Epidemiologic and molecular pathophysiology of chronic opioid dependence and the place of naltrexone extended-release formulations in its clinical management.
Naltrexone implants and depot injections (NI) are a novel form of treatment for opiate dependence (OD). Major questions relate to their absolute and relative efficacy and safety. Opportunely, six recent clinical trial data from several continents have uniformly provided dramatic evidence of the potent, dose-related and highly significant efficacy of NI, with minimal or manageable accompanying toxicity and safety concerns. The opiate-free lifestyle is attained significantly more often with NI adjusted O.R. = 6.00 (95% C.I. 3.86-9.50), P < 10(-10). Other drug use and drug craving are also rapidly reduced. The optimum manner in which to commence NI remains to be established. Of particular relevance is the relative safety of NI compared to the chronic opiate agonists (COA) usually employed, as the long-term toxicity of COA is only just being elucidated. Large population-based studies have found elevated rates of cardiovascular disease, six cancers, liver and respiratory disease, and all-cause mortality in COA. Whilst opiates have been shown to trigger numerous molecular pathways, the most interesting is the demonstration that the opiate morphinan's nucleus binds to the endotoxin groove of the TLR4-MD2 heterodimer. This has the effect of triggering a low grade endotoxaemic-like state, which over time may account for these protean clinical findings, an effect which is reversed by opiate antagonists. This emerging evidence suggests an exciting new treatment paradigm for OD and a corresponding increase in the role of NI in treatment.


Effective noise-suppressed and artifact-reduced reconstruction of SPECT data using a preconditioned alternating projection algorithm.
The authors have recently developed a preconditioned alternating projection algorithm (PAPA) with total variation (TV) regularizer for solving the penalized-likelihood optimization model for single-photon emission computed tomography (SPECT) reconstruction. This algorithm belongs to a novel class of fixed-point proximity methods. The goal of this work is to investigate how PAPA performs while dealing with realistic noisy SPECT data, to compare its performance with more conventional methods, and to address issues with TV artifacts by proposing a novel form of the algorithm invoking high-order TV regularization, denoted as HOTV-PAPA, which has been explored and studied extensively in the present work. Using Monte Carlo methods, the authors simulate noisy SPECT data from two water cylinders; one contains lumpy "warm" background and "hot" lesions of various sizes with Gaussian activity distribution, and the other is a reference cylinder without hot lesions. The authors study the performance of HOTV-PAPA and compare it with PAPA using first-order TV regularization (TV-PAPA), the Panin-Zeng-Gullberg one-step-late method with TV regularization (TV-OSL), and an expectation-maximization algorithm with Gaussian postfilter (GPF-EM). The authors select penalty-weights (hyperparameters) by qualitatively balancing the trade-off between resolution and image noise separately for TV-PAPA and TV-OSL. However, the authors arrived at the same penalty-weight value for both of them. The authors set the first penalty-weight in HOTV-PAPA equal to the optimal penalty-weight found for TV-PAPA. The second penalty-weight needed for HOTV-PAPA is tuned by balancing resolution and the severity of staircase artifacts. The authors adjust the Gaussian postfilter to approximately match the local point spread function of GPF-EM and HOTV-PAPA. The authors examine hot lesion detectability, study local spatial resolution, analyze background noise properties, estimate mean square errors (MSEs), and report the convergence speed and computation time. HOTV-PAPA yields the best signal-to-noise ratio, followed by TV-PAPA and TV-OSL/GPF-EM. The local spatial resolution of HOTV-PAPA is somewhat worse than that of TV-PAPA and TV-OSL. Images reconstructed using HOTV-PAPA have the lowest local noise power spectrum (LNPS) amplitudes, followed by TV-PAPA, TV-OSL, and GPF-EM. The LNPS peak of GPF-EM is shifted toward higher spatial frequencies than those for the three other methods. The PAPA-type methods exhibit much lower ensemble noise, ensemble voxel variance, and image roughness. HOTV-PAPA performs best in these categories. Whereas images reconstructed using both TV-PAPA and TV-OSL are degraded by severe staircase artifacts; HOTV-PAPA substantially reduces such artifacts. It also converges faster than the other three methods and exhibits the lowest overall reconstruction error level, as measured by MSE. For high-noise simulated SPECT data, HOTV-PAPA outperforms TV-PAPA, GPF-EM, and TV-OSL in terms of hot lesion detectability, noise suppression, MSE, and computational efficiency. Unlike TV-PAPA and TV-OSL, HOTV-PAPA does not create sizable staircase artifacts. Moreover, HOTV-PAPA effectively suppresses noise, with only limited loss of local spatial resolution. Of the four methods, HOTV-PAPA shows the best lesion detectability, thanks to its superior noise suppression. HOTV-PAPA shows promise for clinically useful reconstructions of low-dose SPECT data.


Detection of North American orthopoxviruses by real time-PCR.
The prevalence of North American orthopoxviruses in nature is unknown and may be more difficult to ascertain due to wide spread use of vaccinia virus recombinant vaccines in the wild. A real time PCR assay was developed to allow for highly sensitive and specific detection of North American orthopoxvirus DNA in animal tissues and bodily fluids. This method is based on the amplification of a 156 bp sequence within a myristylated protein, highly conserved within the North American orthopoxviruses but distinct from orthologous genes present in other orthopoxviruses. The analytical sensitivity was 1.1 fg for Volepox virus DNA, 1.99 fg for Skunkpox virus DNA, and 6.4 fg for Raccoonpox virus DNA with a 95% confidence interval. Our assay did not cross-react with other orthopoxviruses or ten diverse representatives of the Chordopoxvirinae subfamily. This new assay showed more sensitivity than tissue culture tests, and was capable of differentiating North American orthopoxviruses from other members of Orthopoxvirus. Thus, our assay is a promising tool for highly sensitive and specific detection of North American orthopoxviruses in the United States and abroad.


A randomised controlled trial to improve the role of the general practitioner in cancer rehabilitation: effect on patients' satisfaction with their general practitioners.
To test whether a complex intervention facilitating early cancer rehabilitation by involvement of the general practitioner (GP) soon after diagnosis improves patients' satisfaction with their GPs. A cluster randomised controlled trial. All general practices in Denmark were randomised to an intervention or a control group before the start of the study. Patients included those with cancer who were subsequently allocated to either group based on the randomisation status of their GP. Adult patients with cancer treated for incident cancer at the public regional hospital (Vejle Hospital, Denmark) were included between May 2008 and February 2009. A total of 955 patients registered with 323 practices were included, of which 486 patients were allocated to the intervention group and 469 to the control group. The intervention included a patient interview assessing the need for rehabilitation, improved information from the hospital to GPs including information on the patients' current needs along with information about needs of patients with cancer in general. Further, GPs were encouraged to proactively contact the patients and facilitate the patients' rehabilitation course. 6 months after inclusion of the patient, patient satisfaction with their GP during the last 12 months in five different dimensions of GP care was assessed using the Danish version of the EuroPEP (European Patients Evaluate General Practice Care) questionnaire (DanPEP). 14 months after inclusion, patient satisfaction with the GP regarding the cancer course and GP's satisfaction with own contribution to the patients' rehabilitation course were assessed using ad hoc questions specifically designed for this study. No overall effect of the intervention was observed. Subgroup analysis of the patients with breast cancer showed statistically significant improvement of satisfaction with the GP in two of the five DanPEP dimensions. This complex intervention aiming at improving GPs' services in cancer rehabilitation had no impact on patient satisfaction. ClinicalTrials.gov, registration ID number NCT01021371.


Repetition blindness and the Colavita effect.
People often fail to respond to an auditory target if they have to respond to a visual target presented at the same time, a phenomenon known as the Colavita visual dominance effect. To date, the Colavita effect has only ever been demonstrated in detection tasks in which participants respond to pre-defined visual, auditory, or bimodal audiovisual target stimuli. Here, we tested the Colavita effect when the target was defined by a rule, namely the repetition of any event (a picture, a sound, or both) in simultaneously-presented streams of pictures and sounds. Given previous findings that people are better at detecting auditory repetitions than visual repetitions, we expected that the Colavita visual dominance effect might disappear (or even reverse). Contrary to this prediction, however, visual dominance (i.e., the typical Colavita effect) was observed, with participants still neglecting significantly more auditory events than visual events in response to bimodal targets. The visual dominance for bimodal repetitions was observed despite the fact that participants missed significantly more unimodal visual repetitions than unimodal auditory repetitions. These results therefore extend the Colavita visual dominance effect to a domain where auditory dominance has traditionally been observed. In addition, our results reveal that the Colavita effect occurs at a more abstract, rule-based, level of representation than tested in previous research.


Leaf stable carbon isotope composition reflects transpiration efficiency in Zea mays.
The increasing demand for food production and predicted climate change scenarios highlight the need for improvements in crop sustainability. The efficient use of water will become increasingly important for rain-fed agricultural crops even in fertile regions that have historically received ample precipitation. Improvements in water-use efficiency in Zea mays have been limited, and warrant a renewed effort aided by molecular breeding approaches. Progress has been constrained by the difficulty of measuring water-use in a field environment. The stable carbon isotope composition (δ13 C) of the leaf has been proposed as an integrated signature of carbon fixation with a link to stomatal conductance. However, additional factors affecting leaf δ13 C exist, and a limited number of studies have explored this trait in Z. mays. Here we present an extensive characterization of leaf δ13 C in Z. mays. Significant variation in leaf δ13 C exists across diverse lines of Z. mays, which we show to be heritable across several environments. Furthermore, we examine temporal and spatial variation in leaf δ13 C to determine the optimum sampling time to maximize the use of leaf δ13 C as a trait. Finally, our results demonstrate the relationship between transpiration and leaf δ13 C in the field and the greenhouse. Decreasing transpiration and soil moisture are associated with decreasing leaf δ13 C. Taken together these results outline a strategy for using leaf δ13 C and reveal its usefulness as a measure of transpiration efficiency under well-watered conditions rather than a predictor of performance under drought.


