An educational intervention, involving feedback of routinely collected computer data, to improve cardiovascular disease management in UK primary care.
To report the lessons learned from eight years of feeding back routinely collected cardiovascular data in an educational context There are distinct educational and technical components. The educational component provides peer-led learning opportunities based on comparative analysis of quality of care, as represented in computer records. The technical part ensures that relevant evidence-based audit criteria are identified; an appropriate dataset is extracted and processed to facilitate quality improvement. Anonymised data are used to provide inter-practice comparisons, with lists of identifiable patients who need interventions left in individual practices. The progressive improvement in cholesterol management in ischaemic heart disease (IHD) is used as an exemplar of the changes achieved. Over three iterations of the cardiovascular programme the standardised prevalence of IHD recorded in GP computer systems rose from 3.8% to 4.0%. Cholesterol recording rose from 47.6% to 89.0%; and the mean cholesterol level fell from 5.18 to 4.67 mmol/L; while statin prescribing rose from 46% to 57% to 68%. The atrial fibrillation, heart failure and renal programmes (more people with chronic kidney disease go on to die from cardiovascular cause than from end-stage renal disease) are used to demonstrate the range of cardiovascular interventions amenable to this approach. Technical progress has meant that larger datasets can be extracted and processed. Feedback of routinely collected data in an educational context is acceptable to practitioners and results in quality improvement. Further research is needed to assess its utility as a strategy and cost-effectiveness compared with other methods.


Dissociating explicit and implicit category knowledge with fMRI.
Neuroimaging of healthy volunteers identified separate neural systems supporting the expression of category knowledge depending on whether the learning mode was intentional or incidental. The same visual category was learned either intentionally or implicitly by two separate groupsof participants. During a categorization test, functional magnetic resonance imaging (fMRI) was used to compare brain activity evoked by category members and nonmembers. After implicit learning, when participants had learned the category incidentally, decreased occipital activity was observed for novel categorical stimuli compared with noncategorical stimuli. In contrast, after intentional learning, novel categorical stimuli evoked increased activity in the hippocampus, right prefrontal cortex, left inferior temporal cortex, precuneus, and posterior cingulate. Even though the categorization test was identical in the two conditions, the differences in brain activity indicate differing representations of category knowledge depending on whether the category had been learned intentionally or implicitly.


Staining internal limiting membrane with a mixture of BBG and sodium hyaluronate.
To evaluate the intraoperative applicability and safety of a mixture of brilliant blue G and sodium hyaluronate (visco-BBG) for staining the inner limiting membrane (ILM). A retrospective consecutive case series. Seventy-four eyes that had undergone ILM peeling were studied. During vitrectomy, ILM peeling with visco-BBG (visco-BBG group) was performed on 40 eyes; 12 with a macular hole (MH), 26 with an epimacular membrane (ERM) and 2 with a retinal detachment due to a MH (MHRD). ILM peeling with BBG dissolved in balanced salt solution (BSS-BBG group) was performed on 34 eyes; 9 with a MH, 23 with an ERM and 2 with a MHRD. The main outcome measures were the distribution of the dye within the vitreous cavity and the retinal sensitivity in the MH patients of the two groups by microperimetry. The visco-BBG was injected over the retina where the ILM was intended to be peeled, and it stained the ILM in all cases. It did not disperse throughout the vitreous cavity or into the subretinal space. The BSS-BBG dispersed throughout the vitreous cavity, and its distribution was difficult to control. The two solutions did not stain the epiretinal membranes or any residual posterior hyaloid membrane. The difference in the retinal sensitivity between the two patients with MH of two groups was not significant. No complications were found in the visco-BBG group, although an accidental retinal perforation was found in one eye of the BSS-BBG group. Transmission electron microscopy confirmed that the membrane peeled was the ILM. Visco-BBG can be a useful method to assist macular surgery and can overcome some of the disadvantages of conventional BBG solutions dissolved in BSS.


Preoperative angiotensin-converting enzyme inhibitors and angiotensin receptor blocker use and acute kidney injury in patients undergoing cardiac surgery.
Using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) the morning of surgery may lead to 'functional' postoperative acute kidney injury (AKI), measured by an abrupt increase in serum creatinine. Whether the same is true for 'structural' AKI, measured with new urinary biomarkers, is unknown. The TRIBE-AKI study was a prospective cohort study of 1594 adults undergoing cardiac surgery at six hospitals between July 2007 and December 2010. We classified the degree of exposure to ACEi/ARB into three categories: 'none' (no exposure prior to surgery), 'held' (on chronic ACEi/ARB but held on the morning of surgery) or 'continued' (on chronic ACEi/ARB and taken the morning of surgery). The co-primary outcomes were 'functional' AKI based upon changes in pre- to postoperative serum creatinine, and 'structural AKI', based upon peak postoperative levels of four urinary biomarkers of kidney injury. Across the three levels (none, held and continued) of ACEi/ARB exposure there was a graded increase in functional AKI, as defined by AKI stage 1 or worse; (31, 34 and 42%, P for trend 0.03) and by percentage change in serum creatinine from pre- to postoperative (25, 26 and 30%, P for trend 0.03). In contrast, there were no differences in structural AKI across the strata of ACEi/ARB exposure, as assessed by four structural AKI biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18 or liver-fatty acid-binding protein). Preoperative ACEi/ARB usage was associated with functional but not structural acute kidney injury. As AKI from ACEi/ARB in this setting is unclear, interventional studies testing different strategies of perioperative ACEi/ARB use are warranted.


Unruptured intracranial aneurysm follow-up and treatment after morphological change is safe: observational study and systematic review.
The management of small unruptured incidentally discovered intracranial aneurysms (SUIAs) is still controversial. The aim of this study is to assess the safety of a management protocol of SUIAs, where selected cases with SUIAs are observed and secured only if signs of instability (growth) are documented. A prospective consecutive cohort of 292 patients (2006-2014) and 368 SUIAs (anterior circulation aneurysms (ACs) smaller than 7 mm and posterior circulation aneurysms smaller than 4 mm without previous subarachnoid haemorrhage) was observed (mean follow-up time of 3.2 years and 1177.6 aneurysm years). Factors associated with aneurysm growth were systematically reviewed from the literature. The aneurysm growth probability was 2.6±0.1% per year. The rate of unexpected aneurysm rupture before treatment was 0.24% per year (95% CI 0.17% to 2.40%). The calculated rate of aneurysm rupture after growth was 6.3% per aneurysm-year (95% CI 1% to 22%). Aneurysms located in the posterior circulation and aneurysms with lobulation were more likely to grow. Females or patients suffering hypertension were more likely to have an aneurysm growing. The probability of aneurysms growth increased with the size of the dome and was proportional to the number of aneurysms diagnosed in a patient. It is safe to observe patients diagnosed with SUIAs using periodic imaging. Intervention to secure the aneurysm should be performed after growth is observed.


Chimeric O1K foot-and-mouth disease virus with SAT2 outer capsid as an FMD vaccine candidate.
Foot-and-mouth disease virus (FMDV) is highly contagious and infects cloven-hoofed domestic livestock leading to foot-and-mouth disease (FMD). FMD outbreaks have severe economic impact due to production losses and associated control measures. FMDV is found as seven distinct serotypes, but there are numerous subtypes within each serotype, and effective vaccines must match the subtypes circulating in the field. In addition, the O and Southern African Territories (SAT) serotypes, are relatively more thermolabile and their viral capsids readily dissociate into non-immunogenic pentameric subunits, which can compromise the effectiveness of FMD vaccines. Here we report the construction of a chimeric clone between the SAT2 and O serotypes, designed to have SAT2 antigenicity. Characterisation of the chimeric virus showed growth kinetics equal to that of the wild type SAT2 virus with better thermostability, attributable to changes in the VP4 structural protein. Sequence and structural analyses confirmed that no changes from SAT2 were present elsewhere in the capsid as a consequence of the VP4 changes. Following exposure to an elevated temperature the thermostable SAT2-O1K chimera induced higher neutralizing-antibody titres in comparison to wild type SAT2 virus.


A mouse model of human primitive neuroectodermal tumors resulting from microenvironmentally-driven malignant transformation of orthotopically transplanted radial glial cells.
There is growing evidence and a consensus in the field that most pediatric brain tumors originate from stem cells, of which radial glial cells constitute a subtype. Here we show that orthotopic transplantation of human radial glial (RG) cells to the subventricular zone of the 3rd ventricle--but not to other transplantation sites--of the brain in immunocompromised NOD-SCID mice, gives rise to tumors that have the hallmarks of CNS primitive neuroectodermal tumors (PNETs). The resulting mouse model strikingly recapitulates the phenotype of PNETs. Importantly, the observed tumorigenic transformation was accompanied by aspects of an epithelial to mesenchymal transition (EMT)-like process. It is also noteworthy that the tumors are highly invasive, and that they effectively recruit mouse endothelial cells for angiogenesis. These results are significant for several reasons. First, they show that malignant transformation of radial glial cells can occur in the absence of specific mutations or inherited genomic alterations. Second, they demonstrate that the same radial glial cells may either give rise to brain tumors or differentiate normally depending upon the microenvironment of the specific region of the brain to which the cells are transplanted. In addition to providing a prospect for drug screening and development of new therapeutic strategies, the resulting mouse model of PNETs offers an unprecedented opportunity to identify the cancer driving molecular alterations and the microenvironmental factors that are responsible for committing otherwise normal radial glial cells to a malignant phenotype.


Understanding racial differences in computerized neurocognitive test performance and symptom-reporting to deliver culturally competent patient-centered care for sport-related concussion.
This study examined neurocognitive performance and symptoms between concussed Black and White collegiate athletes at baseline, post-injury, and change from baseline to post-injury. The Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) was used to measure neurocognitive performance and four concussion symptom clusters for 235 concussed collegiate athletes. Between-groups differences were documented at baseline and post-injury, along with change in scores for sex/race, and sport/race groups, using ANOVAs. Baseline scores, and days-to-post-test were covariates in post-injury comparisons. Symptom endorsement by race was evaluated using chi-square analyses. At baseline, group comparisons by race and sex showed that Black male/female athletes scored lower on reaction time (RT; p = .008), White females scored higher on verbal memory (VerbMem; p = .001), Black females scored lower on visual motor processing speed (VMS; p = .001), and Black football athletes scored slower/poorer on RT (p = .001) and VMS (p = .006). Post-injury, Black males scored lower on visual memory (VisMem; p = .005) and VMS (p = .002), and Black football athletes scored slower on VMS (p = .005), whereas White non-football athletes scored higher on VerbMem (p = .002) and reported fewer symptoms. Significant time-by-sport/race interactions were found for VerbMem (p < .001), VisMem (p < .001) and reported symptoms. With respect to post-injury symptom scores/endorsement, Black athletes scored significantly higher for physical (p = .01) and sleep (p = .01) symptoms. These findings drive the conversation of how subjective measures of symptoms, and objective clinical concussion measures, may relate to the concussion recovery process and providing a culturally competent clinical management approach for diverse patients.


