Argentina (Diptera: Ceratopogonidae).
A key is presented for the identification of the adults of 54 species of bloodsucking ceratopogonids, 51 of which are known inhabitants of Argentina, and Culicoides uruguayensis Ronderos, C. pifanoi Ortiz, and C. trilineatus Fox, which are known to occur in bordering Uruguay and Paraguay. Wing photographs are provided of females of the 45 species of Culicoides. Three new species of Culicoides Latreille from Northeastern Argentina are described and illustrated: C. austroparaensis Spinelli, C. bachmanni Spinelli, and C. williamsi Spinelli. The following six species are recorded for the first time from Argentina and/or bordering localities in Paraguay: Leptoconops brasiliensis (Lutz), C. gabaldoni Ortiz, C. ginesi Ortiz, C. pifanoi Ortiz, C. pseudocrescentis Tavares and Luna Dias, and C. trilineatus; and C. estevezae Ronderos and Spinelli is newly recorded from Misiones province of Argentina. C. lopesi Barretto is excluded from the Argentinean ceratopogonid fauna.


Contact evaluation and isoniazid preventive therapy among close and household contacts of tuberculosis patients in Lima, Peru: an analysis of routine data.
Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5 years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19 years. Of 191 eligible contacts <5 years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19 years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5 years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19 year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7 years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5 year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19 years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5 year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19 years old), and, only for those 5-19 years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.


Association of clinical symptomatic hypoglycemia with cardiovascular events and total mortality in type 2 diabetes: a nationwide population-based study.
Hypoglycemia is associated with serious health outcomes for patients treated for diabetes. However, the outcome of outpatients with type 2 diabetes who have experienced hypoglycemia episodes is largely unknown. The study population, derived from the National Health Insurance Research Database released by the Taiwan National Health Research Institutes during 1998-2009, comprised 77,611 patients with newly diagnosed type 2 diabetes. We designed a prospective study consisting of randomly selected hypoglycemic type 2 diabetic patients and matched type 2 diabetic patients without hypoglycemia. We investigated the relationships of hypoglycemia with total mortality and cardiovascular events, including stroke, coronary heart disease, cardiovascular diseases, and all-cause hospitalization. There were 1,844 hypoglycemic events (500 inpatients and 1,344 outpatients) among the 77,611 patients. Both mild (outpatient) and severe (inpatient) hypoglycemia cases had a higher percentage of comorbidities, including hypertension, renal diseases, cancer, stroke, and heart disease. In multivariate Cox regression models, including diabetes treatment adjustment, diabetic patients with hypoglycemia had a significantly higher risk of cardiovascular events during clinical treatment periods. After constructing a model adjusted with propensity scores, mild and severe hypoglycemia still demonstrated higher hazard ratios (HRs) for cardiovascular diseases (HR 2.09 [95% CI 1.63-2.67]), all-cause hospitalization (2.51 [2.00-3.16]), and total mortality (2.48 [1.41-4.38]). Symptomatic hypoglycemia, whether clinically mild or severe, is associated with an increased risk of cardiovascular events, all-cause hospitalization, and all-cause mortality. More attention may be needed for diabetic patients with hypoglycemic episodes.


Theory-based psychosocial factors that discriminate between weight-loss success and failure over 6 months in women with morbid obesity receiving behavioral treatments.
To improve success rates of behavioral weight-loss treatments, a better understanding of psychosocial factors that discriminate between weight-loss success and failure is required. The inclusion of cognitive-behavioral methods and manageable amounts of exercise might induce greater improvements than traditional methods of education in healthy eating practices. Women with morbid obesity [body mass index (BMI) ≥40 kg/m(2)] were recruited for a treatment of supported exercise paired with either a cognitive-behavioral or an educational approach to eating change over 6 months. They were classified as either successful with (i.e., at least 5 % loss; n = 40) or failed at (no loss, or weight gain; n = 43) weight loss. Discriminate function analysis incorporated theory-based models of 1 (self-efficacy), 5 (self-efficacy, self-regulation, mood, physical self-concept, body satisfaction), and 3 (self-efficacy, self-regulation, mood) psychosocial predictors at both month 6, and change from baseline-month 6. All three models significantly discriminated weight-loss success/failure (66, 88, and 87 % for success; and 81, 87, and 88 % for failure, respectively). Self-regulation had the strongest correlations within the multi-predictor models (0.90-0.96), and all variables entered were above the standard of 0.30 set for relevance. Participants in the cognitive-behavioral nutrition group demonstrated significantly greater improvements in all psychosocial variables and success with weight loss. Completing at least two sessions of exercise per week predicted success/failure with weight loss better than overall volume of exercise. New and relevant findings regarding treatment-induced psychosocial changes might be useful in the architecture of more successful behavioral weight-loss interventions.