The pelvis: T2-weighted fast spin-echo MR imaging.
Fast spin-echo (SE) T2-weighted magnetic resonance (MR) imaging provides images with highly T2-weighted contrast in substantially reduced imaging times. In a prospective evaluation, fast SE T2-weighted imaging of the pelvis was compared with conventional SE T2-weighted imaging in 30 consecutive patients in whom pelvic pathologic conditions were suspected. Three reviewers independently analyzed the images for (a) overall image quality, (b) pelvic organ definition, (c) conspicuity of pelvic fluid, and (d) conspicuity of pelvic pathologic conditions. Fast SE images were rated superior to conventional SE T2-weighted images in 60% (54 of 90) of the case reviews for overall image quality, in 69% (62 of 90) for pelvic organ definition, in 63% (57 of 90) for conspicuity of pelvic fluid, and in 68% (43 of 63) for conspicuity of pelvic pathologic conditions. The fast SE examinations were typically three to four times faster than conventional SE T2-weighted examinations. No pathologic findings seen on conventional SE T2-weighted images were undetected on fast SE images. Fast SE images may replace conventional SE T2-weighted images in MR imaging of the pelvis.


Housing for People with an Acquired Brain or Spinal Injury: Mapping the Australian Funding Landscape.
This research aimed to synthesize housing supports funded by 20 major insurance-based schemes for Australians with an acquired brain injury (ABI) or spinal cord injury (SCI). Publicly available grey literature (i.e., primary information from respective scheme websites) was systematically reviewed and compared. There were notable differences between the different scheme types (disability vs. workers compensation schemes) and across different States. Collectively, scheme funding was more likely to be focused on housing infrastructure and service delivery, than on tenancy support. Australians who are least likely to benefit from the current funding context are those whose home cannot be reasonably modified, are wanting to build or purchase a new home, do not have suitable, alternative short- or long-term housing options if their current home is not feasible, require support to maintain occupancy of their home or financial assistance to move into a new home, may benefit from case management services, family supports, and assistance animals, and/or cannot afford their rent or home loan repayments. Several interactions, inconsistencies, contradictions, and gaps that warrant further attention were also revealed. This review has highlighted the need for policy makers to provide transparent information about housing entitlements for individuals with ABI or SCI, and their families. A unified, evidence-based framework to guide the funding of housing and housing support services may increase the consistency of interventions available to people with ABI or SCI and, therefore, improve outcomes.


Neuroinflammation and J2 prostaglandins: linking impairment of the ubiquitin-proteasome pathway and mitochondria to neurodegeneration.
The immune response of the CNS is a defense mechanism activated upon injury to initiate repair mechanisms while chronic over-activation of the CNS immune system (termed neuroinflammation) may exacerbate injury. The latter is implicated in a variety of neurological and neurodegenerative disorders such as Alzheimer and Parkinson diseases, amyotrophic lateral sclerosis, multiple sclerosis, traumatic brain injury, HIV dementia, and prion diseases. Cyclooxygenases (COX-1 and COX-2), which are key enzymes in the conversion of arachidonic acid into bioactive prostanoids, play a central role in the inflammatory cascade. J2 prostaglandins are endogenous toxic products of cyclooxygenases, and because their levels are significantly increased upon brain injury, they are actively involved in neuronal dysfunction induced by pro-inflammatory stimuli. In this review, we highlight the mechanisms by which J2 prostaglandins (1) exert their actions, (2) potentially contribute to the transition from acute to chronic inflammation and to the spreading of neuropathology, (3) disturb the ubiquitin-proteasome pathway and mitochondrial function, and (4) contribute to neurodegenerative disorders such as Alzheimer and Parkinson diseases, and amyotrophic lateral sclerosis, as well as stroke, traumatic brain injury (TBI), and demyelination in Krabbe disease. We conclude by discussing the therapeutic potential of targeting the J2 prostaglandin pathway to prevent/delay neurodegeneration associated with neuroinflammation. In this context, we suggest a shift from the traditional view that cyclooxygenases are the most appropriate targets to treat neuroinflammation, to the notion that J2 prostaglandin pathways and other neurotoxic prostaglandins downstream from cyclooxygenases, would offer significant benefits as more effective therapeutic targets to treat chronic neurodegenerative diseases, while minimizing adverse side effects.


Validation of neuroradiologic response assessment in gliomas: measurement by RECIST, two-dimensional, computer-assisted tumor area, and computer-assisted tumor volume methods.
Significant limitations are associated with the use of standard radiographic measurements as indicators of response in glioma therapy trials. The Response Evaluation Criteria in Solid Tumors (RECIST) were recently introduced in an attempt to standardize and simplify assessment of response to treatment in cancer clinical trials. However, their applicability in gliomas has been assessed in only a very small number of patients. Our aim was to validate radiographic response assessment in newly diagnosed glioma patients. Sixty-seven newly diagnosed glioma patients participating in nine North Central Cancer Treatment Group glioma trials were included; 565 MRI scans were analyzed. All scans were performed with the same technique. Kappa statistics were calculated to determine agreement between assessment methods. Cox proportional hazards analyses and time-dependent Cox models were used to assess the association between different measurement methods and overall survival. Results showed agreement between the one-dimensional (1D) and two-dimensional (2D) measurements both for T2 images and for gadolinium-enhanced images. Comparison of duration of response and time to progression as assessed by eight different methods showed similarity in response assessments by 1D, 2D, area, and volume gadolinium measurements. In contrast, time to progression was significantly shorter when assessed by 1D-T2 or 2D-T2 images as compared to area-T2 or volume-T2 images. This set of data indicates that RECIST could be used instead of 2D imaging for response assessment in newly diagnosed glioma trials. Overall, responses as determined by any tumor measurement method did not correlate with patient survival for either enhancing or nonenhancing tumors, although the small number of responders limits definitive conclusions. Time-dependent Cox models demonstrated that, in contrast to the case of nonenhancing tumors, progression as determined by 1D, 2D, area, and volume measurements in gadolinium-enhanced images was predictive of survival of patients with enhancing tumors.


Structural basis for therapeutic inhibition of complement C5.
Activation of complement C5 generates the potent anaphylatoxin C5a and leads to pathogen lysis, inflammation and cell damage. The therapeutic potential of C5 inhibition has been demonstrated by eculizumab, one of the world's most expensive drugs. However, the mechanism of C5 activation by C5 convertases remains elusive, thus limiting development of therapeutics. Here we identify and characterize a new protein family of tick-derived C5 inhibitors. Structures of C5 in complex with the new inhibitors, the phase I and phase II inhibitor OmCI, or an eculizumab Fab reveal three distinct binding sites on C5 that all prevent activation of C5. The positions of the inhibitor-binding sites and the ability of all three C5-inhibitor complexes to competitively inhibit the C5 convertase conflict with earlier steric-inhibition models, thus suggesting that a priming event is needed for activation.


Adjuvant chemotherapy with six cycles of AC regimen versus three cycles of AC regimen followed by three cycles of Paclitaxel in node-positive breast cancer.
Antracycline-Cyclophosphamide (AC) along with Paclitaxel/Docetaxel, either in combination or sequential regimens, is showing superior results than Anthracycline-containing regimens. This study was designed to determine whether adding Paclitaxel to a standard adjuvant chemotherapy regimen AC for breast cancer patients would prolong the time to recurrence and survival. Randomized, prospective, open-labeled, single-institutional study. Fifty stage II breast cancer patients accruing 25 patients in each arm, treated between July 2007 and January 2010, were included in the study. Initial surgical treatment was Modified Radical Mastectomy. Systemic therapy was to have begun within 4-6 weeks of the patient's surgery. In the control arm, all the patients were treated with six cycles of adjuvant chemotherapy with AC regimen repeated at an interval of 3 weeks. For the study arm, the patients received adjuvant chemotherapy with three cycles of AC regimen followed by three cycles of Paclitaxel, repeated at an interval of 3 weeks. All the patients of both the arms received locoregional external beam radiotherapy (EBRT) after the entire course of chemotherapy. All the hormone receptor-positive patients received Tamoxifen. Statistical analysis was performed using the chi-square test and the Kaplan Meier survival analysis with the log-rank (Mantel-Cox) test. Adding Paclitaxel to AC resulted in a statistically significant disease-free survival. The overall survival was also improved significantly. The toxicity profile in both the arms was comparable. In early and node-positive breast cancer, the addition of three cycles of Paclitaxel after completion of three cycles of AC improves the disease-free and overall survival.


Potential for worldwide displacement of fossil-fuel electricity by nuclear energy in three decades based on extrapolation of regional deployment data.
There is an ongoing debate about the deployment rates and composition of alternative energy plans that could feasibly displace fossil fuels globally by mid-century, as required to avoid the more extreme impacts of climate change. Here we demonstrate the potential for a large-scale expansion of global nuclear power to replace fossil-fuel electricity production, based on empirical data from the Swedish and French light water reactor programs of the 1960s to 1990s. Analysis of these historical deployments show that if the world built nuclear power at no more than the per capita rate of these exemplar nations during their national expansion, then coal- and gas-fired electricity could be replaced worldwide in less than a decade. Under more conservative projections that take into account probable constraints and uncertainties such as differing relative economic output across regions, current and past unit construction time and costs, future electricity demand growth forecasts and the retiring of existing aging nuclear plants, our modelling estimates that the global share of fossil-fuel-derived electricity could be replaced within 25-34 years. This would allow the world to meet the most stringent greenhouse-gas mitigation targets.


Are older adults living in more equal counties healthier than older adults living in more unequal counties? A propensity score matching approach.
We assessed the potential contextual effect of income inequality on health by: 1) comparing individuals with similar socioeconomic status (SES) but who reside in counties with different levels of income inequality; and 2) examining whether the potential effect of county-level income inequality on health varies across SES groups. We used the Health and Retirement Study, a nationally representative study of Americans over the age of 50. Using propensity score matching, we selected SES-comparable individuals living in high-income inequality counties and in low-income inequality counties. We examined differences in self-rated overall health outcomes and in other specific physical/mental health outcomes between the two groups using logistic regression (n = 34,994) and imposing different sample restrictions based on residential duration in the area. We then used logistic regression with interactions to assess whether, and if so how, health outcomes differed among participants of different SES groups defined by wealth, income, and education. In bivariate analyses of the unmatched full sample, adults living in high-income inequality counties have worse health outcomes for most health measures. After propensity score matching, adults in high-income inequality counties had worse self-rated health status (AOR = 1.12; 95% CI 1.04-1.19) and were more likely to report diagnosed psychiatric problems (AOR = 1.08; 95% CI 0.99-1.19) than their matched counterparts in low-income inequality counties. These associations were stronger with longer-term residents in the area. Adverse health outcomes associated with living in high-income inequality counties were significant particularly for individuals in the 30(th) or greater percentiles of income/wealth distribution and those without a college education. In summary, after using more precise matching methods to compare individuals with similar characteristics and addressing measurement error by excluding more recently arrived county residents, adults living in high-income inequality counties had worse reported overall physical and mental health than adults living in low-income inequality counties.