ABC for people with HIV: responses to sexual behaviour recommendations among people receiving antiretroviral therapy in Jinja, Uganda.
People living with HIV who are taking antiretroviral therapy (ART) are increasingly involved in 'positive prevention' initiatives. These are generally oriented to promoting abstinence, 'being faithful' (partner reduction) and condom use (ABC). We conducted a longitudinal qualitative study with people living with HIV using ART, who were provided with adherence education and counselling support by a Ugandan non-governmental organisation, The AIDS Support Organisation (TASO). Forty people were selected sequentially as they started ART, stratified by sex, ART delivery mode (clinic- or home-based) and HIV progression stage (early or advanced) and interviewed at enrollment and at 3, 6, 18 and 30 months. At initiation of ART, participants agreed to follow TASO's positive-living recommendations. Initially poor health prevented sexual activity. As health improved, participants prioritised resuming economic production and support for their children. With further improvements, sexual desire resurfaced and people in relationships cemented these via sex. The findings highlight the limitations of HIV prevention based on medical care/personal counselling. As ART leads to health improvements, social norms, economic needs and sexual desires increasingly influence sexual behaviour. Positive prevention interventions need to seek to modify normative and economic influences on sexual behaviour, as well as to provide alternatives to condoms.


PTH prevents the adverse effects of focal radiation on bone architecture in young rats.
Radiation therapy is a common treatment regimen for cancer patients. However, its adverse effects on the neighboring bone could lead to fractures with a great impact on quality of life. The underlying mechanism is still elusive and there is no preventive or curative solution for this bone loss. Parathyroid hormone (PTH) is a current therapy for osteoporosis that has potent anabolic effects on bone. In this study, we found that focal radiation from frequent scans of the right tibiae in 1-month-old rats by micro-computed tomography severely decreased trabecular bone mass and deteriorated bone structure. Interestingly, PTH daily injections remarkably improved trabecular bone in the radiated tibiae with increases in trabecular number, thickness, connectivity, structure model index and stiffness, and a decrease in trabecular separation. Histomorphometric analysis revealed that radiation mainly decreased the number of osteoblasts and impaired their mineralization activity but had little effects on osteoclasts. PTH reversed these adverse effects and greatly increased bone formation to a similar level in both radiated and non-radiated bones. Furthermore, PTH protects bone marrow mesenchymal stem cells from radiation-induced damage, including a decrease in number and an increase in adipogenic differentiation. While radiation generated the same amount of free radicals in the bone marrow of vehicle-treated and PTH-treated animals, the percentage of apoptotic bone marrow cells was significantly attenuated in the PTH group. Taken together, our data demonstrate a radioprotective effect of PTH on bone structure and bone marrow and shed new light on a possible clinical application of anabolic treatment in radiotherapy.


Brain expression of the calcineurin inhibitor RCAN1 (Adapt78).
RCAN1 (Adapt78) is an endogenous inhibitor of calcineurin, an important intracellular phosphatase that mediates many cellular responses to calcium. RCAN1 is expressed in multiple organs, especially heart, skeletal muscle and brain. In brain, it is thought to be important due to its strong expression, developmental regulation, abundance of target protein (calcineurin), and putative links to multiple brain-related disorders. Surprisingly, however, few studies have examined RCAN1 protein expression here. This has led to some confusion in the field over the exact nature and cell-type expression of isoform 4, the more studied of the two major RCAN1 protein isoforms, in brain. Here we characterize RCAN1 brain isoforms in more detail by assessing their size and distribution under conditions of calcium elevation, a hallmark of the isoform 4 response, and using rodent models to allow for more expanded analyses. We find that the 25-29kDa version of this protein, reported in many non-brain studies, is indeed also present in neurons, and most observable after calcium induction. We also observe that expression of isoform 4 is not specific to neurons, as both microglia and astrocyte cells in culture exhibit a strong induction of isoform 4 protein following calcium stress that is not observable in non-stressed tissue sections. Isoform 1 expression is also observable in a primary glial cell-type (rat microglia). Finally, our observations confirm previous reports of low or non-detectable constitutive isoform expression in non-stressed glia, and of a larger sized, RCAN1 antibody-interacting species. These studies extend and complement previous studies on RCAN isoforms toward better understanding the role of RCAN1 in brain function and as a potential new target for treating calcineurin-related brain disorders.


Consumer-providers of care for adult clients of statutory mental health services.
In mental health services, the past several decades has seen a slow but steady trend towards employment of past or present consumers of the service to work alongside mental health professionals in providing services. However the effects of this employment on clients (service recipients) and services has remained unclear.We conducted a systematic review of randomised trials assessing the effects of employing consumers of mental health services as providers of statutory mental health services to clients. In this review this role is called 'consumer-provider' and the term 'statutory mental health services' refers to public services, those required by statute or law, or public services involving statutory duties. The consumer-provider's role can encompass peer support, coaching, advocacy, case management or outreach, crisis worker or assertive community treatment worker, or providing social support programmes. To assess the effects of employing current or past adult consumers of mental health services as providers of statutory mental health services. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 3), MEDLINE (OvidSP) (1950 to March 2012), EMBASE (OvidSP) (1988 to March 2012), PsycINFO (OvidSP) (1806 to March 2012), CINAHL (EBSCOhost) (1981 to March 2009), Current Contents (OvidSP) (1993 to March 2012), and reference lists of relevant articles. Randomised controlled trials of current or past consumers of mental health services employed as providers ('consumer-providers') in statutory mental health services, comparing either: 1) consumers versus professionals employed to do the same role within a mental health service, or 2) mental health services with and without consumer-providers as an adjunct to the service. Two review authors independently selected studies and extracted data. We contacted trialists for additional information. We conducted analyses using a random-effects model, pooling studies that measured the same outcome to provide a summary estimate of the effect across studies. We describe findings for each outcome in the text of the review with considerations of the potential impact of bias and the clinical importance of results, with input from a clinical expert. We included 11 randomised controlled trials involving 2796 people. The quality of these studies was moderate to low, with most of the studies at unclear risk of bias in terms of random sequence generation and allocation concealment, and high risk of bias for blinded outcome assessment and selective outcome reporting.Five trials involving 581 people compared consumer-providers to professionals in similar roles within mental health services (case management roles (4 trials), facilitating group therapy (1 trial)). There were no significant differences in client quality of life (mean difference (MD) -0.30, 95% confidence interval (CI) -0.80 to 0.20); depression (data not pooled), general mental health symptoms (standardised mean difference (SMD) -0.24, 95% CI -0.52 to 0.05); client satisfaction with treatment (SMD -0.22, 95% CI -0.69 to 0.25), client or professional ratings of client-manager relationship; use of mental health services, hospital admissions and length of stay; or attrition (risk ratio 0.80, 95% CI 0.58 to 1.09) between mental health teams involving consumer-providers or professional staff in similar roles.There was a small reduction in crisis and emergency service use for clients receiving care involving consumer-providers (SMD -0.34 (95%CI -0.60 to -0.07). Past or present consumers who provided mental health services did so differently than professionals; they spent more time face-to-face with clients, and less time in the office, on the telephone, with clients' friends and family, or at provider agencies.Six trials involving 2215 people compared mental health services with or without the addition of consumer-providers. There were no significant differences in psychosocial outcomes (quality of life, empowerment, function, social relations), client satisfaction with service provision (SMD 0.76, 95% CI -0.59 to 2.10) and with staff (SMD 0.18, 95% CI -0.43 to 0.79), attendance rates (SMD 0.52 (95% CI -0.07 to 1.11), hospital admissions and length of stay, or attrition (risk ratio 1.29, 95% CI 0.72 to 2.31) between groups with consumer-providers as an adjunct to professional-led care and those receiving usual care from health professionals alone. One study found a small difference favouring the intervention group for both client and staff ratings of clients' needs having been met, although detection bias may have affected the latter. None of the six studies in this comparison reported client mental health outcomes.No studies in either comparison group reported data on adverse outcomes for clients, or the financial costs of service provision. Involving consumer-providers in mental health teams results in psychosocial, mental health symptom and service use outcomes for clients that were no better or worse than those achieved by professionals employed in similar roles, particularly for case management services.There is low quality evidence that involving consumer-providers in mental health teams results in a small reduction in clients' use of crisis or emergency services. The nature of the consumer-providers' involvement differs compared to professionals, as do the resources required to support their involvement. The overall quality of the evidence is moderate to low. There is no evidence of harm associated with involving consumer-providers in mental health teams.Future randomised controlled trials of consumer-providers in mental health services should minimise bias through the use of adequate randomisation and concealment of allocation, blinding of outcome assessment where possible, the comprehensive reporting of outcome data, and the avoidance of contamination between treatment groups. Researchers should adhere to SPIRIT and CONSORT reporting standards for clinical trials.Future trials should further evaluate standardised measures of clients' mental health, adverse outcomes for clients, the potential benefits and harms to the consumer-providers themselves (including need to return to treatment), and the financial costs of the intervention. They should utilise consistent, validated measurement tools and include a clear description of the consumer-provider role (eg specific tasks, responsibilities and expected deliverables of the role) and relevant training for the role so that it can be readily implemented. The weight of evidence being strongly based in the United States, future research should be located in diverse settings including in low- and middle-income countries.