Estimating phycocyanin pigment concentration in productive inland waters using Landsat measurements: a case study in Lake Dianchi.
Using remote sensing reflectance (R(rs)(λ), sr(-1)) and phycocyanin (PC, mg m(-3)) pigment data as well as other bio-optical data collected from two cruises in September and December 2009 in Lake Dianchi (a typical plateau lake of China), we developed a practical approach to estimate PC concentrations that could be applied directly to Landsat measurements. The visible and near-IR bands as well as their band ratios of simulated Landsat data were used as inputs to the algorithms, where the algorithm coefficients for each Landsat sensor were determined through multivariate regressions. The coefficients of determination (R(2)) between the R(rs)-modeled and measured PC were all > 0.97 for the spectral bands corresponding to Landsat 8 OLI, Landsat 7 ETM + , Landsat 5 TM, and Landsat 4 TM, with mean absolute percentage errors (MAPE) < 10% for PC ranging between ~80 and 700 mg m(-3) (n = 14). The algorithms were further evaluated using an independent data set (n = 14), yielding larger but still acceptable MAPE (~30%) for PC ranging between ~80 and 500 mg m(-3). Application of the approach to Landsat 8 measurements over Lake Dianchi suggests potential use of the approach for periodical assessment of the lake's bloom conditions, yet its empirical nature together with the lack of specific narrow bands on Landsat sensors to explicitly account for the PC absorption around 625 nm calls for extra caution when applied to other eutrophic lakes.


High-throughput monitoring of major cell functions by means of lensfree video microscopy.
Quantification of basic cell functions is a preliminary step to understand complex cellular mechanisms, for e.g., to test compatibility of biomaterials, to assess the effectiveness of drugs and siRNAs, and to control cell behavior. However, commonly used quantification methods are label-dependent, and end-point assays. As an alternative, using our lensfree video microscopy platform to perform high-throughput real-time monitoring of cell culture, we introduce specifically devised metrics that are capable of non-invasive quantification of cell functions such as cell-substrate adhesion, cell spreading, cell division, cell division orientation and cell death. Unlike existing methods, our platform and associated metrics embrace entire population of thousands of cells whilst monitoring the fate of every single cell within the population. This results in a high content description of cell functions that typically contains 25,000 - 900,000 measurements per experiment depending on cell density and period of observation. As proof of concept, we monitored cell-substrate adhesion and spreading kinetics of human Mesenchymal Stem Cells (hMSCs) and primary human fibroblasts, we determined the cell division orientation of hMSCs, and we observed the effect of transfection of siCellDeath (siRNA known to induce cell death) on hMSCs and human Osteo Sarcoma (U2OS) Cells.


Normal regional distribution of cerebral blood flow in dogs: comparison between (99m) Tc-ethylcysteinate dimer and (99m) Tc- hexamethylpropylene amine oxime single photon emission computed tomography.
Functional imaging provides important insights into canine brain pathologies such as behavioral problems. Two (99m) Tc-labeled single photon emission computed tomography (SPECT) cerebral blood flow tracers-ethylcysteinate dimer (ECD) and hexamethylpropylene amine oxime (HMPAO)-are commonly used in human medicine and have been used previously in dogs but intrasubject comparison of both tracers in dogs is lacking. Therefore, this study investigated whether regional distribution differences between both tracers occur in dogs as is reported in humans. Eight beagles underwent two SPECT examinations first with (99m) Tc-ECD and followed by (99m) Tc-HMPAO. SPECT scanning was performed with a triple head gamma camera equipped with ultrahigh resolution parallel hole collimators. Images were reconstructed using filtered backprojection with a Butterworth filter. Emission data were fitted to a template permitting semiquantification using predefined regions or volumes of interest (VOIs). For each VOI, perfusion indices were calculated by normalizing the regional counts per voxel to total brain counts per voxel. The obtained perfusion indices for each region for both tracers were compared with a paired Student's T-test. Significant (P < 0.05) regional differences were seen in the subcortical region and the cerebellum. Both tracers can be used to visualize regional cerebral blood flow in dogs, however, due to the observed regional differences, they are not entirely interchangeable.