Amino acid adequacy in pathophysiological states.
Amino acid utilization and, therefore, demand differ between the healthy state and various disease states. In the healthy state most circulating amino acids are derived from dietary proteins that are stored and broken down in the gut and released gradually into the portal circulation, and from continuous turnover of body protein. In disease states, the amino acid composition of amino acids derived from periferal protein breakdown and released in the circulation, is different, for example because a substantial part of the branched-chain amino acids is broken down to yield glutamine and alanine, which are released in the circulation. It appears to be advantageous to mimic this continuous autoinfusion in patients, dependent of parenteral of enteral tube feeding. In disease, different endpoints should be used to assess the adequacy of the administered amino acid mix. Maintenance of a positive nitrogen balance and growth is less important than support of wound healing and immune function. Several amino acids such as glutamine, cysteine, and taurine are shown or suggested to be conditionally essential in disease, and to form substrate in the stressed patient for anabolic processes in liver, immune system, and injured sites. Amino acid toxicity is rare, and protein restriction for patients with renal or liver failure is obsolete because this only aggravated malnutrition. A true example of protein toxicity consists of gastrointestinal hemorrhage that precipitates hepatic encephalopathy in liver insufficiency, most likely because hemoglobin is an unbalanced protein because it lacks the essential amino acid isoleucine.


Radiocesium discharge from paddy fields with different initial scrapings for decontamination after the Fukushima Dai-ichi Nuclear Power Plant accident.
To explore the behavior of radionuclides released after the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident in March 2011, and the distribution of radiocesium in paddy fields, we monitored radiocesium (Cs) and suspended sediment (SS) discharge from paddy fields. We proposed a rating scale for measuring the effectiveness of surface soil removal. Our experimental plots in paddy fields were located ∼40 km from the FDNPP. Two plots were established: one in a paddy field where surface soil was not removed (the "normally cultivated paddy field") and the second in a paddy field where the top 5-10 cm of soil was removed before cultivation (the "surface-removed paddy field"). The amounts of Cs and SS discharge from the paddy fields were continuously measured from June to August 2011. The Cs soil inventory measured 3 months after the FDNPP accident was approximately 200 kBq m(-2). However, after removing the surface soil, the concentration of Cs-137 decreased to 5 kBq m(-2). SS discharged from the normally cultivated and surface-removed paddy fields after puddling (mixing of soil and water before planting rice) was 11.0 kg and 3.1 kg, respectively, and Cs-137 discharge was 630,000 Bq (1240 Bq m(-2)) and 24,800 Bq (47.8 Bq m(-2)), respectively. The total amount of SS discharge after irrigation (natural rainfall-runoff) was 5.5 kg for the normally cultivated field and 70 kg for the surface-removed field, and the total amounts of Cs-137 discharge were 51,900 Bq (102 Bq m(-2)) and 165,000 Bq (317 Bq m(-2)), respectively. During the irrigation period, discharge from the surface-removed plot showed a twofold greater inflow than that from the normally cultivated plot. Thus, Cs inflow may originate from the upper canal. The topsoil removal process eliminated at least approximately 95% of the Cs-137, but upstream water contaminated with Cs-137 flowed into the paddy field. Therefore, to accurately determine the Cs discharge, it is important to examine Cs inflow from the upper channel. Furthermore, puddling and irrigation processes inhibit the discharge of radiocesium downstream. This indicates that water control in paddy fields is an important process in the prevention of river pollution and radionuclide transfer.


Deletion of CASK in mice is lethal and impairs synaptic function.
CASK is an evolutionarily conserved multidomain protein composed of an N-terminal Ca2+/calmodulin-kinase domain, central PDZ and SH3 domains, and a C-terminal guanylate kinase domain. Many potential activities for CASK have been suggested, including functions in scaffolding the synapse, in organizing ion channels, and in regulating neuronal gene transcription. To better define the physiological importance of CASK, we have now analyzed CASK "knockdown" mice in which CASK expression was suppressed by approximately 70%, and CASK knockout (KO) mice, in which CASK expression was abolished. CASK knockdown mice are viable but smaller than WT mice, whereas CASK KO mice die at first day after birth. CASK KO mice exhibit no major developmental abnormalities apart from a partially penetrant cleft palate syndrome. In CASK-deficient neurons, the levels of the CASK-interacting proteins Mints, Veli/Mals, and neurexins are decreased, whereas the level of neuroligin 1 (which binds to neurexins that in turn bind to CASK) is increased. Neurons lacking CASK display overall normal electrical properties and form ultrastructurally normal synapses. However, glutamatergic spontaneous synaptic release events are increased, and GABAergic synaptic release events are decreased in CASK-deficient neurons. In contrast to spontaneous neurotransmitter release, evoked release exhibited no major changes. Our data suggest that CASK, the only member of the membrane-associated guanylate kinase protein family that contains a Ca2+/calmodulin-dependent kinase domain, is required for mouse survival and performs a selectively essential function without being in itself required for core activities of neurons, such as membrane excitability, Ca2+-triggered presynaptic release, or postsynaptic receptor functions.


Apoptosis induced by infection of primary brain cultures with diverse human immunodeficiency virus type 1 isolates: evidence for a role of the envelope.
Apoptosis of neurons and astrocytes is induced by human immunodeficiency type 1 (HIV-1) infection in vitro and has been demonstrated in brain tissue from patients with AIDS. We analyzed a panel of diverse HIV-1 primary isolates for the ability to replicate and induce neuronal and astrocyte apoptosis in primary human brain cultures. Apoptosis was induced three- to eightfold by infection with the blood-derived HIV-1 isolates 89.6, SG3, and ADA. In contrast, the brain-derived HIV-1 isolates YU2, JRFL, DS-br, RC-br, and KJ-br did not induce significant levels of apoptosis. The ability of HIV-1 isolates to induce apoptosis was independent of their replication capacity. Studies of recombinant chimeras between the SG3 and YU2 viruses showed that replacement of the YU2 Env with the SG3 Env was sufficient to confer the ability to induce apoptosis to the YU2 virus. Replacement of the Env V3 regions alone largely conferred the phenotypes of the parental clones. The SG3 Env used CXCR4 and CCR3 as coreceptors for virus entry, whereas YU2 used CCR5 and CCR3. The V3 regions of SG3 and YU2 conferred the ability to use CXCR4 and CCR5, respectively. In contrast, the 3' region of Env, particularly the C3V4 region, was required in conjunction with the V3 region for efficient use of CCR3. These results provide evidence that Env is a major determinant of neurodegenerative mechanisms associated with HIV-1 infection in vitro and raise the possibility that blood-derived viruses which emerge during the late stages of disease may affect disease progression in the central nervous system.


Hepatocellular carcinoma: natural history, current management, and emerging tools.
Hepatocellular carcinoma (HCC) is the most common primary liver tumor and represents the third-leading cause of cancer-related death in the world. The incidence of HCC continues to increase worldwide, with a unique geographic, age, and sex distribution. The most important risk factor associated with HCC is liver cirrhosis, with the majority of cases caused by chronic infection with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary prevention in the form of HBV vaccination has led to a significant decrease in HBV-related HCC, and initiation of antiviral therapy appears to reduce the incidence of HCC in patients with chronic HBV or HCV infection. Additionally, the use of ultrasonography enables the early detection of small liver tumors and forms the backbone of recommended surveillance programs for patients at high risk for the development of HCC. Cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, represent further noninvasive techniques that are increasingly employed to diagnose HCC in patients with cirrhosis. The mainstay of potentially curative therapy includes surgery - either resection or liver transplantation. However, most patients are ineligible for surgery, because of either advanced disease or underlying liver dysfunction, and are managed with locoregional and/or systemic therapies. Randomized controlled trials have demonstrated a survival benefit with both local therapies, either ablation or embolization, and systemic therapy in the form of the multikinase inhibitor sorafenib. Despite this, median survival remains poor and recurrence rates significant. Further advances in our understanding of the molecular pathogenesis of HCC hold promise in improving the diagnosis and treatment of this highly lethal cancer.


Psychometric assessment of the French European Developmental Coordination Disorder Questionnaire (DCDQ-FE).
The Developmental Coordination Disorder Questionnaire'07 (DCDQ'07) is a parent-report measure to identify children at risk for Developmental Coordination Disorder (DCD). We developed a French version of the DCDQ'07 (DCDQ-FE) that has shown excellent inter-language reliability (intraclass correlation coefficient (ICC) = 0.91) and is culturally relevant for use in European countries. The aims of this study were to examine the internal consistency, test-retest reliability, construct validity of the Developmental Coordination Disorder Questionnaire-French European (DCDQ-FE), as well as establish a cut-off score. The psychometric properties of the DCDQ-FE were examined with a clinical group of 30 children (mean age: 9.4 years, SD = 2.6) and a control group of 43 children (mean age: 9.1 years, SD = 2.4). Their parents (n = 73) filled out the DCDQ-FE at a first sitting and 70 of them filled it out 38 days later in average for test-retest reliability. The children were assessed using the Movement Assessment Battery for Children-2 (MABC-2) so as to measure the convergent validity of the DCDQ-FE. The cut-off score was determined with an additional sample of 42 children according to scores on the MABC-2 (≥ 16th percentile) (n = 115). Internal consistency of the DCDQ-FE was excellent (Cronbach's alpha = 0.96) and test-retest reliability was good (ICC = 0.956) with no differences between scores obtained at the two sittings (p > 0.05). Differences in scores between children in the clinical and control groups (Z = -6.58, p < 0.001) provide evidence of construct validity. The correlation obtained between DCDQ-FE and MABC-2 scores (Spearman's rho correlation coefficient = 0.802, p < 0.001) supports convergent validity. Using a cut-off of 56, overall sensitivity and specificity were 85.0% and 81.6% respectively (area under the curve = 0.896). The DCDQ-FE is a reliable and valid questionnaire for detecting children who are at risk for DCD in a European-French population of children aged 5 to 15 years old.