Quantitation of house dust mites and house dust mite allergens in the microenvironment of dogs.
To quantitate the density of Dermatophagoides farinae and D pteronyssinus and concentrations of house dust mite (HDM) allergens (Der f 1, Der p 1, and Group 2 allergens) in the indoor microenvironment of dogs. 50 homes in Columbus, Ohio. In each home, samples of dust were collected from 3 locations in which dogs spent most time. Whenever possible, the species of mites collected was identified. Mite density (mites/g of dust) was assessed, and allergen concentrations were assayed by standardized ELISAs. Relative humidity and temperature in each home were monitored during a 5-day period. Characteristics of homes and sample sources were evaluated. Dust samples from all 50 homes contained > or = 1 HDM allergen; Der f 1 and Der p 1 were detected in 100 and 74% of homes, respectively. Fifteen homes had HDMs; compared with D pteronyssinus, D farinae was found more commonly (14/15 homes) and at a higher density. Basements, homes without central air-conditioning, and dog beds that were > or = 1 year old had high HDM allergen concentrations. Homes with > or = 2 microg of Der f 1 or Group 2 allergens/g of dust or > or = 100 mites/g of dust were significantly more likely to have a maximum relative humidity > or = 75%. Results indicated the presence of HDMs and HDM allergens in the specific microenvironment of dogs in homes. Factors associated with high levels of exposure were identified, which may be associated with increased risk for sensitization and development of atopic diseases.


Long-path supercontinuum absorption spectroscopy for measurement of atmospheric constituents.
A supercontinuum source has been proposed as a new tool for measurement of minor species concentrations on long paths through the atmosphere. The present work describes results from recent experiments that demonstrate the potential for Differential Absorption Spectroscopy (DAS) and Spectral Pattern Recognition Differential Absorption Lidar (SPR-DIAL) measurements utilizing a supercontinuum source. As an initial example of this measurement approach, the results include the quantification of water vapor concentration through indoor and outdoor path absorption measurements using a collimated supercontinuum source. Experimental spectra are compared with equivalent simulations from MODTRAN??? versions 4 and 5 to examine the water vapor band between 1300 and 1500 nm to demonstrate the feasibility of the approach.


Diversity and functional analysis of bacterial communities associated with natural hydrocarbon seeps in acidic soils at Rainbow Springs, Yellowstone National Park.
In this paper we describe the bacterial communities associated with natural hydrocarbon seeps in nonthermal soils at Rainbow Springs, Yellowstone National Park. Soil chemical analysis revealed high sulfate concentrations and low pH values (pH 2.8 to 3.8), which are characteristic of acid-sulfate geothermal activity. The hydrocarbon composition of the seep soils consisted almost entirely of saturated, acyclic alkanes (e.g., n-alkanes with chain lengths of C15 to C30, as well as branched alkanes, predominately pristane and phytane). Bacterial populations present in the seep soils were phylogenetically characterized by 16S rRNA gene clone library analysis. The majority of the sequences recovered (>75%) were related to sequences of heterotrophic acidophilic bacteria, including Acidisphaera spp. and Acidiphilium spp. of the alpha-Proteobacteria. Clones related to the iron- and sulfur-oxidizing chemolithotroph Acidithiobacillus spp. were also recovered from one of the seep soils. Hydrocarbon-amended soil-sand mixtures were established to examine [14C]hexadecane mineralization and corresponding changes in the bacterial populations using denaturing gradient gel electrophoresis (DGGE) of 16S rRNA gene fragments. Approximately 50% of the [14C]hexadecane added was recovered as 14CO2 during an 80-day incubation, and this was accompanied by detection of heterotrophic acidophile-related sequences as dominant DGGE bands. An alkane-degrading isolate was cultivated, whose 16S rRNA gene sequence was identical to the sequence of a dominant DGGE band in the soil-sand mixture, as well as the clone sequence recovered most frequently from the original soil. This and the presence of an alkB gene homolog in this isolate confirmed the alkane degradation capability of one population indigenous to acidic hydrocarbon seep soils.


The evolving epidemiology of Clostridium difficile infection in Canadian hospitals during a postepidemic period (2009-2015).
The clinical and molecular epidemiology of health care-associated Clostridium difficile infection in nonepidemic settings across Canada has evolved since the first report of the virulent North American pulsed-field gel electrophoresis type 1 (NAP1) strain more than 15 years ago. The objective of this national, multicentre study was to describe the evolving epidemiology and molecular characteristics of health care-associated C. difficile infection in Canada during a post-NAP1-epidemic period, particularly patient outcomes associated with the NAP1 strain. Adult inpatients with C. difficile infection were prospectively identified, using a standard definition, between 2009 and 2015 through the Canadian Nosocomial Infection Surveillance Program (CNISP), a network of 64 acute care hospitals. Patient demographic characteristics, severity of infection and outcomes were reviewed. Molecular testing was performed on isolates, and strain types were analyzed against outcomes and epidemiologic trends. Over a 7-year period, 20 623 adult patients admitted to hospital with health care-associated C. difficile infection were reported to CNISP, and microbiological data were available for 2690 patients. From 2009 to 2015, the national rate of health care-associated C. difficile infection decreased from 5.9 to 4.3 per 10 000 patient-days. NAP1 remained the dominant strain type, but infection with this strain has significantly decreased over time, followed by an increasing trend of infection with NAP4 and NAP11 strains. The NAP1 strain was significantly associated with a higher rate of death attributable to C. difficile infection compared with non-NAP1 strains (odds ratio 1.91, 95% confidence interval [CI] 1.29-2.82). Isolates were universally susceptible to metronidazole; one was nonsusceptible to vancomycin. The proportion of NAP1 strains within individual centres predicted their rates of health care-associated C. difficile infection; for every 10% increase in the proportion of NAP1 strains, the rate of health care-associated C. difficile infection increased by 3.3% (95% CI 1.7%-4.9%). Rates of health care-associated C. difficile infection have decreased across Canada. In nonepidemic settings, NAP4 has emerged as a common strain type, but NAP1, although decreasing, continues to be the predominant circulating strain and remains significantly associated with higher attributable mortality.


Genomic alterations in head and neck squamous cell carcinoma determined by cancer gene-targeted sequencing.
To determine genomic alterations in head and neck squamous cell carcinoma (HNSCC) using formalin-fixed, paraffin-embedded (FFPE) tumors obtained through routine clinical practice, selected cancer-related genes were evaluated and compared with alterations seen in frozen tumors obtained through research studies. DNA samples obtained from 252 FFPE HNSCC were analyzed using next-generation sequencing-based (NGS) clinical assay to determine sequence and copy number variations in 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. Human papillomavirus (HPV) status was determined by presence of the HPV DNA sequence in all samples and corroborated with high-risk HPV in situ hybridization (ISH) and p16 immunohistochemical (IHC) staining in a subset of tumors. Sequencing data from 399 frozen tumors in The Cancer Genome Atlas and University of Chicago public datasets were analyzed for comparison. Among 252 FFPE HNSCC, 84 (33%) were HPV positive and 168 (67%) were HPV negative by sequencing. A subset of 40 tumors with HPV ISH and p16 IHC results showed complete concordance with NGS-derived HPV status. The most common genes with genomic alterations were PIK3CA and PTEN in HPV-positive tumors and TP53 and CDKN2A/B in HPV-negative tumors. In the pathway analysis, the PI3K pathway in HPV-positive tumors and DNA repair-p53 and cell cycle pathways in HPV-negative tumors were frequently altered. The HPV-positive oropharynx and HPV-positive nasal cavity/paranasal sinus carcinoma shared similar mutational profiles. The genomic profile of FFPE HNSCC tumors obtained through routine clinical practice is comparable with frozen tumors studied in research setting, demonstrating the feasibility of comprehensive genomic profiling in a clinical setting. However, the clinical significance of these genomic alterations requires further investigation through application of these genomic profiles as integral biomarkers in clinical trials.


The Relationship Between Vitamin D and Telomere/Telomerase: A Comprehensive Review.
Telomeres are repetitive nucleotide sequences that together with the associated sheltrin complex protect the ends of chromosomes and maintain genomic stability. Evidences from various organisms suggests that several factors influence telomere length regulation, such as telomere binding proteins, telomere capping proteins, telomerase, and DNA replication enzymes. Recent studies suggest that micronutrients, such as vitamin D, folate and vitamin B12, are involved in telomere biology and cellular aging. In particular, vitamin D is important for a range of vital cellular processes including cellular differentiation, proliferation and apoptosis. As a result of the multiple functions of vitamin D it has been speculated that vitamin D might play a role in telomere biology and genomic stability. In this study, our main goal is investigating the relationship between telomerase enzyme and vitamin D. Findings of this study suggest that higher vitamin D concentrations, which are easily modifiable through nutritional supplementation, are associated with longer LTL, which underscores the potentially beneficial effects of this hormone on aging and age-related diseases. Vitamin D may reduce telomere shortening through anti-inflammatory and anti-cell proliferation mechanisms. Significant Low levels of telomerase activity create short telomeres, which in turn signal exit from the cell cycle resulting in cell senescence and apoptosis. In follow-up examination, the patients who remained vitamin D deficient tended to have shorter telomeres than those patients whose 25-hydroxyvitamin D levels were depleted. Increasing 25-hydroxyvitamin D levels in patients with SLE may be beneficial in maintaining telomere length and preventing cellular aging. Moreover, anti-telomere antibody levels may be a promising biomarker of SLE status and disease activity.


Mechanism by which the IFN-beta enhanceosome activates transcription.
We demonstrate that in contrast to previous findings by using simple synthetic promoters or activators, the natural IFN-beta enhanceosome activates transcription by causing a dramatic increase of the rate by which preinitiation complexes assemble at the promoter. This effect totally depends on the recruitment of the CBP-PolII holoenzyme by the enhanceosome, because its depletion from the extract decelerates the rate of transcription. However, addition of the CBP-PolII holoenzyme back to these extracts fully restores the speed by which the enhanceosome activates transcription. Strikingly, preincubation of the enhanceosome with the CBP-RNA PolII holoenzyme complex results in instant assembly of preinitiation complexes. In contrast, individual IFN-beta gene activators function solely by increasing the number of functional preinitiation complexes and not the rate of their assembly. Thus, fast recruitment of the CBP-RNA PolII holoenzyme complex is critical for the rapid activation of IFN-beta gene expression by virus infection.