Concentrations of the domestic house dust mite allergen Der p I after treatment with solidified benzyl benzoate (Acarosan) or liquid nitrogen.
Various methods of killing the house dust mite to reduce exposure to allergen are being promoted even though complete data on their effects on allergen concentrations are not available. A study was designed to measure the concentrations of the main house dust mite allergen Der pI in homes treated with either solidified benzyl benzoate (Acarosan) or liquid nitrogen. Der pI concentrations were measured in dust collected from mattresses, bedroom carpets, and living room carpets in 10 houses treated with Acarosan and 10 houses treated with liquid nitrogen. Samples were collected before the treatment (in July 1990) and three and six months afterwards (October 1990 and January 1991). Forty untreated houses were concurrently sampled as controls. Der pI concentrations were similar in the three groups at baseline. No significant fall was seen in either of the two treated groups three or six months after treatment. Concentrations in the control houses increased significantly--twofold to threefold in dust sampled from mattresses and bedroom carpets between baseline and October 1990. This increase was not seen in either of the treated groups of houses, but there was no significant difference in the Derp pI concentrations in these houses and the control houses from any site at any time point. Neither Acarosan nor liquid nitrogen reduced the concentrations of Der pI for as long as six months after application. A small effect was probably present as the rise seen in control houses in the three month samples was not found in the treated houses. This effect, however, is likely to be of little clinical importance and also to be transient as the trend was lost by six months.


Suitability of ozone pre-treatment for amoxicillin wastewater.
This study deals with the ozonation of amoxicillin in real pharmaceutical wastewater and its efficacy as a pre-treatment, prior to biological degradation by a mixed culture of bacteria in a sequencing batch reactor (SBR). An ozone utilization of 0.27 g/g-COD (chemical oxygen demand) lowered the pH of the wastewater to 6.6, reduced the specific ultraviolet absorption by 43% and increased the biochemical oxygen demand (BOD) concentration by 37%. The BOD:COD ratio became equal to 0.89, making the ozonated wastewater seemingly suitable for biological treatment; however, when the ozonated effluent was fed to the SBR, the reactor performance degraded, an effect which was attributed to ozonation by-products. In conclusion, ozonation might not be a suitable pre-treatment for pharmaceutical wastewater containing amoxicillin, and biotreatment with properly acclimated biomass may be a better option for treatment of such pharmaceutical wastewater.


Stroke incidence and mortality trends in US communities, 1987 to 2011.
Prior studies have shown decreases in stroke mortality over time, but data on validated stroke incidence and long-term trends by race are limited. To study trends in stroke incidence and subsequent mortality among black and white adults in the Atherosclerosis Risk in Communities (ARIC) cohort from 1987 to 2011. Prospective cohort study of 14,357 participants (282,097 person-years) free of stroke at baseline was facilitated in 4 different US communities. Participants were recruited for the purpose of studying all stroke hospitalizations and deaths and for collection of baseline information on cardiovascular risk factors (via interviews and physical examinations) in 1987-1989. Participants were followed up (via examinations, annual phone interviews, active surveillance of discharges from local hospitals, and linkage with the National Death Index) through December 31, 2011. The study physician reviewers adjudicated all possible strokes and classified them as definite or probable ischemic or hemorrhagic events. Trends in rates of first-ever stroke per 10 years of calendar time were estimated using Poisson regression incidence rate ratios (IRRs), with subsequent mortality analyzed using Cox proportional hazards regression models and hazard ratios (HRs) overall and by race, sex, and age divided at 65 years. Among 1051 (7%) participants with incident stroke, there were 929 with incident ischemic stroke and 140 with incident hemorrhagic stroke (18 participants had both during the study period). Crude incidence rates were 3.73 (95% CI, 3.51-3.96) per 1000 person-years for total stroke, 3.29 (95% CI, 3.08-3.50) per 1000 person-years for ischemic stroke, and 0.49 (95% CI, 0.41-0.57) per 1000 person-years for hemorrhagic stroke. Stroke incidence decreased over time in white and black participants (age-adjusted IRRs per 10-year period, 0.76 [95% CI, 0.66-0.87]; absolute decrease of 0.93 per 1000 person-years overall). The decrease in age-adjusted incidence was evident in participants age 65 years and older (age-adjusted IRR per 10-year period, 0.69 [95% CI, 0.59-0.81]; absolute decrease of 1.35 per 1000 person-years) but not evident in participants younger than 65 years (age-adjusted IRR per 10-year period, 0.97 [95% CI, 0.76-1.25]; absolute decrease of 0.09 per 1000 person-years) (P = .02 for interaction). The decrease in incidence was similar by sex. Of participants with incident stroke, 614 (58%) died through 2011. The mortality rate was higher for hemorrhagic stroke (68%) than for ischemic stroke (57%). Overall, mortality after stroke decreased over time (hazard ratio [HR], 0.80 [95% CI, 0.66-0.98]; absolute decrease of 8.09 per 100 strokes after 10 years [per 10-year period]). The decrease in mortality was mostly accounted for by the decrease at younger than age 65 years (HR, 0.65 [95% CI, 0.46-0.93]; absolute decrease of 14.19 per 100 strokes after 10 years [per 10-year period]), but was similar across race and sex. In a multicenter cohort of black and white adults in US communities, stroke incidence and mortality rates decreased from 1987 to 2011. The decreases varied across age groups, but were similar across sex and race, showing that improvements in stroke incidence and outcome continued to 2011.