Reactions of persons with dementia to caregivers singing in morning care situations.
'Music therapeutic caregiving', when caregivers sing for or together with persons with severe dementia during care situations, has been suggested as a way to reduce problematic behaviors in dementia care. The present study implemented this technique as an intervention in dementia care. Six caregivers participated in group interviews about their experiences of morning care situations without and with'Music therapeutic caregiving'. Through a qualitative content analysis two themes emerged.'Being in a different reality' was based on'usual' morning care situations. The caregivers' experienced the persons with dementia as absent-minded; communication and cooperation were difficult. The second theme,'Being present', was based on morning care situations with the intervention. The caregivers described communication as enhanced; the persons with dementia expressed themselves more appropriately, making cooperation possible. The results indicate that'Music therapeutic caregiving' might lead to a more positive experience of the person with dementia and seems to increase receptivity to caregiving.


Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of negative-sense RNA viruses.
Although arthropods are important viral vectors, the biodiversity of arthropod viruses, as well as the role that arthropods have played in viral origins and evolution, is unclear. Through RNA sequencing of 70 arthropod species we discovered 112 novel viruses that appear to be ancestral to much of the documented genetic diversity of negative-sense RNA viruses, a number of which are also present as endogenous genomic copies. With this greatly enriched diversity we revealed that arthropods contain viruses that fall basal to major virus groups, including the vertebrate-specific arenaviruses, filoviruses, hantaviruses, influenza viruses, lyssaviruses, and paramyxoviruses. We similarly documented a remarkable diversity of genome structures in arthropod viruses, including a putative circular form, that sheds new light on the evolution of genome organization. Hence, arthropods are a major reservoir of viral genetic diversity and have likely been central to viral evolution.


A new virtual ring-based system matrix generator for iterative image reconstruction in high resolution small volume PET systems.
A common approach to improving the spatial resolution of small animal PET scanners is to reduce the size of scintillation crystals and/or employ high resolution pixellated semiconductor detectors. The large number of detector elements results in the system matrix--an essential part of statistical iterative reconstruction algorithms--becoming impractically large. In this paper, we propose a methodology for system matrix modelling which utilises a virtual single-layer detector ring to greatly reduce the size of the system matrix without sacrificing precision. Two methods for populating the system matrix are compared; the first utilises a geometrically-derived system matrix based on Siddon's ray tracer method with the addition of an accurate detector response function, while the second uses Monte Carlo simulation to populate the system matrix. The effectiveness of both variations of the proposed technique is demonstrated via simulations of PETiPIX, an ultra high spatial resolution small animal PET scanner featuring high-resolution DoI capabilities, which has previously been simulated and characterised using classical image reconstruction methods. Compression factors of 5 x 10(7) and 2.5 x 10(7)are achieved using this methodology for the system matrices produced using the geometric and Monte Carlo-based approaches, respectively, requiring a total of 0.5-1.2 GB of memory-resident storage. Images reconstructed from Monte Carlo simulations of various point source and phantom models, produced using system matrices generated via both geometric and simulation methods, are used to evaluate the quality of the resulting system matrix in terms of achievable spatial resolution and the CRC, CoV and CW-SSIM index image quality metrics. The Monte Carlo-based system matrix is shown to provide the best image quality at the cost of substantial one-off computational effort and a lower (but still practical) compression factor. Finally, a straightforward extension of the virtual ring method to a three dimensional virtual cylinder is demonstrated using a 3D DoI PET scanner.


Canadian Stroke Best Practice Recommendations: Rehabilitation, Recovery, and Community Participation following Stroke. Part Two: Transitions and Community Participation Following Stroke.
The sixth update of the Canadian Stroke Best Practice Recommendations for Transitions and Community Participation following Stroke is a comprehensive set of evidence-based guidelines addressing issues faced by people following an acute stroke event. Establishing a coordinated and seamless system of care that supports progress achieved during the initial recovery stages throughout the transition to the community is more essential than ever as the medical complexity of people with stroke is also on the rise. All members of the health-care team engaged with people with stroke, their families, and caregivers are responsible for partnerships and collaborations to ensure successful transitions and return to the community following stroke. These guidelines reinforce the growing and changing body of research evidence available to guide ongoing screening, assessment, and management of individuals following stroke as they move from one phase and stage of care to the next without "falling through the cracks." It also recognizes the growing role of family and informal caregivers in providing significant hours of support that disrupt their own lives and responsibilities and addresses their support and educational needs. According to Statistics Canada, in 2012, eight million Canadians provided care to family members or friends with a long-term health condition, disability, or problems associated with aging. These recommendations incorporate aspects that were previously in the rehabilitation module for the purposes of streamlining, and both modules should be reviewed in order to provide comprehensive care addressing recovery and community reintegration and participation. These recommendations cover topics related to support and education of people with stroke, families, and caregivers during transitions and community reintegration. They include interprofessional planning and communication, return to driving, vocational roles, leisure activities and relationships and sexuality, and transition to long-term care.


Mechanism of bilirubin diglucuronide formation in intact rats: bilirubin diglucuronide formation in vivo.
Although it is well established that bilirubin monoglucuronide is formed in the liver from bilirubin by a microsomal bilirubin uridine diphosphate (UDP)-glucuronosyltransferase, the subcellular site of conversion of monoglucuronide to diglucuronide and the molecular mechanism involved in diglucuronide synthesis have not been identified. Based on in vitro studies, it has been proposed that two fundamentally different enzyme systems may be involved in diglucuronide synthesis in rat liver: (a) a microsomal UDP-glucuronosyltransferase system requiring UDP-glucuronic acid as sugar donor or (b) a transglucuronidation mechanism that involves transfer of a glucuronosyl residue from one monoglucuronide molecule to another, catalyzed by a liver plasma membrane enzyme. To clarify the mechanism by which bilirubin monoglucuronide is converted in vivo to diglucuronide, three different experimental approaches were used. First, normal rats were injected with either equal amounts of bilirubin-IIIalpha [(14)C]monoglucuronide and unlabeled bilirubin-XIIIalpha monoglucuronide, or bilirubin-XIIIalpha [(14)C]monoglucuronide and unlabeled bilirubin-IIIalpha monoglucuronide. Analysis of radiolabeled diglucuronide excreted in bile showed that [(14)C]glucuronosyl residues were not transferred between monoglucuronide molecules. Second, in normal rats infused intravenously with dual-labeled [(3)H]bilirubin [(14)C]monoglucuronide, no transfer or exchange of the [(14)C]glucuronosyl group between injected and endogenously produced bilirubin monoglucuronide could be detected in the excreted bilirubin diglucuronide. Third, in homozygous Gunn rats, injected (14)C-labeled or unlabeled bilirubin mono- or diglucuronides were excreted in bile unchanged (except that diglucuronide was hydrolyzed to a minor degree). This indicates that Gunn rats, which lack bilirubin UDP-glucuronosyltransferase activity, are unable to convert injected monoglucuronide to diglucuronide. Collectively, these findings establish that a transglucuronidation mechanism is not operational in vivo and support the concept that bilirubin diglucuronide is formed by a microsomal UDP-glucuronosyltransferase system.


The molecular basis of erythrocyte shape.
Recent discoveries about the molecular organization and physical properties of the mammalian erythrocyte membrane and its associated structural proteins can now be used to explain, and may eventually be used to predict, the shape of the erythrocyte. Such explanations are possible because the relatively few structural proteins of the erythrocyte are regularly distributed over the entire cytoplasmic surface of the cell membrane and because the well-understood topological associations of these proteins seem to be stable in comparison with the time required for the cell to change shape. These simplifications make the erythrocyte the first nonmuscle cell for which it will be possible to extend our knowledge of molecular interactions to the next hierarchical level of organization that deals with shape and shape transformations.


Irritative and sensory disturbances in oral implantology. Literature review.
The aim of this study was to review irritative and sensory disturbances following placement of dental implants. A literature search was made of PubMed for articles published between 2000 and 2010. Studies that reported sensory disturbances directly caused by the placement of dental implants were included. Sensory deficits or trigeminal neuropathy are caused by damage to the third branch of the trigeminal nerve during surgery. This manifests in the immediate postoperative period as a sensory deficit not usually associated with pain and generally transient. The literature reviewed reported irritative and sensory disturbances caused during surgery, after surgery, and as a result of complications. Postoperative pain appears after oral surgery as a result of inflammation associated with damage to tissue during surgery. Pain due to postoperative complications following implant placement was classified as neurogenic pain, peri-implant pain and bone pain.


Warmer springs disrupt the synchrony of oak and winter moth phenology.
Spring temperatures have increased over the past 25 years, to which a wide variety of organisms have responded. The outstanding question is whether these responses match the temperature-induced shift of the selection pressures acting on these organisms. Organisms have evolved response mechanisms that are only adaptive given the existing relationship between the cues organisms use and the selection pressures acting on them. Global warming may disrupt ecosystem interactions because it alters these relationships and micro-evolution may be slow in tracking these changes. In particular, such shifts have serious consequences for ecosystem functioning for the tight multitrophic interactions involved in the timing of reproduction and growth. We determined the response of winter moth (Operophtera brumata) egg hatching and oak (Quercus robur) bud burst to temperature, a system with strong selection on synchronization. We show that there has been poor synchrony in recent warm springs, which is due to an increase in spring temperatures without a decrease in the incidence of freezing spells in winter. This is a clear warning that such changes in temperature patterns may affect ecosystem interactions more strongly than changes in mean temperature.