Living Conditions and the Mental Health and Well-being of Refugees: Evidence from a Large-Scale German Survey.
Refugees are at an increased risk of mental health problems and low subjective well-being. Living circumstances in the host country are thought to play a vital role in shaping these health outcomes, which, in turn, are prerequisites for successful integration. Using data from a representative survey of 4325 adult refugees who arrived in Germany between 2013 and 2016, we investigated how different living conditions, especially those subject to integration policies, are associated with psychological distress and life satisfaction using linear regression models. Our findings show that an uncertain legal status, separation from family, and living in refugee housing facilities are related to higher levels of distress and decreased life satisfaction. Being employed, contact to members of the host society, and better host country language skills, by contrast, are related to reduced distress and higher levels of life satisfaction. These associations should inform decision making in a highly contested policy area.


Development and Testing of a Communication Intervention to Improve Chronic Pain Management in Primary Care: A Pilot Randomized Clinical Trial.
Effective communication skills are essential for optimally managing chronic pain and opioids. This exploratory, sequential mixed methods study tested the effect of a novel framework designed to improve pain-related communication and outcomes. Study 1 developed a novel 5-step framework for helping primary care clinicians discuss chronic pain and opioids with patients. Study 2 pilot tested an intervention for teaching this framework using standardized patient instructors-actors trained to portray patients and provide immediate clinician feedback-deployed during regular clinic hours. Primary care physicians were randomized to receive either the intervention or pain management recommendations from the Centers for Disease Control and Prevention. Primary outcomes were pain-related interference at 2 months and clinician use of targeted communication skills (coded from transcripts of audio-recorded visits); secondary outcomes were pain intensity at 2 months, clinician self-efficacy for communicating about chronic pain, patient experience, and clinician-reported visit difficulty. We enrolled 47 primary care physicians from 2 academic teaching clinics and recorded visits with 48 patients taking opioids for chronic pain who had an appointment scheduled with an enrolled physician. The intervention was not associated with significant changes in primary or secondary outcomes other than clinician self-efficacy, which was significantly greater in the intervention group. This study developed a novel framework and intervention for teaching clinician pain-related communications skills. Although the intervention showed promise, more intensive or multicomponent interventions may be needed to have a significant impact on clinicians' pain-related communication and pain outcomes.


Atrial fibrillation management: a prospective survey in ESC member countries: the Euro Heart Survey on Atrial Fibrillation.
To describe atrial fibrillation (AF) management in member countries of the European Society of Cardiology (ESC) and to verify cardiology practices against guidelines. Among 182 hospitals in 35 countries, 5333 ambulant and hospitalized AF patients were enrolled, in 2003 and 2004. AF was primary or secondary diagnosis, and was confirmed on ECG in the preceding 12 months. Clinical type of AF was reported to be first detected in 978, paroxysmal in 1517, persistent in 1167, and permanent in 1547 patients. Concomitant diseases were present in 90% of all patients, causing risk factors for stroke to be also highly prevalent (86%). As many as 69% of patients were symptomatic at the time of the survey; among asymptomatic patients, 54% were previously experienced symptoms. Oral anticoagulation was prescribed in 67 and 49% of eligible and ineligible patients, respectively. A rhythm control strategy was applied in 67% of currently symptomatic patients and in 44% of patients who never experienced symptoms. This survey provides a unique snapshot of current AF management in ESC member countries. Discordance between guidelines and practice was found regarding several issues on stroke prevention and antiarrhythmic therapy.


Nutritional programming of coenzyme Q: potential for prevention and intervention?
Low birth weight and rapid postnatal growth increases risk of cardiovascular-disease (CVD); however, underlying mechanisms are poorly understood. Previously, we demonstrated that rats exposed to a low-protein diet in utero that underwent postnatal catch-up growth (recuperated) have a programmed deficit in cardiac coenzyme Q (CoQ) that was associated with accelerated cardiac aging. It is unknown whether this deficit occurs in all tissues, including those that are clinically accessible. We investigated whether aortic and white blood cell (WBC) CoQ is programmed by suboptimal early nutrition and whether postweaning dietary supplementation with CoQ could prevent programmed accelerated aging. Recuperated male rats had reduced aortic CoQ [22 d (35±8.4%; P<0.05); 12 m (53±8.8%; P<0.05)], accelerated aortic telomere shortening (P<0.01), increased DNA damage (79±13% increase in nei-endonucleaseVIII-like-1), increased oxidative stress (458±67% increase in NAPDH-oxidase-4; P<0.001), and decreased mitochondrial complex II-III activity (P<0.05). Postweaning dietary supplementation with CoQ prevented these detrimental programming effects. Recuperated WBCs also had reduced CoQ (74±5.8%; P<0.05). Notably, WBC CoQ levels correlated with aortic telomere-length (P<0.0001) suggesting its potential as a diagnostic marker of vascular aging. We conclude that early intervention with CoQ in at-risk individuals may be a cost-effective and safe way of reducing the global burden of CVDs.


Atmospheric lifetimes of long-lived halogenated species.
The atmospheric lifetimes of the fluorinated gases CF(4), C(2)F(6), c-C(4)F(8), (CF(3))(2)c-C(4)F(6), C(5)F(12), C(6)F(14), C(2)F(5)Cl, C(2)F(4)C(12), CF(3)Cl, and SF(6) are of concern because of the effects that these long-lived compounds acting as greenhouse gases can have on global climate. The possible atmospheric loss processes of these gases were assessed by determining the rate coefficients for the reactions of these gases with O((1)D), H, and OH and the absorption cross sections at 121.6 nanometers in the laboratory and using these data as input to a two-dimensional atmospheric model. The lifetimes of all the studied perfluoro compounds are >2000 years, and those of CF(3)Cl, CF(3)CF(2)Cl, and CF(2)ClCF(2)Cl are >300 years. If released into the atmosphere, these molecules will accumulate and their effects will persist for centuries or millennia.


Development of an analytical method to quantify pharmaceuticals in fish tissues by liquid chromatography-tandem mass spectrometry detection and application to environmental samples.
A sensitive multiresidue method was developed to quantify 35 pharmaceuticals and 28 metabolites/transformation products (TPs) in fish liver, fish fillet and fish plasma via LC-MS/MS. The method was designed to cover a broad range of substance polarities. This objective was realized by using non-discriminating sample clean-ups including separation technique based on size exclusion, namely restricted access media (RAM) chromatography. This universal clean-up allows for an easy integration of further organic micropollutants into the analytical method. Limits of quantification (LOQ) ranged from 0.05 to 5.5 ng/mL in fish plasma, from 0.1 to 19 ng/g d.w. (dry weight) in fish fillet and from 0.46 to 48 ng/g d.w. in fish liver. The method was applied for the analysis of fillets and livers of breams from the rivers Rhine and Saar, the Teltow Canal as well as carps kept in fish monitoring ponds fed by effluent from municipal wastewater treatment plants. This allowed for the first detection of 17 analytes including 10 metabolites/TPs such as gabapentin lactam and norlidocaine in fish tissues. These results highlight the importance of including metabolites and transformation products of pharmaceuticals in fish monitoring campaigns and further investigating their potential effects.


[Hyperbolic growth of marine and continental biodiversity through the phanerozoic and community evolution].
Among diverse models that are used to describe and interpret the changes in global biodiversity through the Phanerozoic, the exponential and logistic models (traditionally used in population biology) are the most popular. As we have recently demonstrated (Markov, Korotayev, 2007), the growth of the Phanerozoic marine biodiversity at genus level correlates better with the hyperbolic model (widely used in demography and macrosociology). Here we show that the hyperbolic model is also applicable to the Phanerozoic continental biota at genus and family levels, and to the marine biota at species, genus, and family levels. There are many common features in the evolutionary dynamics of the marine and continental biotas that imply similarity and common nature of the factors and mechanisms underlying the hyperbolic growth. Both marine and continental biotas are characterized by continuous growth of the mean longevity of taxa, by decreasing extinction and origination rates, by similar pattern of replacement of dominant groups, by stepwise accumulation of evolutionary stable, adaptable and "physiologically buffered" taxa with effective mechanisms of parental care, protection of early developmental stages, etc. At the beginning of the development of continental biota, the observed taxonomic diversity was substantially lower than that predicted by the hyperbolic model. We suggest that this is due, firstly, to the fact that, during the earliest stages of the continental biota evolution, the groups that are not preserved in the fossil record (such as soil bacteria, unicellular algae, lichens, etc.) played a fundamental role, and secondly, to the fact that the continental biota initially formed as a marginal portion of the marine biota, rather than a separate system. The hyperbolic dynamics is most prominent when both marine and continental biotas are considered together. This fact can be interpreted as a proof of the integrated nature of the biosphere. In the macrosociological models, the hyperbolic pattern of the world population growth arises from a non-linear second-order positive feedback between the demographic growth and technological development (more people - more potential inventors - faster technological growth - the carrying capacity of the Earth grows faster - faster population growth - more people - more potential inventors, and so on). Based on the analogy with macrosociological models and diverse paleontological data, we suggest that the hyperbolic character of biodiversity growth can be similarly accounted for by a non-linear second-order positive feedback between the diversity growth and community structure complexity. The feedback can work via two parallel mechanisms: 1) decreasing extinction rate (more taxa- higher alpha diversity, or mean number of taxa in a community - communities become more complex and stable - extinction rate decreases - more taxa, and so on) and 2) increasing origination rate (new taxa facilitate niche construction; newly formed niches can be occupied by the next "generation" of taxa). The latter possibility makes the mechanisms underlying the hyperbolic growth of biodiversity and human population even more similar, because the total ecospace of the biota is analogous to the "carrying capacity of the Earth" in demography. As far as new species can increase ecospace and facilitate opportunities for additional species entering the community, they are analogous to the "inventors" of the demographic models whose inventions increase the carrying capacity of the Earth. The hyperbolic growth of the Phanerozoic biodiverstiy suggests that "cooperative" interactions between taxa can play an important role in evolution, along with generally accepted competitive interactions. Due to this "cooperation", the evolution of biodiversity acquires some features of a self-accelerating process. Macroevolutionary "cooperation" reveals itself in: 1) increasing stability of communities that arises from alpha diversity growth; 2) ability of species to facilitate opportunities for additional species entering the community.


Effect of hydralazine on the mesenteric vasculature of hypertensive rats.
To test whether structural alterations observed in the mesenteric vasculature of Wistar-Kyoto spontaneously hypertensive rats (SHR) were dependent on the presence of hypertension, male SHR and Wistar-Kyoto normotensive (WKY) rats were treated in utero and postnatally with hydralazine up to 28 weeks of age. Treated SHR, WKY, and untreated WKY rats had comparable blood pressures that were less than those of untreated SHR. Treatment altered the dimensions of the superior mesenteric, intermediate-sized, and small arteries of the mesenteric vasculature. In the case of the superior mesenteric artery and intermediate vessels, hydralazine treatment increased the lumen and medial cross-sectional areas of the arteries in WKY rats and slightly decreased both parameters in SHR. Within the small arteries, treatment significantly increased the lumen size in SHR but not WKY rats and had no significant effect on the media of the vessels. Despite the above alterations, the media-to-lumen cross-sectional area ratios remained significantly elevated in SHR over WKY rats in both the treated and control groups of animals within all classes of arteries. The results indicate that there is an inherent increase in the quantity of media surrounding the arteries of SHR when compared with WKY rats that cannot be abolished by normalizing the blood pressure in utero and postnatally with hydralazine treatment. In SHR, such changes persist not only in arteries that exhibit an increase in the media-to-lumen ratio before hypertension but also in the superior mesenteric artery in which an increase in the ratio occurs after hypertension development.


Genetic studies in familial ankylosing spondylitis susceptibility.
To define the genetic basis of susceptibility to ankylosing spondylitis (AS), especially non-major histocompatibility complex (MHC) genes. The study group comprised 244 affected sibling pairs from 180 pedigrees of primarily European ancestry. Sibling pairs were concordant for AS by the modified New York criteria and had available sacroiliac radiographs. The subjects were genotyped for 400 markers in ABI PRISM linkage map MD-10 and for 17 additional markers on chromosomes 6p, 6q, and 11q (including HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles). Two-point and multipoint nonparametric linkage (NPL) analyses were conducted using the NPL statistic and 1-parameter allele-sharing model logarithm of odds (LOD) scores, calculated using the Allele-Sharing Model (ASM) computer program. Linkage of the MHC region was supported by both 2-point and multipoint analyses, with the strongest peak (45.90 cM) in the MHC at the HLA-DRB1 locus (NPL score 8.720, ASM LOD score 20.49; P = 6.8 x 10(-20) for 2-point analysis). A second region was found to have positive linkage at the q arm of chromosome 6 (D6S441) in 2-point analysis; this was supported by a 39.13-cM region (135.58-174.71 cM) in multipoint analysis, with the smallest P value (4.2 x 10(-3)) at 166.39 cM. A third region was found on chromosome 11q, with the strongest evidence for linkage for D11S4094 at 123 cM (NPL score 2.235, ASM LOD score 1.939) and, on transmission disequilibrium test analysis, D11S4090 at 105.74 cM (P = 6.2 x 10(-5)). Linkage in this area was supported by multipoint analysis, spanning 22.19 cM continuously from 101.68 cM to 123.87 cM, with the strongest peak at 112.33 cM (P = 0.014); this was confirmed by subsequent fine mapping studies. Thus, this genome-wide scan implicates, in addition to the MHC, regions outside the MHC in AS susceptibility, especially on chromosomes 6q and 11q.


Cortical neuronal mechanisms of sleep homeostasis.
The longer we are awake, the deeper is our subsequent sleep. On the other hand, the shorter and more fragmented is our sleep, the more difficult it is for us to maintain wakefulness and stable cognitive performance the next day. This relationship between wakefulness and subsequent sleep becomes especially apparent after sleep deprivation or during chronic sleep restriction, which is experienced by millions of people in our society, as well as in multiple neurological, respiratory and other chronic diseases. Invariably, poor sleep leads to fatigue, sleepiness, marked cognitive deficits and impaired mood. The crucial question is what happens to the brain after a period of being awake or asleep, and where in the brain and why do these changes occur. This review summarizes information about neurophysiological substrates of sleep homeostatic processes at the cellular and network levels. It is suggested that sensory, behavioral and cognitive deficits after sleep deprivation resulting from the imbalance between local and global neuronal interactions can be reversed only by physiological sleep.


Detection of koi herpesvirus (KHV) in healthy cyprinid seed stock.
Koi herpesvirus (KHV) disease is a lethal disease in common carp, an important food fish in Asian countries, the seed of which is used in restocking programs for freshwater fishery management. We inspected apparently healthy seed stock of common carp Cyprinus carpio L. and Siberian crucian carp Carassius auratus for the presence of KHV using PCR-based diagnostic tests as a part of a stock enhancement program from 2009 to 2010 in Korea. Consequently, KHV was detected from 24 of 232 inspections with yearly detection percentages of 5.2% in 2009 and 15.5% in 2010 using PCR primer sets for TK or SphI-5 as recommended by the OIE Manual of Diagnostic Tests for Aquatic Animals. Results indicate that the SphI-5 primer set was slightly more sensitive than the TK primer set, as shown by a higher detection rate. To determine the genotype of the KHV strains detected in this study, ORF40-specific PCR amplification was conducted, and the PCR products from 6 samples showed 100% nucleotide sequence identity with a Japanese strain (GenBank accession number AP008984) but not with US (DG657948) and Israeli strains (DG177346). This report conclusively demonstrated the presence of KHV in externally healthy seed of common carp and Siberian crucian carp, indicating a possible risk that subclinically infected seed stock can be released with a potential threat to wild populations.


Control of blood pressure in Scotland: the rule of halves.
Audit of detection, treatment, and control of hypertension in adults in Scotland. Cross sectional survey with random population sampling. General practice centres in 22 Scottish districts. 5123 Men and 5236 women aged 40-59 in the Scottish heart health study, randomly selected from 22 districts throughout Scotland, of whom 1262 men and 1061 women had hypertension (defined as receiving antihypertensive treatment or with blood pressure above defined cut off points). Hypertension (assessed by standardised recording, questionnaire on diagnosis, and antihypertensive drug treatment) according to criteria of the World Health Organisation (receiving antihypertensive treatment or blood pressure greater than or equal to 160/95 mm Hg, or both) and to modified criteria of the British Hypertension Society. In half the men with blood pressure greater than or equal to 160/95 mm Hg hypertension was undetected (670/1262, 53%), in half of those in whom it had been detected it was untreated (250/592, 42%), and in half of those receiving treatment it was not controlled (172/342, 50%). In women the numbers were: 486/1061, 46%; 188/575, 33%; and 155/387, 40% respectively. Assessment of blood pressure according to the British Hypertension Society's recommendations showed an improvement, but in only a quarter of men and 42% of women was hypertension detected and treated satisfactorily (142/561, 215/514 respectively). The detection and control of hypertension in Scotland is unsatisfactory, affecting management of this and other conditions, such as high blood cholesterol concentration, whose measurement is opportunistic and selective and depends on recognition of other risk factors.


Chromatin interaction analysis reveals changes in small chromosome and telomere clustering between epithelial and breast cancer cells.
Higher-order chromatin structure is often perturbed in cancer and other pathological states. Although several genetic and epigenetic differences have been charted between normal and breast cancer tissues, changes in higher-order chromatin organization during tumorigenesis have not been fully explored. To probe the differences in higher-order chromatin structure between mammary epithelial and breast cancer cells, we performed Hi-C analysis on MCF-10A mammary epithelial and MCF-7 breast cancer cell lines. Our studies reveal that the small, gene-rich chromosomes chr16 through chr22 in the MCF-7 breast cancer genome display decreased interaction frequency with each other compared to the inter-chromosomal interaction frequency in the MCF-10A epithelial cells. Interestingly, this finding is associated with a higher occurrence of open compartments on chr16-22 in MCF-7 cells. Pathway analysis of the MCF-7 up-regulated genes located in altered compartment regions on chr16-22 reveals pathways related to repression of WNT signaling. There are also differences in intra-chromosomal interactions between the cell lines; telomeric and sub-telomeric regions in the MCF-10A cells display more frequent interactions than are observed in the MCF-7 cells. We show evidence of an intricate relationship between chromosomal organization and gene expression between epithelial and breast cancer cells. Importantly, this work provides a genome-wide view of higher-order chromatin dynamics and a resource for studying higher-order chromatin interactions in two cell lines commonly used to study the progression of breast cancer.


The structural and optical properties of GaSb/InGaAs type-II quantum dots grown on InP (100) substrate.
We have investigated the structural and optical properties of type-II GaSb/InGaAs quantum dots [QDs] grown on InP (100) substrate by molecular beam epitaxy. Rectangular-shaped GaSb QDs were well developed and no nanodash-like structures which could be easily found in the InAs/InP QD system were formed. Low-temperature photoluminescence spectra show there are two peaks centered at 0.75eV and 0.76ev. The low-energy peak blueshifted with increasing excitation power is identified as the indirect transition from the InGaAs conduction band to the GaSb hole level (type-II), and the high-energy peak is identified as the direct transition (type-I) of GaSb QDs. This material system shows a promising application on quantum-dot infrared detectors and quantum-dot field-effect transistor.


Unilateral nasal polyposis: clinical presentation and pathology.
The aim of this study is to determine the clinical presentation and pathology of unilateral nasal polyposis (UNP). Retrospective chart review. A retrospective analysis was completed on 301 consecutive patients with nasal polyposis that underwent functional endoscopic sinus surgery from 1995 to 2004. Of the charts reviewed, 46 patients were identified with UNP. In this group, there were 28 males and 18 females with a mean age at presentation of 34.85 years. Pathologic diagnosis was not available for 2 patients, so there were 44 UNP patient records for analysis. Presenting symptoms, surgical findings, and pathology were analyzed. All 44 patients underwent surgical management for their symptoms, and specimens were sent for pathologic evaluation. There were 17 cases of chronic rhinosinusitis, 15 of allergic fungal sinusitis, 7 of inverting papilloma, 2 of squamous cell carcinoma, 1 of esthesioneuroblastoma, 1 of mucocele, and 1 of human papilloma virus polyp-type papilloma. The only presenting symptom that correlated with the presence of inverted papilloma or neoplastic process in our patients with UNP was epistaxis. Chronic rhinosinusitis, allergic fungal sinusitis, inverting papilloma, and other neoplasms account for most UNP cases and must be considered when a patient presents with symptoms of unilateral polyps. A careful history and endoscopic examination play a key role in identifying possible disease processes and proper management.