Avoiding local optima of the joint entropy prior in limited view tomography using a multiresolution scheme.
The incorporation of anatomical reference images into limited view transmission tomography has been attempted previously by using the joint entropy prior. However, this prior has been found to be sensitive to local optima. Here, we propose to increase robustness to local optima by using a multiresolution optimisation scheme. To our knowledge, this is the first work to apply multiresolution optimisation to the joint entropy prior in limited view transmission tomography. The results show a substantial mitigation of the sensitivity to local optima, as well as a robustness to missing as well as extra regions in the anatomical reference image. In addition, we demonstrate the method's robustness to misalignment between the reconstruction and the anatomical reference image.


Effects of neurotoxin - anatoxin-a on common carp (Cyprinus carpio L.) innate immune cells in vitro.
The aim of this study was to determine if cyanoneurotoxin - anatoxin-a (ANTX-a) alters the essential functions of innate immune cells such as free radicals generation in phagocytic cells and phagocytosis. In the experiments pure ANTX-a was used at concentrations of 0.01, 0.05, 0.1 and 1 µg/ml RPMI-1640 medium. Phagocytes were isolated from carp blood and pronephros. Relative changes in intracellular total free radical presence in fish phagocytes were monitored using a fluorescent probe, dichlorodihydrofluorescin DiOxyQ (DCFH-DiOxyQ) which detects hydrogen peroxide (H2O2), nitric oxide (NO), peroxyl radical and peroxynitrite anion. Phagocytic activity of fish leukocytes was analyzed with a Vybrant phagocytosis assay kit. The H2O2 level generated in response to ANTX-a at the highest used concentration was significantly suppressed in pronephros but not in blood phagocytes. Moreover, it was observed that generation of superoxide radicals and nitrite formation was significantly increased in blood and pronephros phagocytes after incubation with lower concentrations of the neurotoxin. The phagocytosis of fish leukocytes was significantly reduced at the two highest used toxin concentrations (0.1 and 1 µg/ml medium). This findings suggests that ANTX-a could change innate immunity and reduced adaptive immunity after stress induced by cyanobacterial blooms.


Further metabolism of FK506 (tacrolimus). Identification and biological activities of the metabolites oxidized at multiple sites of FK506.
To characterize the metabolic pathway of FK506 (tacrolimus), FK506 or its 31-O-desmethyl metabolite was incubated with liver microsomes prepared from dexamethasone-treated rats in the presence of a NADPH-generating system under aerobic conditions. Besides the four oxidized metabolites already reported, four new metabolites were isolated and identified by HPLC, mass spectrometry, and NMR spectroscopy, and their biological activities were examined. The di-demethylated metabolites at the 15- and 31-, 13- and 31-, and 13- and 15-methoxy groups of FK506, were designated respectively as M-V, M-VI, and M-VII. The fourth, M-VIII, was the metabolite produced after O-demethylation at the 31-methoxy group and formation of a fused 10-membered ring structure through the 19- to 22-carbon of the macrolide ring after oxidation of the 19-methyl group, and of the 36- and 37-vinyl group of FK506. The immunosuppressive activity of the isolated metabolites was estimated in a mouse mixed lymphocyte reaction system and the IC50 values for M-V, M-VI, M-VII, M-VIII, and FK506 were > 1000, 8.78, > 1000, 15.27, and 0.11 ng/ml, respectively. Reactivity of the metabolites with mouse anti-FK506 monoclonal antibody was studied and immunocrossreactivity of M-V was 92.3% of FK506, but no reactivity was observed for M-VI, M-VII, and M-VIII. FK506 thus was metabolized at multiple sites by rat hepatic microsomes and the metabolites formed (M-V) - (M-VIII) exhibited weak or negligible immunosuppressive activity.


Mutations in Kruppel-like factor 1 cause transfusion-dependent hemolytic anemia and persistence of embryonic globin gene expression.
In this study, we report on 8 compound heterozygotes for mutations in the key erythroid transcription factor Krüppel-like factor 1 in patients who presented with severe, transfusion-dependent hemolytic anemia. In most cases, the red cells were hypochromic and microcytic, consistent with abnormalities in hemoglobin synthesis. In addition, in many cases, the red cells resembled those seen in patients with membrane defects or enzymopathies, known as chronic nonspherocytic hemolytic anemia (CNSHA). Analysis of RNA and protein in primary erythroid cells from these individuals provided evidence of abnormal globin synthesis, with persistent expression of fetal hemoglobin and, most remarkably, expression of large quantities of embryonic globins in postnatal life. The red cell membranes were abnormal, most notably expressing reduced amounts of CD44 and, consequently, manifesting the rare In(Lu) blood group. Finally, all tested patients showed abnormally low levels of the red cell enzyme pyruvate kinase, a known cause of CNSHA. These patients define a new type of severe, transfusion-dependent CNSHA caused by mutations in a trans-acting factor (Krüppel-like factor 1) and reveal an important pathway regulating embryonic globin gene expression in adult humans.


Treating incarcerated women: gender matters.
Research on incarcerated women has shown they have a high degree of comorbid psychopathology, including substance dependence, posttraumatic stress disorder (PTSD), antisocial personality disorder (ASPD), and major depression. Incarcerated women differ from their community peers by having more symptoms related to addiction, ASPD, and PTSD. At the same time, incarcerated women are every bit as likely as incarcerated men to be dependent on drugs and almost as likely to be dependent on alcohol. What emerges is a picture of the incarcerated woman far more likely to have had traumatic experiences, including early sexual and physical abuse, than her male peers but every bit as likely to have substance dependence and, in some correctional populations (eg, sentenced felons), antisocial personality disorder. Central to the discussion of how best to treat female offenders is the need to address how programs would best be structured for women with severe substance dependence, substantial trauma histories, and personality pathology, including ASPD. Incarcerated women are a population with complex medical and mental health needs and are likely to be high users of services within the correctional system. This poses challenges to a system already stretched thin in caring for these complex inmates. This article emphasizes that gender differences need to be appreciated, and that service delivery to male and female inmates needs to be structured with gender in mind. The article recommends case management, treatment in highly structured therapeutic communities, and emphasizing abstinence from substances and development of skill sets to engage in healthy relationships.A major future challenge lies in researching treatment interventions for women in the correctional system. There are few existing trials of treatment efficacy and, as previously noted, the incarcerated female population differs from populations of incarcerated men and women in the community. Opiate-dependent women undergoing treatment in the community may prove to be a reasonable comparison group in beginning to develop evidence-based treatment for female offenders in prisons and jails. Ultimately, the development of services for incarcerated women will consider gender, race, and psychopathology in determining treatment setting and modalities. We are on new ground. It is a promising and exciting time to be involved with treatment of female offenders.


Closed fringe demodulation using phase decomposition by Fourier basis functions.
We report a new technique for the demodulation of a closed fringe pattern by representing the phase as a weighted linear combination of a certain number of linearly independent Fourier basis functions in a given row/column at a time. A state space model is developed with the weights of the basis functions as the elements of the state vector. The iterative extended Kalman filter is effectively utilized for the robust estimation of the weights. A coarse estimate of the fringe density based on the fringe frequency map is used to determine the initial row/column to start with and subsequently the optimal number of basis functions. The performance of the proposed method is evaluated with several noisy fringe patterns. Experimental results are also reported to support the practical applicability of the proposed method.


Maxillomandibular relationships in patients with dentofacial deformities: diagnostic criteria utilizing three cephalometric analyses.
This paper evaluates the quantitative and qualitative diagnostic criteria utilizing three cephalometric assessments of the maxillomandibular relationship. Evaluation was applied to pretreatment and posttreatment cephalometric radiographs of 13 patients with dentofacial deformities that were corrected by combined orthodontic-surgical treatment with good esthetic and functional results. These evaluations were analyzed individually and compared to one another and with the type of surgery performed. Results indicate that (1) dentoskeletal discrepancy cases need evaluations in addition to conventional celphalometric analysis; (2) the evaluation based on SNA, SNB, and ANB angles is not reliable when there is an alteration in the lower one-third facial height; (3) the Wits appraisal shows good reading capacity but must be supplemented by additional analyses, because it does not differentiate the precise location origin of the deformities; (4) the McNamara analysis shows higher correlation between the actual surgical corrections performed, when the nasolabial angle is considered a primary guide to evaluate the position of the maxilla; and (5) notwithstanding the diagnostic capacity of the McNamara analysis, it has a definite tendency to present discrepancy values larger than would be inferred from the correction adopted by the surgeon, with the exception of mandibular advancement in cases of Class II with mandibular retrusion.


Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues.
We have identified tens of thousands of short extrachromosomal circular DNAs (microDNA) in mouse tissues as well as mouse and human cell lines. These microDNAs are 200 to 400 base pairs long, are derived from unique nonrepetitive sequence, and are enriched in the 5'-untranslated regions of genes, exons, and CpG islands. Chromosomal loci that are enriched sources of microDNA in the adult brain are somatically mosaic for microdeletions that appear to arise from the excision of microDNAs. Germline microdeletions identified by the "Thousand Genomes" project may also arise from the excision of microDNAs in the germline lineage. We have thus identified a previously unknown DNA entity in mammalian cells and provide evidence that their generation leaves behind deletions in different genomic loci.


The Controlling Nutritional Status Score and Postoperative Complication Risk in Gastrointestinal and Hepatopancreatobiliary Surgical Oncology: A Systematic Review and Meta-Analysis.
The controlling nutritional status (CONUT) score is associated with prognosis in gastrointestinal (GI) cancer patients, but the clinical significance of the CONUT score for postoperative short-term outcome remains controversial. The aim of this study was to investigate the impact of the CONUT score on postoperative outcomes in patients with GI and hepatopancreatobiliary (HPB) cancers. We conducted a systematic literature search of Embase, Medline Ovid, Web of Science, Cochrane CENTRAL, and Google Scholar. Meta-analyses were performed to estimate the pooled risk ratio (RR) for postoperative complications in patients with lower -CONUT score versus higher CONUT score. Furthermore, we explored the most appropriate cutoff value of the CONUT score to predict postoperative complications. Ten retrospective studies (5,138 patients) were included in this meta-analysis. Patients with higher CONUT score had an increased risk of mortality (RR 5.38, 95% CI 2.19-13.2, p < 0.001, I2 = 0%), postoperative major complications (RR 1.56, 95% CI 1.05-2.33, p= 0.03, I2 = 79%), and overall complications (RR 1.38, 95% CI 1.16-1.63, p < 0.001, I2 = 6%). We found that the cutoff of CONUT ≤4 vs. CONUT ≥5 had the highest pooled RR compared with other cutoff values (RR 4.79, 95% CI 0.97-23.5, p= 0.05, I2 = 91%). In conclusion, the present study suggests that the preoperative CONUT score was associated with an increased risk of mortality and complications in GI and HPB surgical oncology. Patients with higher CONUT score as compared with those having a lower score had approximately a fivefold mortality risk and an increased risk up to 55% on major and overall complications after GI and HPB surgery. Our analysis indicates that the appropriate cutoff value of the CONUT score to predict postoperative major complications would be between 4 and 5. The preoperative evaluation of the CONUT score would be helpful for predicting the risk of postoperative outcomes.