Host- and tissue-specific pathogenic traits of Staphylococcus aureus.
Comparative genomics were used to assess genetic differences between Staphylococcus aureus strains derived from infected animals versus colonized or infected humans. A total of 77 veterinary isolates were genetically characterized by high-throughput amplified fragment length polymorphism (AFLP). Bacterial genotypes were introduced in a large AFLP database containing similar information for 1,056 human S. aureus strains. All S. aureus strains isolated from animals in close contact with humans (e.g., pet animals) were predominantly classified in one of the five main clusters of the AFLP database (cluster I). In essence, mastitis-associated strains from animals were categorized separately (cluster IVa) and cosegregated with bacteremia-associated strains from humans. Distribution of only 2 out of 10 different virulence genes differed across the clusters. The gene encoding the toxic shock syndrome protein (tst) was more often encountered among veterinary strains (P < 0.0001) and even more in the mastitis-related strains (P<0.0001) compared to human isolate results. The gene encoding the collagen binding protein (cna) was rarely detected among invasive human strains. The virulence potential, as indicated by the number of virulence genes per strain, did not differ significantly between the human- and animal-related strains. Our data show that invasive infections in pets and humans are usually due to S. aureus strains with the same genetic background. Mastitis-associated S. aureus isolated in diverse farm animal species form a distinct genetic cluster, characterized by an overrepresentation of the toxic shock syndrome toxin superantigen-encoding gene.


Dynamics of fMRI patterns reflect sub-second activation sequences and reveal replay in human visual cortex.
Neural computations are often fast and anatomically localized. Yet, investigating such computations in humans is challenging because non-invasive methods have either high temporal or spatial resolution, but not both. Of particular relevance, fast neural replay is known to occur throughout the brain in a coordinated fashion about which little is known. We develop a multivariate analysis method for functional magnetic resonance imaging that makes it possible to study sequentially activated neural patterns separated by less than 100 ms with precise spatial resolution. Human participants viewed five images individually and sequentially with speeds up to 32 ms between items. Probabilistic pattern classifiers were trained on activation patterns in visual and ventrotemporal cortex during individual image trials. Applied to sequence trials, probabilistic classifier time courses allow the detection of neural representations and their order. Order detection remains possible at speeds up to 32 ms between items (plus 100 ms per item). The frequency spectrum of the sequentiality metric distinguishes between sub- versus supra-second sequences. Importantly, applied to resting-state data our method reveals fast replay of task-related stimuli in visual cortex. This indicates that non-hippocampal replay occurs even after tasks without memory requirements and shows that our method can be used to detect such spontaneously occurring replay.


Personality and gonadal development as sources of individual variation in response to GnRH challenge in female great tits.
Seasonal timing of reproduction is a key life-history trait, but we know little about the mechanisms underlying individual variation in female endocrine profiles associated with reproduction. In birds, 17β-oestradiol is a key reproductive hormone that links brain neuroendocrine mechanisms, involved in information processing and decision-making, to downstream mechanisms in the liver, where egg-yolk is produced. Here, we test, using a simulated induction of the reproductive system through a Gonadotropin-Releasing Hormone (GnRH) challenge, whether the ovary of pre-breeding female great tits responds to brain stimulation by increasing oestradiol. We also assess how this response is modified by individual-specific traits like age, ovarian follicle size, and personality, using females from lines artificially selected for divergent levels of exploratory behaviour. We show that a GnRH injection leads to a rapid increase in circulating concentrations of oestradiol, but responses varied among individuals. Females with more developed ovarian follicles showed stronger responses and females from lines selected for fast exploratory behaviour showed stronger increases compared to females from the slow line, indicating a heritable component. This study shows that the response of the ovary to reproductive stimulation from the brain greatly varies among individuals and that this variation can be attributed to several commonly measured individual traits, which sheds light on the mechanisms shaping heritable endocrine phenotypes.


Assessing learning progress and quality of teaching in large groups of students.
The classic tool of assessing learning progress are written tests and assignments. In large groups of students the workload often does not allow in depth evaluation during the course. Thus our aim was to modify the course to include active learning methods and student centered teaching. We changed the course structure only slightly and established new assessment methods like minute papers, short tests, mini-projects and a group project at the end of the semester. The focus was to monitor the learning progress during the course so that problematic issues could be addressed immediately. The year before the changes 26.76 % of the class failed the course with a grade average of 3.66 (Pass grade is 4.0/30 % of achievable marks). After introducing student centered teaching, only 14 % of students failed the course and the average grade was 3.01. Grades were also distributed more evenly with more students achieving better results. We have shown that even in large groups of students with > 100 participants student centered and active learning is possible. Although it requires a great work overhead on the behalf of the teaching staff, the quality of teaching and the motivation of the students is increased leading to a better learning environment.


Quantification of visual orienting responses to coherent form and motion in typically developing children aged 0-12 years.
Brain damage or brain development disorders can affect (the maturation of) visual processing functions, such as form and motion detection. The aim of our study was to investigate visual orienting responses of children to a coherent form and motion stimulus as a measure for maturation of visual information processing. The 213 typically developing children aged 0-12 years included in this study were shown a 100% coherent form and motion expansion stimulus on a remote eye tracking monitor. Orienting eye movements were quantified in terms of ocular motor reaction time to fixation (RTF). Children were divided in age groups, and their performance was compared to 30 healthy adults with a mean age of 24.49 years (SD 3.62 years). The RTF values of coherent form in children up to six years old were significantly higher compared to the adult group (P < 0.05, Dunnett post-hoc test). For motion, mature levels were reached at eight years old. RTF values depended on stimulus type (F(1,168) = 240.8, P < 0.001) and age (F(11,168) = 25.8, P < 0.001), and there was a significant age by stimulus type interaction (F(11,168) = 2.2, P < 0.05). Remote eye tracking may provide objective insight into the maturation of visual information processing of coherent form and motion without complex instructions or active cooperation. The quantification of typical visual orienting behavior in childhood may be used as a reference for children with brain dysfunction.


Implication of Leptin-Signaling Proteins and Epstein-Barr Virus in Gastric Carcinomas.
We investigated the clinicopathological implications of leptin-signaling proteins and Epstein-Barr virus (EBV)-infection status in gastric carcinomas. Immunohistochemistry for leptin signalling-related proteins (leptin, leptin-receptor, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha), and in situ hybridization for EBV-encoded small RNAs was performed in 343 cases of gastric carcinomas. The siRNA against leptin-receptor was transfected into three stomach cancer cell lines, and western blot for caspase 3 was performed. The TNM stage was a prognostic factor in all 343 patients, and was negatively correlated with expression of leptin, pSTAT3, ERK, pAkt, mTOR and HIF-1 alpha (P < 0.05). Leptin-receptor expression was correlated with poor survival in 207 patients of the advanced gastric cancer (AGC) subgroup, 139 of the Lauren diffuse group, and in 160 patients with lymph node metastasis (P < 0.05, respectively). Additionally, in stomach cancer cells, cleaved caspase 3 level increased by leptin-receptor inhibition, that is, apoptosis increased. Interestingly, EBV-positive AGC (n = 29) tended to show better survival of patients than EBV-negative AGC (n = 178) (P = 0.06). pAkt expression was related with a good survival of 32 patients (9%) in the EBV-positive subgroup, but was not an independent prognostic factor. Among, leptin signaling-related proteins, expressions of leptin-receptor and mTOR were different between EBV-positive subgroup and EBV-negative subgroup (P < 0.05, respectively). In conclusion, leptin-signaling proteins and EBV status show different significance on patient survival, according to subsets of gastric carcinomas. The leptin-receptor may predict poor patient prognosis in the AGC, Lauren diffuse and lymph node metastasis subgroups, while EBV-positive status can show a good prognosis in the AGC. Each leptin signaling-related protein may be differently involved in carcinogenesis of EBV-negative and EBV-positive subsets.


Transdermal bio-identical progesterone cream as hormonal treatment for osteoarthritis.
Osteoarthritis (OA) is a condition found worldwide, is strongly associated with aging and is the most common type of arthritis. Because of its effect on ambulation and mobility, it has significant functional impact and is associated with considerable medical costs. Because of the aging of the society and the obesity epidemic, the burden of OA can be expected to increase over the next 20 years. Although OA has been regarded primarily as a non-inflammatory arthropathy, symptoms of local inflammation and synovitis are present in many patients and have been observed and even in the absence of classical inflammation, which is characterized by infiltration of neutrophils and macrophages into joint tissue, elevated levels of inflammatory cytokines have been measured in OA synovial fluid. Although the cartilage lesion is present at sites remote from synovium, the fibroblast- and macrophage-like synovial cells, as well as the chondrocytes itself, are potential sources of cytokines that could induce chondrocytes to synthesize and secrete cartilage-degrading proteases, cytokines, and other inflammatory mediators. The bio-identical progesterone shows its anti-inflammatory effects in OA by suppressing gene expressions in the production of inflammatory cytokines through the negative interaction between nuclear transcription factor and the progesterone receptor and/or the progesterone-induced increase of nuclear transcription factor inhibition in the nucleus. The bio-identical progesterone may indirectly regulate bone remodeling and may also play a role in the development and maintenance of cartilage. This review will discuss about transdermal bio-identical progesterone cream as suggested hormonal treatment of OA, based on its pathogenic process.


A neutral model of transcriptome evolution.
Microarray technologies allow the identification of large numbers of expression differences within and between species. Although environmental and physiological stimuli are clearly responsible for changes in the expression levels of many genes, it is not known whether the majority of changes of gene expression fixed during evolution between species and between various tissues within a species are caused by Darwinian selection or by stochastic processes. We find the following: (1) expression differences between species accumulate approximately linearly with time; (2) gene expression variation among individuals within a species correlates positively with expression divergence between species; (3) rates of expression divergence between species do not differ significantly between intact genes and expressed pseudogenes; (4) expression differences between brain regions within a species have accumulated approximately linearly with time since these regions emerged during evolution. These results suggest that the majority of expression differences observed between species are selectively neutral or nearly neutral and likely to be of little or no functional significance. Therefore, the identification of gene expression differences between species fixed by selection should be based on null hypotheses assuming functional neutrality. Furthermore, it may be possible to apply a molecular clock based on expression differences to infer the evolutionary history of tissues.


Testing the accuracy of Bedek et al's new models based on 1-to-7 mandibular teeth for age estimation in 7-15 year old south Indian children.
Age estimation significantly contributes to forensic medicine and law enforcement in Indonesia. However, lateral cephalometric radiographs of cervical vertebrae have not been used to estimate age in the Indonesian population. This study developed a formula to estimate the skeletal age of cervical vertebrae using multiple linear regression analyses, estimating the dental age and evaluating the agreement between cervical vertebrae skeletal-chronological, dental-chronological, and cervical vertebrae skeletal-dental ages. Several anatomical parameters were measured to obtain cervical vertebrae ratios from 100 lateral cephalometric radiographs, and followed by the calculation of dental tooth crown index data from 100 panoramic radiographs of subjects 9-18 years old. The Bland-Altman plot of cervical vertebrae skeletal and dental ages showed a mean difference of -0.094 ± 1.52 years, with upper and lower limits of 2.882 and -3.070 years, respectively. The means of the cervical vertebrae skeletal, dental, and chronological ages were 13.97 (2.67), 14.06 (2.45), and 13.97 (2.97), respectively. The mean differences between cervical vertebrae skeletal-chronological and dental-chronological ages were 0.566 (2.26) and 4.005 (2.07), respectively. Furthermore, a validation trial (group 2, n = 10, three males and seven females) was conducted to test the accuracy of the cervical vertebrae skeletal age estimation formula using consecutive sampling. The age range was 9-11 years. Cervical vertebrae skeletal age showed a better agreement with chronological age than did dental age.


Comparison of two pre-anaesthetic medetomidine doses in isoflurane anaesthetized sheep.
To compare the sedative, anaesthetic-sparing and arterial blood-gas effects of two medetomidine (MED) doses used as pre-anaesthetic medication in sheep undergoing experimental orthopaedic surgery. Randomized, prospective, controlled experimental trial. Twenty-four adult, non-pregnant, female sheep of various breeds, weighing 53.9 +/- 7.3 kg (mean +/- SD). All animals underwent experimental tibial osteotomy. Group 0 (n = 8) received 0.9% NaCl, group L (low dose) (n = 8) received 5 microg kg(-1) MED and group H (high dose) (n = 8) received 10 microg kg(-1) MED by intramuscular (IM) injection 30 minutes before induction of anaesthesia with intravenous (IV) propofol 1% and maintenance with isoflurane delivered in oxygen. The propofol doses required for induction and endtidal isoflurane concentrations (F(E')ISO) required to maintain anaesthesia were recorded. Heart and respiratory rates and rectal temperature were determined before and 30 minutes after administration of the test substance. The degree of sedation before induction of anaesthesia was assessed using a numerical rating scale. Arterial blood pressure, heart rate, respiratory rate, FE'ISO, end-tidal CO2 (FE'CO2) and inspired O2 (FIO2) concentration were recorded every 10 minutes during anaesthesia. Arterial blood gas values were determined 10 minutes after induction of anaesthesia and every 30 minutes thereafter. Changes over time and differences between groups were examined by analysis of variance (anova) for repeated measures followed by Bonferroni-adjusted t-tests for effects over time. Both MED doses produced mild sedation. The dose of propofol for induction of anaesthesia decreased in a dose-dependent manner: mean (+/-SE) values for group 0 were 4.7 (+/-0.4) mg kg(-1), for group L, 3.2 (+/-0.4) mg kg(-1) and for group H, 2.3 (+/-0.3) mg kg(-1)). The mean (+/-SE) FE'ISO required to maintain anaesthesia was 30% lower in both MED groups [group L: 0.96 (+/-0.07) %; group H: 1.06 (+/-0.09) %] compared with control group values [(1.54 +/- 0.17) %]. Heart rates were constantly higher in the control group with a tendency towards lower arterial blood pressures when compared with the MED groups. Respiratory rates and PaCO2 were similar in all groups while PaO2 increased during anaesthesia with no significant difference between groups. In group H, one animal developed a transient hypoxaemia: PaO2 was 7.4 kPa (55.7 mmHg) 40 minutes after induction of anaesthesia. Arterial pH values and bicarbonate concentrations were higher in the MED groups at all time points. Intramuscular MED doses of 5 and 10 microg kg(-1) reduced the propofol and isoflurane requirements for induction and maintenance of anaesthesia respectively. Cardiovascular variables and blood gas measurements remained stable over the course of anaesthesia but hypoxaemia developed in one of 16 sheep receiving MED.


Predicting the location of human perirhinal cortex, Brodmann's area 35, from MRI.
The perirhinal cortex (Brodmann's area 35) is a multimodal area that is important for normal memory function. Specifically, perirhinal cortex is involved in the detection of novel objects and manifests neurofibrillary tangles in Alzheimer's disease very early in disease progression. We scanned ex vivo brain hemispheres at standard resolution (1 mm × 1 mm × 1 mm) to construct pial/white matter surfaces in FreeSurfer and scanned again at high resolution (120 μm × 120 μm × 120 μm) to determine cortical architectural boundaries. After labeling perirhinal area 35 in the high resolution images, we mapped the high resolution labels to the surface models to localize area 35 in fourteen cases. We validated the area boundaries determined using histological Nissl staining. To test the accuracy of the probabilistic mapping, we measured the Hausdorff distance between the predicted and true labels and found that the median Hausdorff distance was 4.0mm for the left hemispheres (n=7) and 3.2mm for the right hemispheres (n=7) across subjects. To show the utility of perirhinal localization, we mapped our labels to a subset of the Alzheimer's Disease Neuroimaging Initiative dataset and found decreased cortical thickness measures in mild cognitive impairment and Alzheimer's disease compared to controls in the predicted perirhinal area 35. Our ex vivo probabilistic mapping of the perirhinal cortex provides histologically validated, automated and accurate labeling of architectonic regions in the medial temporal lobe, and facilitates the analysis of atrophic changes in a large dataset for earlier detection and diagnosis.


Novel radiopaque ultrahigh molecular weight polyethylene sublaminar wires in a growth-guidance system for the treatment of early-onset scoliosis: feasibility in a large animal study.
In vivo analysis in an ovine model. To evaluate the feasibility of radiopaque ultrahigh molecular weight polyethylene (UHMWPE) sublaminar wires in a growth-guidance spinal system by assessing stability, biocompatibility, and growth potential. Several growth-guidance systems have been developed for the treatment of early-onset scoliosis. The use of gliding pedicle screws and metal sublaminar wires during these procedures can cause metal-on-metal debris formation and neurological deficits. Novel radiopaque UHMWPE wires are introduced to safely facilitate longitudinal growth and provide stability in a growth-guidance system for early-onset scoliosis. Twelve immature sheep received posterior segmental spinal instrumentation; pedicle screws were inserted at L5 and radiopaque UHMWPE (bismuth trioxide) wires were passed sublaminarly at each level between L3 and T12 and fixed to dual cobalt-chromium rods. Four age-matched animals that were not operated were evaluated to serve as a control group. Radiographs were obtained to measure growth of the instrumented segment. After 24 weeks, the animals were killed and the spines were harvested for histological evaluation and high-resolution peripheral quantitative computed tomographic analysis. No neurological deficits occurred and all instrumentation remained stable. One animal died from an unknown cause. Substantial growth occurred in the instrumented segments (L5-T11) in the intervention group (27 ± 2 mm), which was not significantly different to the control group, (30 ± 4 mm, P = 0.42). High-resolution peripheral quantitative computed tomographic analysis clearly showed safe routing and fixation of the UHMWPE wires and instrumentation. Despite the noted growth, ectopic bone formation with the formation of bony bridges was observed in all animals. Histology revealed no evidence of chronic inflammation or wear debris. This study shows the first results of radiopaque UHMWPE sublaminar wires as part of a growth-guidance spinal system. UHMWPE sublaminar wires facilitated near-normal longitudinal spinal growth. All instrumentation remained stable throughout follow-up; no wire breakage or loosening occurred and no adverse local-tissue response to these wires was observed. N/A.


Investigating the Presence of Interattack Astrocyte Damage in Neuromyelitis Optica Spectrum Disorder: Longitudinal Analysis of Serum Glial Fibrillary Acidic Protein.
Information on subclinical astrocyte damage can provide further insight into neuromyelitis optica spectrum disorder (NMOSD) pathophysiology and disease-monitoring strategies. To investigate whether astrocyte and neuroaxonal damage occurs during interattack periods in individuals with NMOSD through longitudinal measurement of serum glial fibrillary acidic protein (sGFAP) and neurofilament light chain (sNfL) at multiple time points. sGFAP and sNfL levels were measured in 187 serum samples from 20 participants with NMOSD treated with rituximab (median follow-up: 24 months) and 19 age-/sex-matched healthy controls using a highly sensitive single-molecule array assay. From the NMOSD cohort of National Cancer Center, Korea, 14 clinically stable participants were randomly selected for focused investigation of interattack periods, and 6 participants with clinical attacks despite treatment were enrolled for attack-related measurements. Significant elevations of sGFAP levels were observed in all clinical attacks, and 95% (19/20) of patients showed reduction of sGFAP levels below the cutoff value (3 SDs above mean levels in age-/sex-matched healthy controls) within 3 months of their clinical attacks. The sGFAP levels were consistently low during interattack periods in 90% (17/19) of patients whose sGFAP levels returned to below the cutoff value. Changes in sNfL levels were similar to but slower than those in sGFAP levels. Subclinical astrocyte damage represented by increasing sGFAP levels rarely occurred during interattack periods in individuals with NMOSD; however, a certain degree of astrocyte damage did occur at the time of clinical attacks without exception, but it was not evident within 3 months of the attack.