Two-color immunofluorescence and flow cytometric analysis of lamina propria lymphocyte subsets in ulcerative colitis and Crohn's disease.
By using two-color immunofluorescence with fluorescein isothiocyanate (FITC) and phycoerythrin (PE)-labelled monoclonal antibodies and multiparameter flow cytometry, we investigated lamina propria lymphocyte subsets of patients with ulcerative colitis (UC) and Crohn's disease (CD). Leu-3/Leu-2 (CD4/CD8) ratio of lamina propria lymphocytes (LPL) of CD (mean +/- SD: 1.9 +/- 0.8, P less than 0.01) was significantly decreased compared with controls (3.3 +/- 1.1), because of an increased number of CD8+ lymphocytes. The majority of lamina propria CD4+ cells were CD4+, Leu-8- and CD4+, CD45R- both in controls and IBD tissue. Many lamina propria T lymphocytes were activated, expressing HLA-DR antigen not only in IBD but also in controls. NK cells defined by CD16 and CD 56 (3.0 +/- 1.4%, P less than 0.01) were significantly decreased in patients with UC compared with controls (6.5 +/- 3.0%). A low proportion of B cells in the intestinal mucosa expressed Leu-8 antigen and CD23 antigen. The proportion of activated B cells of LPL was high in IBD mucosa as well as normal mucosa. These findings suggest that local activation of B cells leads to the loss of the expression of Leu-8 antigen and CD23.


Cerebellar involvement in progressive supranuclear palsy: A clinicopathological study.
The clinical heterogeneity of progressive supranuclear palsy (PSP), which is classified as classic Richardson's syndrome (RS) and PSP-Parkinsonism (PSP-P), has been previously discussed. We retrospectively analyzed 22 consecutive Japanese patients with pathologically proven PSP to investigate the clinicopathological heterogeneity. We investigated the clinical features both early in and at any time during the disease course. The pathological severities of neuronal loss with gliosis and tau pathology were also evaluated. On the basis of the clinical features, 10 patients were categorized as having RS, and 8 were categorized as having PSP-P. Four patients presenting with cerebellar ataxia or cerebral cortical signs were categorized as having unclassifiable PSP. Among them, 3 developed cerebellar ataxia as the initial and principal symptom. Notably, tau-positive inclusion bodies in Purkinje cells were significantly more frequently observed in the patients with cerebellar ataxia than in those without cerebellar ataxia. All the patients with cerebellar ataxia exhibited more neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus than those without cerebellar ataxia. This study confirms the wide spectrum of clinicopathological manifestations associated with PSP regardless of different ethnic origin, and demonstrates that PSP patients manifest cerebellar ataxia.


Different dimensions of HIV-related stigma may have opposite effects on hiv testing: evidence among young men and women in South Africa.
Although HIV-related stigma in general is known to deter HIV-testing, the extent to which different dimensions of stigma independently influence testing behaviour is poorly understood. We used data on young black men (n = 553) and women (n = 674) from the 2009 Cape Area Panel Study to examine the independent effects of stigmatising attitudes, perceived stigma and observed enacted stigma on HIV-testing. Multivariate logistic regression models showed that stigma had a strong relationship with HIV-testing among women, but not men. Women who held stigmatising attitudes were more likely to have been tested (OR 3, p < 0.01), while perceived stigma (OR 0.61, p < 0.1) and observed enacted stigma (OR 0.42, p < 0.01) reduced the odds significantly of women having had an HIV test. Our findings highlight that different dimensions of stigma may have opposite effects on HIV testing, and point towards the need for interventions that limit the impact of enacted and perceived stigma on HIV-testing among women.


Management of heart failure in primary care after implementation of the National Service Framework for Coronary Heart Disease: a cross-sectional study.
To compare the management of heart failure with the standards set out in the National Service Framework for Coronary Heart Disease. A cross-sectional study in 26 general practices, with a combined list size of 256,188, that are members of the Kent, Surrey and Sussex Primary Care Research Network. Information was extracted on the management of 2129 patients with heart failure, of whom 2097 were aged 45 years and over. The prevalence of heart failure was 8.3 per 1000. Prevalence rates increased with age, from 0.2 per 1000 in people aged under 35 years of age to 125 per 1000 in those aged 85 years and over. Coronary heart disease (present in 47%) was the most common comorbid condition in men with heart failure, whereas hypertension (present in 46%) was the most common condition in women. Recording of cardiovascular risk factors was generally higher in younger patients than in older patients, and in men than in women. Blood pressure (92% of men and 90% of women) and smoking status (84% of men and 77% of women) were generally the best-recorded cardiovascular risk factors. Blood electrolytes were recorded in about 83% of men and 75% of women. Only 17% of men and 11% of women with heart failure had a record of undergoing an echocardiogram. Use of angiotensin-converting enzyme (ACE) inhibitors or antagonists was 76% in men with heart failure and 68% in women; lowest rates were seen in older patients. Uptake of influenza immunization was generally high, at 85% in men and 84% in women. The use of ACE inhibitors in patients with heart failure was higher than in some previous studies. However, many patients have no documentation in their computerized medical records of having undergone key investigations, such as echocardiography.


Evaluation of the Hepatitis B Vaccination Programme in Medical Students in a Dutch University Hospital.
Healthcare workers (HCW) are at increased risk of contracting hepatitis B virus (HBV) and are, therefore, vaccinated pre-exposure. In this study, the HBV vaccination programme for medical students in a university hospital in the Netherlands was evaluated. In the first part, the effectiveness of the programme, which consisted of a vaccination with Engerix-B® at 0, 1, and 6 months, was retrospectively evaluated over 7 years (2012-2019). In the second part of this study, we followed students (the 2019 cohort) who had previously been vaccinated against HBV vaccination (4-262 months prior to primary presentation) in order to investigate the most efficient strategy to obtain an adequate anti hepatitis B surface antigen titre. In the latter, titre determination was performed directly during primary presentation instead of giving previously vaccinated students a booster vaccination first. The vaccination programme, as evaluated in the retrospective first part of the study, was effective (surpassed the protection limit of 10 IU/L) in 98.8 percent of the students (95% CI (98.4-99.2)). In the second part of our study, we found that 80 percent (95% CI (70-87)) of the students who had previously been vaccinated against HBV were still sufficiently protected and did not require a booster vaccination. With this strategy, the previously vaccinated students needed an average of 1.4 appointments instead of the 2 appointments needed with the former strategy. This knowledge is important and can save time and resources in the process of occupational HBV vaccination of HCW.


Oral and bronchial provocation tests with aspirin for diagnosis of aspirin-induced asthma.
In 35 asthmatic patients with acetylsalicylic acid (aspirin; ASA) intolerance (AIA) and 15 asthmatics tolerating ASA well, the authors compared the diagnostic value of the placebo-controlled oral ASA versus inhaled L-lysine (L) ASA challenges. All AIA subjects gave a history of asthmatic attacks following ingestion of ASA and in all of them the intolerance was confirmed by oral challenge test over the past 10 yrs. Doses of ASA increasing in geometric progression were used in oral tests 10-312 mg (cumulative dose 500 mg); in bronchial tests 0.18-115 mg (cumulative dose 182 mg). Either challenge was considered as positive, if forced expiratory volume in one second (FEV1) dropped at least 20% from the baseline value and/or strong extrabronchial symptoms of intolerance occurred. Urinary leukotriene E4 excretion was determined at baseline and following the challenges. In 24 out of 35 patients the oral test was positive, based on a 20% decrease in FEV1. When including extrabronchial symptoms this was positive in 31 cases. Bronchial L-ASA challenge led to > or =20% fall FEV1 in 21 out of 35 cases, and in 27 cases when including extrabronchial symptoms. No correlation was observed between ASA provocative dose causing a 20% fall in FEV1, determined by the oral route compared to the inhalation route. Urinary LTE4 increased after both challenges the rise being higher following oral as compared to inhalation provocation (p=0.0001). It is concluded that both tests had similar specificity whilst the oral test showed a tendency to higher sensitivity for the clinical diagnosis of acetylsalicylic acid intolerance. The inclusion of extrabronchial symptoms into the criteria of test positivity enhanced the diagnostic value of both procedures. In both tests the highest leukotriene E4 increases were found in the presence of extrabronchial symptoms, suggesting the participation of tissues other than the lung in aspirin induced leukotriene E4 release to urine.


Tree rings, carbon dioxide, and climatic change.
Tree rings have been used in various applications to reconstruct past climates as well as to assess the effects of recent climatic and environmental change on tree growth. In this paper we briefly review two ways that tree rings provide information about climate change and CO2: (i) in determining whether recent warming during the period of instrumental observations is unusual relative to prior centuries to millennia, and thus might be related to increasing greenhouse gases; and (ii) in evaluating whether enhanced radial growth has taken place in recent decades that appears to be unexplained by climate and might instead be due to increasing atmospheric CO2 or other nutrient fertilization. It is found that a number of tree-ring studies from temperature-sensitive settings indicate unusual recent warming, although there are also exceptions at certain sites. The present tree-ring evidence for a possible CO2 fertilization effect under natural environmental conditions appears to be very limited.