The prevalence of sensorineural symptoms attributable to hand-transmitted vibration in Great Britain: a national postal survey.
Exposure to hand-transmitted vibration (HTV) can cause sensorineural symptoms in the upper limb, but its impact has not previously been assessed in the general population. To investigate, we mailed a questionnaire about exposures to HTV, finger blanching and sensory symptoms (numbness or tingling) in the upper limbs to a population sample comprising 21,201 working-aged men and women selected at random from the age-sex registers of 34 British general practices, and a further 993 randomly selected from the pay records of the armed services. Associations were explored using multiple logistic regression models to adjust for confounding, with the resultant odds ratios converted into prevalence rate ratios (PRs). Of 12,907 respondents, 2,607 (20.2%) reported sensory symptoms in the upper limb during the past week. Sensory symptoms were more prevalent in those with blanching, and were commonly associated with exposure to HTV, especially in men. In comparison with men who had never been exposed to HTV, the PR in men exposed both at work and in leisure was 2.2 (95% CI 1.9-2.4). Associations were found even in those who had never blanched. Sensorineural symptoms in the upper limbs are common. HTV is an important risk factor for such complaints in the general population.


Clinical and visual outcomes of patients with uveitis in the mid-Atlantic United States.
To report the clinical outcomes of uveitis patients at the University of Virginia. Retrospective, observational study of uveitis patients seen at the University of Virginia from 1984 to 2014. Parametric and nonparametric methods were used to analyze the change in best-corrected visual acuity (BCVA) in relation to demographics, diagnoses, management, and complications. The study included 644 eyes of 491 patients. Patients with mild visual loss (logMAR <0.4) at presentation were younger than those with severe visual loss (SVL, logMAR >1.0) (P=0.002). Females were more likely to have mild visual loss as compared to males (P=0.025). Median overall BCVA was logMAR 0.18 at initial and final presentation (P=1.00). Vision loss at diagnosis was a predictor for moderate visual loss (MVL, logMAR 0.4 to <1.0) to SVL at last follow-up (P<0.001). Eyes with ocular hypertension were positively associated with MVL and SVL as compared to normotensive eyes (1.89 times at baseline, 2.62 times at last follow-up). Median BCVA was 0.18 logMAR for the anterior uveitis (AU) and 0.48 logMAR for the non-AU patients (P<0.001). AU patients were less likely to have SVL than non-AU group (P<0.001). AU group received local corticosteroids more frequently and systemic corticosteroids less commonly than non-AU patients (P<0.001). AU patients with MVL to SVL were more likely to have ophthalmic surgery (cataract, glaucoma or pars plana vitrectomy [PPV]) than those without MVL or SVL (P<0.001). Non-AU patients with MVL to SVL were more likely to have PPV than those without MVL or SVL (P=0.001). Mean overall BCVA remained stable. Favorable visual results were associated with younger age, female gender, and AU. Poor visual prognosis was concomitant with SVL at presentation and ocular hypertension. Ocular surgery (cataract extraction and glaucoma filtration) was more frequently performed for AU patients with MVL to SVL than those AU patients who did not experience moderate to SVL. PPV was commonly performed for both AU and non-AU patients with MVL to SVL.


Identification of a member of the catalase multigene family on wheat chromosome 7A associated with flour b* colour and biological significance of allelic variation.
Carotenoids (especially lutein) are known to be the pigment source for flour b* colour in bread wheat. Flour b* colour variation is controlled by a quantitative trait locus (QTL) on wheat chromosome 7AL and one gene from the carotenoid pathway, phytoene synthase, was functionally associated with the QTL on 7AL in some, but not all, wheat genotypes. A SNP marker within a sequence similar to catalase (Cat3-A1snp) derived from full-length (FL) cDNA (AK332460), however, was consistently associated with the QTL on 7AL and implicated in regulating hydrogen peroxide (H2O2) to control carotenoid accumulation affecting flour b* colour. The number of catalase genes on chromosome 7AL was investigated in this study to identify which gene may be implicated in flour b* variation and two were identified through interrogation of the draft wheat genome survey sequence consisting of five exons and a further two members having eight exons identified through comparative analysis with the single catalase gene on rice chromosome 6, PCR amplification and sequencing. It was evident that the catalase genes on chromosome 7A had duplicated and diverged during evolution relative to its counterpart on rice chromosome 6. The detection of transcripts in seeds, the co-location with Cat3-A1snp marker and maximised alignment of FL-cDNA (AK332460) with cognate genomic sequence indicated that TaCat3-A1 was the member of the catalase gene family associated with flour b* colour variation. Re-sequencing identified three alleles from three wheat varieties, TaCat3-A1a, TaCat3-A1b and TaCat3-A1c, and their predicted protein identified differences in peroxisomal targeting signal tri-peptide domain in the carboxyl terminal end providing new insights into their potential role in regulating cellular H2O2 that contribute to flour b* colour variation.


Cognitive support technologies for people with TBI: current usage and challenges experienced.
We investigated the current use of off-the-shelf cognitive support technologies (CSTs) by individuals with traumatic brain injury (TBI), the challenges they and their caregivers face when using these technologies, the functional areas where support is needed, and their current experience in learning new technologies. We conducted two focus groups with participants with TBI and their caregivers. Focus group interactions were captured using recordings and a court reporter. Transcripts were analyzed qualitatively. We identified three core themes - consumer and caregiver self-reported needs for support, how support is used on a daily basis and consumer and caregiver attitudes towards the use of support by types of support. We also inferred implications for design of CSTs. Individuals with TBI use consumer available technologies to support cognition. The design of most of these devices is not targeted to meet the needs of people with TBI, and they can be challenging to use independently, but individuals and their caregivers still benefit from their use by embedding technology as one type of support within a broader support network that includes personal assistance. People with traumatic brain injury (TBI) are attempting to use a wide range of consumer available technologies to support cognition, although not always successfully. One important role for rehabilitation providers could be helping people with TBI use these technologies with more accuracy and success. People with TBI note that an important element in adopting new technology is good training in its use. Cognitive support technologies (CSTs) are one part of broader network of supports. People with TBI and their caregivers desire independence but do not want to lose the human element that can be provided by a caregiver. New technologies should be implemented with an understanding of an individual's broader support network. Psychosocial aspects of TBI need to be considered when designing and implementing CSTs. In particular, rehabilitation providers need to address the anxiety that many people with TBI experience, including fear about forgetting and their need for early, repeated reminders so they can prepare for upcoming events.


Colonic epithelial expression of ErbB2 is required for postnatal maintenance of the enteric nervous system.
We utilized the Cre-LoxP system to establish erbB2 conditional mutant mice in order to investigate the role of erbB2 in postnatal development of the enteric nervous system. The erbB2/nestin-Cre conditional mutants exhibit retarded growth, distended colons, and premature death, resembling human Hirschsprung's disease. Enteric neurons and glia are present at birth in the colon of erbB2/nestin-Cre mutants; however, a marked loss of multiple classes of enteric neurons and glia occurs by 3 weeks of age. Furthermore, we demonstrate that the requirement for erbB2 in maintaining the enteric nervous system is not cell autonomous, but rather erbB2 signaling in the colonic epithelia is required for the postnatal survival of enteric neurons and glia.


HDAC6-p97/VCP controlled polyubiquitin chain turnover.
HDAC6 is a unique cytoplasmic deacetylase capable of interacting with ubiquitin. Using a combination of biophysical, biochemical and biological approaches, we have characterized the ubiquitin-binding domain of HDAC6, named ZnF-UBP, and investigated its biological functions. These studies show that the three Zn ion-containing HDAC6 ZnF-UBP domain presents the highest known affinity for ubiquitin monomers and mediates the ability of HDAC6 to negatively control the cellular polyubiquitin chain turnover. We further show that HDAC6-interacting chaperone, p97/VCP, dissociates the HDAC6-ubiquitin complexes and counteracts the ability of HDAC6 to promote the accumulation of polyubiquitinated proteins. We propose that a finely tuned balance of HDAC6 and p97/VCP concentrations determines the fate of ubiquitinated misfolded proteins: p97/VCP would promote protein degradation and ubiquitin turnover, whereas HDAC6 would favour the accumulation of ubiquitinated protein aggregates and inclusion body formation.


Associations between political/civic participation and HIV drug injection risk.
Participating in civic activities has been found to be related to positive health outcomes. This study examines associations between injection drug use health variables (sharing paraphernalia, using shooting galleries) and political/civic engagement (identifying with any political party, attention paid to politics and being registered to vote). Participants (N = 162) were recruited at 6 New York City (NYC) methadone programs as part of an HIV intervention (86% male). In the bivariate analysis, being registered to vote and political party identification were related to lower paraphernalia sharing; higher levels of attention paid to politics were associated with lower shooting gallery use. In the multivariate analysis, political party identification was associated with lower paraphernalia sharing and higher levels of attention paid to politics was related to lower shooting gallery use. Findings suggest that maintaining connections with mainstream civic activities can be related to reduced health risks, including HIV risk behaviors. This study contributes to understanding the relationships between involvement in civic/political participation and health, an area in which few studies have been conducted.


Added effect of heat wave on mortality in Seoul, Korea.
A heat wave could increase mortality owing to high temperature. However, little is known about the added (duration) effect of heat wave from the prolonged period of high temperature on mortality and different effect sizes depending on the definition of heat waves and models. A distributed lag non-linear model with a quasi-Poisson distribution was used to evaluate the added effect of heat wave on mortality after adjusting for long-term and intra-seasonal trends and apparent temperature. We evaluated the cumulative relative risk of the added wave effect on mortality on lag days 0-30. The models were constructed using nine definitions of heat wave and two relationships (cubic spline and linear threshold model) between temperature and mortality to leave out the high temperature effect. Further, we performed sensitivity analysis to evaluate the changes in the effect of heat wave on mortality according to the different degrees of freedom for time trend and cubic spline of temperature. We found that heat wave had the added effect from the prolonged period of high temperature on mortality and it was considerable in the aspect of cumulative risk because of the lagged influence. When heat wave was defined with a threshold of 98th percentile temperature and ≥2, 3, and 4 consecutive days, mortality increased by 14.8 % (7.5-22.6, 95 % confidence interval (CI)), 18.1 % (10.8-26.0, 95 % CI), 18.1 % (10.7-25.9, 95 % CI), respectively, in cubic spline model. When it came to the definitions of 90th and 95th percentile, the risk increase in mortality declined to 3.7-5.8 % and 8.6-11.3 %, respectively. This effect was robust to the flexibility of the model for temperature and time trend, while the definitions of a heat wave were critical in estimating its relationship with mortality. This finding could help deepen our understanding and quantifying of the relationship between heat wave and mortality and select an appropriate definition of heat wave and temperature model in the future studies.