Is body composition associated with an increased risk of developing anterior knee pain in adolescent female athletes?
To determine the relationship between relative body composition and body mass to height, anterior knee pain, or patellofemoral pain (PFP) in adolescent female athletes. Patellofemoral pain is common in female athletes and has an undefined etiology. The purpose of this study was to examine whether there was an association among higher body mass index (BMI), BMI z-scores, and relative body fat percentage in the development of PFP in an adolescent female athlete population. We hypothesized that female athletes who developed PFP over the course of a competitive basketball season had higher relative body mass or body fat percentage compared with those who did not develop PFP. Fifteen middle school basketball teams that consisted of 248 basketball players (mean age, 12.76 ± 1.13 years; height, 158.43 ± 7.78 cm; body mass, 52.35 ± 12.31 kg; BMI, 20.73 ± 3.88 kg/m(2)) agreed to participate in this study over the course of 2 basketball seasons, resulting in 262 athlete-seasons. Testing included the completion of the Anterior Knee Pain Scale (AKPS), International Knee Documentation Committee (IKDC) form, standardized history, physician-administered physical examination, maturational estimates, and anthropometrics. Of the 262 athlete-seasons monitored, 39 athletes developed PFP over the course of the study. The incidence rate of new PFP was 1.57 per 1000 athlete-exposures. The cumulative incidence of PFP was 14.9%. There was no difference in BMI between those who developed PFP (mean body mass, 20.2 kg/m(2); 95% CI,18.9-21.4) and those who did not develop PFP (mean body mass, 20.8 kg/m(2); 95% CI, 20.3-21.3;P > 0.05). Body mass index z-scores were not different between those who developed PFP (mean, 0.3; 95% CI, 0.7-0.6) and those who did not develop PFP (mean, 0.4; 95% CI, 0.3-0.6;P > 0.05). A similar trend was noted in relative body fat percentage, with mean scores of similar ranges in those who developed PFP (mean body fat percentage, 22.2%; 95% CI, 19.4-24.9) to the referent group who did not (mean body fat percentage, 22.9%; 95% CI, 21.8-24.1;P > 0.05). Our results do not indicate a relationship between relative body composition or relative body mass to height to the propensity to develop PFP in middle school-aged female basketball players. Although previous data indicate a relationship between higher relative body mass and overall knee injury, these data did not support this association with PFP specifically. These data suggest the underlying etiology of PFP may be neuromuscular in nature. Further research is needed to understand the predictors, etiology, and ultimate prevention of this condition.


Patterns of anti-hypertensive therapy in diabetic patients with and without reduced renal function.
Renal function deterioration is a common complication in patients with diabetes mellitus and hypertension. Appropriate use of anti-hypertensive agents and tight control of blood pressure (BP) can minimize and delay such complications. This study was performed in order to investigate the utilization patterns of anti-hypertensive agents and to evaluate BP control among diabetic-hypertensive patients with and without reduced renal function. In a retrospective cohort study, all diabetic-hypertensive patients attending The Al-Watani Medical Governmental Center from August 01, 2006 until August 01, 2007 were enrolled in the study. Patients with congestive heart failure and/or end-stage renal disease were excluded from the study. The proportion of use of five different anti-hypertensive drug classes were compared for all patients receiving 1, 2, 3, or 4 drugs, and separately among patients with and without reduced renal function. Over 60% of patients were receiving angiotensin-converting enzyme inhibitors (ACEI)/angiotensin receptor blocker (ARB), followed by diuretics (40.8%), calcium channel blockers (25.1%) and (beta-blockers (12.5%). The majority of patients (> 55%) were either on mono or no drug therapy. Patients on monotherapy were mostly receiving ACEI/ARB (60%). In patients with reduced renal function, use of diuretics, but not ACEI/ARB or CCB, was higher and 41.8% of the patients were on monotherapy compared to 46.6% in patients with normal renal function. The proportion of patients achieving good BP control was 20% with mono-therapy and 28% with combination therapy. Our study suggests that the pattern of anti-hypertensive therapy was generally consistent with inter-national guidelines. Areas of improvement include increasing use of ACEI/ARB and diuretics, decreasing the number of untreated patients, and increasing the proportion of patients with well controlled BP in this population.


High contribution of Rhizaria (Radiolaria) to vertical export in the California Current Ecosystem revealed by DNA metabarcoding.
Passive sinking of particulate organic matter (POM) is the main mechanism through which the biological pump transports surface primary production to the ocean interior. However, the contribution and variability of different biological sources to vertical export is not fully understood. Here, we use DNA metabarcoding of the 18S rRNA gene and particle interceptor traps (PITs) to characterize the taxonomic composition of particles sinking out of the photic layer in the California Current Ecosystem (CCE), a productive system with high export potential. The PITs included formalin-fixed and 'live' traps to investigate eukaryotic communities involved in the export and remineralization of sinking particles. Sequences affiliated with Radiolaria dominated the eukaryotic assemblage in fixed traps (90%), with Dinophyta and Metazoa making minor contributions. The prominence of Radiolaria decreased drastically in live traps, possibly due to selective consumption by copepods, heterotrophic nanoflagellates, and phaeodarians that were heavily enriched in these traps. These patterns were consistent across the water masses surveyed extending from the coast to offshore, despite major differences in productivity and trophic structure of the epipelagic plankton community. Our findings identify Radiolaria as major actors in export fluxes in the CCE.


Comparison the Effects of Oral Tizanidine and Tramadol on Intra- and Post-operative Shivering in Patients Underwent Spinal Anesthesia.
Heat loss and core-to-peripheral redistribution of body heat occur in patients undergoing neuraxial anesthesia resulted to decrease of core temperature and early reach of shivering threshold. Because shivering has deleterious metabolic and cardiovascular effects, it should ideally be prevented by pharmacologic or other means. Tizanidine is an alpha-2 agonist. We evaluated the usefulness of oral tizanidine (TI) and tramadol in preventing of shivering in patients undergoing spinal anesthesia for transurethral resection of the prostate (TURP). Ninety patients, scheduled for TURP with spinal anesthesia, were prospectively enrolled. Patients were randomly assigned to 1 of 3 groups. 90 min before spinal anesthesia, 30 patients received 4 mg oral TI, 30 patients received 50 mg tramadol, and 30 patients received placebo as control group. Spinal anesthesia was induced at the L3-L4 or L4-L5 interspaces with 12.5 mg bupivacaine. An investigator blinded to the drugs recorded the frequency and degree of shivering. The overall frequency and severity of shivering were significantly lower in patients treated with TI and tramadol compared to placebo (P = 0.04) (P = 0.001). There was not much difference in the nausea and vomiting of both the drugs (P = 026) (P = 011). There was no difference in hemodynamic parameters between three groups (P = 0.08) (P = 013). Oral TI and tramadol were comparable in respect to their effect in decreasing the incidence, intensity shivering when used prophylactically in patients who underwent TURP with spinal anesthesia.


Different Behavior and Response of Staphylococcus Epidermidis and Streptococcus Pneumoniae to a Ventriculoperitoneal Shunt: An in vitro Study.
Pneumococcal shunt infection is a rare event. There is no consensus on the therapeutic management of this kind of shunt infection according to literature reviews, and it seems to be different from infection with Staphylococcus epidermidis. We studied 2 shunted patients with pneumococcal meningitis, both of whom were treated with only antibiotics. The management of these cases seems to be different from that of shunt catheter infection due to these bacteria. We conducted a laboratory study to show the different behavior of pneumococcus compared to S. epidermidis regarding shunt catheter colonization. S. epidermidis and Streptococcus pneumoniae bacteria isolated from the cerebrospinal fluid of meningitis patients were incubated in sterile media. Forty-five segments of shunt catheter from silicone material were placed in 45 separate media of S. epidermidis and pneumococcus. Then each catheter was washed and cultured in blood chocolate agar growth medium in separate petri dishes via the roll plate method. The dishes were extracted from the incubator and the colony count was calculated after 72 h. The colony count was obviously different between the 2 bacteria groups, with a higher count related to S. epidermidis dishes. The colony count of the pneumococcal petri dishes was 25-35,000 (mean 14,337) and for dishes with S. epidermidis it was 14,000-100,000 (mean 50,125) (p = 0.001). The adherence of pneumococcus to shunt catheters seems to be much less than that of S. epidermidis, which produced a very low colony count when incubated with the catheter in the medium culture. S. pneumoniae meningitis in shunted patients can be managed successfully with only antibiotics. This approach can prevent problems related to the several additional surgeries required for shunt removal, a new shunt insertion, and the management of high intracranial pressure.


Cognitive performance in multiple system atrophy.
The cognitive performance of a group of patients with multiple system atrophy (MSA) of striato-nigral predominance was compared with that of age and IQ matched control subjects, using three tests sensitive to frontal lobe dysfunction and a battery sensitive to memory and learning deficits in Parkinson's disease and dementia of the Alzheimer type. The MSA group showed significant deficits in all three of the tests previously shown to be sensitive to frontal lobe dysfunction. Thus, a significant proportion of patients from the MSA group failed an attentional set-shifting test, specifically at the stage when an extra-dimensional shift was required. They were also impaired in a subject-ordered test of spatial working memory. The MSA group showed deficits mostly confined to measures of speed of thinking, rather than accuracy, on the Tower of London task. These deficits were seen in the absence of consistent impairments in language or visual perception. Moreover, the MSA group showed no significant deficits in tests of spatial and pattern recognition previously shown to be sensitive to patients early in the course of probable Alzheimer's disease and only a few patients exhibited impairment on the Warrington Recognition Memory Test. There were impairments on other tests of visual memory and learning relative to matched controls, but these could not easily be related to fundamental deficits of memory or learning. Thus, on a matching-to-sample task the patients were impaired at simultaneous but not delayed matching to sample, whereas difficulties in a pattern-location learning task were more evident at its initial, easier stages. The MSA group showed no consistent evidence of intellectual deterioration as assessed from their performance on subtests of the Wechsler Adult Intelligence Scale (WAIS) and the National Adult Reading Test (NART). Consideration of individual cases showed that there was some heterogeneity in the pattern of deficits in the MSA group, with one patient showing no impairment, even in the face of considerable physical disability. The results show a distinctive pattern of cognitive deficits, unlike those previously seen using the same tests in patients with Parkinson's and Alzheimer's diseases, and suggesting a prominent frontal-lobe-like component. The implications for concepts of 'subcortical' dementia and 'fronto-striatal' cognitive dysfunction are considered.


Light exposure patterns in healthy older and young adults.
Aging is associated with an earlier timing of circadian rhythms and a shorter phase angle between wake time and the timing of melatonin secretion or the core body temperature nadir. Light has a phase-dependent effect on the circadian pacemaker, and modifications of habitual light exposure in older people could contribute to a change in the timing of circadian rhythms or in the phase angle of entrainment. In this study, we compare natural light exposure of community-dwelling older and young subjects studied at the same time of year, focusing on the pattern of light exposure across the waking day. We recorded light exposure data for 3 to 8 days from 22 older (aged 66.01 +/- 5.83) and 22 young subjects (aged 23.41 +/- 4.57), living at home on self-selected sleepwake schedules, and matched for time of year. All subjects were from New England (latitude 42.3 degrees N to 43 degrees N). We compared the percentage of the waking day spent by older and young subjects at 4 different light levels (from very dim to very bright). We compared hourly averaged light exposure data in each group according to clock time and with respect to each subject's daily sleepwake times. Although both age groups spent more than half of their waking hours in dim or moderate room light intensity (<100 lux), we found that the older subjects spent a significantly greater percentage of their waking day in the brighter light levels (> or =1000 lux); their hourly averaged light exposure levels were also significantly greater whether we examined the data with respect to absolute clock time, to wake time, or to bed time, and this was true across all seasons. We found that healthy older people were exposed to significantly higher levels of light throughout their waking day than young people. Differences in natural light exposure may contribute to the age-related phase advance of the circadian pacemaker and its later timing relative to the sleepwake cycle. This hypothesis should be explored further in carefully designed prospective studies.


Human-robot cooperative movement training: learning a novel sensory motor transformation during walking with robotic assistance-as-needed.
A prevailing paradigm of physical rehabilitation following neurologic injury is to "assist-as-needed" in completing desired movements. Several research groups are attempting to automate this principle with robotic movement training devices and patient cooperative algorithms that encourage voluntary participation. These attempts are currently not based on computational models of motor learning. Here we assume that motor recovery from a neurologic injury can be modelled as a process of learning a novel sensory motor transformation, which allows us to study a simplified experimental protocol amenable to mathematical description. Specifically, we use a robotic force field paradigm to impose a virtual impairment on the left leg of unimpaired subjects walking on a treadmill. We then derive an "assist-as-needed" robotic training algorithm to help subjects overcome the virtual impairment and walk normally. The problem is posed as an optimization of performance error and robotic assistance. The optimal robotic movement trainer becomes an error-based controller with a forgetting factor that bounds kinematic errors while systematically reducing its assistance when those errors are small. As humans have a natural range of movement variability, we introduce an error weighting function that causes the robotic trainer to disregard this variability. We experimentally validated the controller with ten unimpaired subjects by demonstrating how it helped the subjects learn the novel sensory motor transformation necessary to counteract the virtual impairment, while also preventing them from experiencing large kinematic errors. The addition of the error weighting function allowed the robot assistance to fade to zero even though the subjects' movements were variable. We also show that in order to assist-as-needed, the robot must relax its assistance at a rate faster than that of the learning human. The assist-as-needed algorithm proposed here can limit error during the learning of a dynamic motor task. The algorithm encourages learning by decreasing its assistance as a function of the ongoing progression of movement error. This type of algorithm is well suited for helping people learn dynamic tasks for which large kinematic errors are dangerous or discouraging, and thus may prove useful for robot-assisted movement training of walking or reaching following neurologic injury.


Development and initial testing of the self-care of chronic illness inventory.
The aim was to develop and psychometrically test the self-care of chronic illness Inventory, a generic measure of self-care. Existing measures of self-care are disease-specific or behaviour-specific; no generic measure of self-care exists. Cross-sectional survey. We developed a 20-item self-report instrument based on the Middle Range Theory of Self-Care of Chronic Illness, with three separate scales measuring Self-Care Maintenance, Self-Care Monitoring, and Self-Care Management. Each of the three scales is scored separately and standardized 0-100 with higher scores indicating better self-care. After demonstrating content validity, psychometric testing was conducted in a convenience sample of 407 adults (enrolled from inpatient and outpatient settings at five sites in the United States and ResearchMatch.org). Dimensionality testing with confirmatory factor analysis preceded reliability testing. The Self-Care Maintenance scale (eight items, two dimensions: illness-related and health-promoting behaviour) fit well when tested with a two-factor confirmatory model. The Self-Care Monitoring scale (five items, single factor) fitted well. The Self-Care Management scale (seven items, two factors: autonomous and consulting behaviour), when tested with a two-factor confirmatory model, fitted adequately. A simultaneous confirmatory factor analysis on the combined set of items supported the more general model. The self-care of chronic illness inventory is adequate in reliability and validity. We suggest further testing in diverse populations of patients with chronic illnesses.


Nurse Communication About Goals of Care.
Conversations about goals of care with the patient and family are a critical component of advanced practice in oncology. However, there are often inadequate team structures, training, or resources available to assist advanced practitioners in initiating these conversations. We conducted a study to assess nurses' perceived role and communication tasks in such conversations about goals of care. In a cross-sectional survey of 109 nurses attending a comprehensive 2-day end-of-life nursing education course, nurses were asked to describe how they would participate in a "goals of care" meeting in three different scenarios. They were also asked what changes they desired in their clinical settings. Nurses overwhelmingly described that their primary task and communication role was to assess patient/family understanding. Nurses referenced their team members and team support with the least frequency across scenarios. Team roles, structure, and process were reported as areas in greatest need of change in patient/family goals of care meetings. These findings demonstrate that lack of preparation to function as a team is a barrier for nurses in communicating about goals of care, and there is a demand to move such conversations upstream in oncology care.


The novel product of a five-exon stargazin-related gene abolishes Ca(V)2.2 calcium channel expression.
We have cloned and characterized a new member of the voltage-dependent Ca(2+) channel gamma subunit family, with a novel gene structure and striking properties. Unlike the genes of other potential gamma subunits identified by their homology to the stargazin gene, CACNG7 is a five-, and not four-exon gene whose mRNA encodes a protein we have designated gamma(7). Expression of human gamma(7) has been localized specifically to brain. N-type current through Ca(V)2.2 channels was almost abolished when co-expressed transiently with gamma(7) in either Xenopus oocytes or COS-7 cells. Furthermore, immunocytochemistry and western blots show that gamma(7) has this effect by causing a large reduction in expression of Ca(V)2.2 rather than by interfering with trafficking or biophysical properties of the channel. No effect of transiently expressed gamma(7) was observed on pre-existing endogenous N-type calcium channels in sympathetic neurones. Low homology to the stargazin-like gamma subunits, different gene structure and the unique functional properties of gamma(7) imply that it represents a distinct subdivision of the family of proteins identified by their structural and sequence homology to stargazin.


Prenatal morphine exposure decreases analgesia but not K+ channel activation.
The present study has investigated the possible supraspinal adaptive changes induced by prenatal administration of morphine, including morphine-induced supraspinal antinociception in vivo, the density and binding affinity of mu-opioid receptors in the brain and the cellular action of morphine in brain slices in vitro. The cellular action of morphine was assessed by its activation of K+ channels in the ventrolateral periaqueductal gray (PAG), a crucial area for the supraspinal analgesic effect of morphine. Female rats were treated with morphine 7 days before mating at 2 mg/kg. The treatment was continued during pregnancy and after delivery at doses which increased by 1 mg/kg every 2 weeks. Experiments were conducted in the offspring at p14 days. Prenatal morphine exposure induced tolerance to supraspinal morphine-induced tail-flick response. The binding affinity and maximal binding of [(3)H]DAMGO in whole brain were not significant different between the morphine- or saline-treated dams. Autoradiographic analysis shows that the mu-opioid receptor density was decreased in the striatum, thalamus and amygdala but not in the midbrain, nucleus accumbens, hippocampus or cortex in morphine offspring. In ventrolateral PAG neurons, morphine activated inwardly rectifying K+ channels in 59% of recorded neurons of morphine offspring. Neither the magnitude of K channel activation nor the percentage of sensitive neurons was different between the saline- and morphine-treated offspring. It is concluded that prenatal morphine exposure induces tolerance to supraspinal analgesia and this tolerance is not attributed to a change in the mu-opioid receptor density or the receptor-function coupling efficiency in the midbrain periaqueductal gray.


Nutrients, foods, and dietary patterns as exposures in research: a framework for food synergy.
Evidence is synthesized that foods and food patterns act synergistically to influence the risk of several chronic diseases. Whole-grain consumption and risk of disease are presented as a model of food synergy. Food synergy is defined as additive or more than additive influences of foods and food constituents on health. Risk appears to be lower with consumption of whole grain than of refined grain; that is, benefit accrues when all edible parts of the grain are included (bran, germ, and endosperm). It appears that phytochemicals that are located in the fiber matrix, in addition to or instead of the fiber itself, are responsible for the reduced risk. Risk is further reduced if whole-grain foods are consumed in a diet otherwise high in plant foods. To gain full understanding of the pathways by which food synergies work, it is desirable to use several "top down" approaches, starting with the larger units, namely foods or food patterns, and working down to smaller units that provide protection from disease. Study of foods, food patterns, and individual nutrients or food components in reducing disease risk is seen as complementary. Epidemiologic, clinical trial, and in vitro approaches to such research are needed.


Face recognition using kernel scatter-difference-based discriminant analysis.
There are two fundamental problems with the Fisher linear discriminant analysis for face recognition. One is the singularity problem of the within-class scatter matrix due to small training sample size. The other is that it cannot efficiently describe complex nonlinear variations of face images because of its linear property. In this letter, a kernel scatter-difference-based discriminant analysis is proposed to overcome these two problems. We first use the nonlinear kernel trick to map the input data into an implicit feature space F. Then a scatter-difference-based discriminant rule is defined to analyze the data in F. The proposed method can not only produce nonlinear discriminant features but also avoid the singularity problem of the within-class scatter matrix. Extensive experiments show encouraging recognition performance of the new algorithm.