Brain anatomy and its relationship to behavior in adults with autism spectrum disorder: a multicenter magnetic resonance imaging study.
There is consensus that autism spectrum disorder (ASD) is accompanied by differences in neuroanatomy. However, the neural substrates of ASD during adulthood, as well as how these relate to behavioral variation, remain poorly understood. To identify brain regions and systems associated with ASD in a large, well-characterized sample of adults. Multicenter case-control design using quantitative magnetic resonance imaging. Medical Research Council UK Autism Imaging Multicentre Study (MRC AIMS), with sites comprising the Institute of Psychiatry, Kings College London; the Autism Research Centre, University of Cambridge; and the Autism Research Group, University of Oxford. Eighty-nine men with ASD and 89 male control participants who did not differ significantly in mean age (26 and 28 years, respectively) and full-scale IQ (110 and 113, respectively). (1) Between-group differences in regional neuroanatomy assessed by voxel-based morphometry and (2) distributed neural systems maximally correlated with ASD, as identified by partial least-squares analysis. Adults with ASD did not differ significantly from the controls in overall brain volume, confirming the results of smaller studies of individuals in this age group without intellectual disability. However, voxelwise comparison between groups revealed that individuals with ASD had significantly increased gray matter volume in the anterior temporal and dorsolateral prefrontal regions and significant reductions in the occipital and medial parietal regions compared with controls. These regional differences in neuroanatomy were significantly correlated with the severity of specific autistic symptoms. The large-scale neuroanatomic networks maximally correlated with ASD identified by partial least-squares analysis included the regions identified by voxel-based analysis, as well as the cerebellum, basal ganglia, amygdala, inferior parietal lobe, cingulate cortex, and various medial, orbital, and lateral prefrontal regions. We also observed spatially distributed reductions in white matter volume in participants with ASD. Adults with ASD have distributed differences in brain anatomy and connectivity that are associated with specific autistic features and traits. These results are compatible with the concept of autism as a syndrome characterized by atypical neural "connectivity."


A simple quantum statistical thermodynamics interpretation of an impressive phase diagram pressure shift upon (H/D) isotopic substitution in water + 3-methylpyridine.
In a previous work (J. Phys. Chem. B 2003, 107, 9837), we reported liquid-liquid-phase splitting at negative pressures in mixtures of H2O + D2O + 3-methylpyridine (3-MP) at the limit of pure H2O as the solvent, thus extending for the first time the L-L phase diagrams to this metastable region. We showed that there is an intimate relation between pressure and solvent deuterium content. Isotopic substitution (H/D) in water provokes subtle entropic effects that, in turn, trigger a significant pressure shift, opening a pressure-wide miscibility window of as much as 1600 bar. Isotope effects are quantum in origin. Therefore, a model that is both pressure-dependent and considers quantization constitutes a necessary tool if one wishes to fully describe the p, T, x critical demixing in these systems. In the current work, the statistical-mechanical theory of isotope effects is combined with a compressible pressure-dependent model. This combination enabled us to predict successfully the overall L-L phase diagram via differences in the vibrational mode frequencies of water on its transfer from the pure state to that of dilution in 3-MP: each of the three librational modes undergo a calculated red-shift of -(250 +/- 30) cm(-1), while the overall internal frequencies contribution is estimated as a total +(400 +/- 25) cm(-1) blue-shift.


Genetic diversity among Borrelia strains determined by single-strand conformation polymorphism analysis of the ospC gene and its association with invasiveness.
Lyme borreliosis (LB) is a tick-borne spirochetal infection caused by three Borrelia species: Borrelia afzelii, B. garinii, and B. burgdorferi sensu stricto. LB evolves in two stages: a skin lesion called erythema migrans and later, different disseminated forms (articular, neurological, cardiac.). Previous research based on analysis of ospC sequences allowed the definition of 58 groups (divergence of <2% within a group and >8% between groups). Only 10 of these groups include all of the strains isolated from disseminated forms that are considered invasive. The aim of this study was to determine whether or not invasive strains belong to restricted ospC groups by testing human clinical strains isolated from disseminated forms. To screen for ospC genetic diversity, we used single-strand conformation polymorphism (SSCP) analysis. Previously known ospC sequences from 44 different strains were first tested, revealing that each ospC group had a characteristic SSCP pattern. Therefore, we studied 80 disseminated-form isolates whose ospC sequences were unknown. Of these, 28 (35%) belonged to previously known invasive groups. Moreover, new invasive groups were identified: six of B. afzelii, seven of B. garinii, and one of B. burgdorferi sensu stricto. This study confirmed that invasive strains are not distributed among all 69 ospC groups but belong to only 24 groups. This suggests that OspC may be involved in the invasiveness of B. burgdorferi.


New Perspectives on the Neuropathology in Huntington's Disease in the Human Brain and its Relation to Symptom Variation.
We review recent investigations regarding the relationship between selective neurodegeneration in the human brain and the variability in symptom profiles in Huntington's disease. Huntington's disease is a genetic neurodegenerative disorder caused by an expanded CAG repeat in exon 1 of the Huntingtin gene on chromosome 4, encoding a protein called huntingtin. The huntingtin protein is expressed ubiquitously in somatic tissue, however, the major pathology affects the brain with profound degeneration in the striatum and the cerebral cortex. Despite the disease being caused by a single gene, there is a major variability in the neuropathology, as well as major heterogeneity in the symptom profiles observed in Huntington's disease patients. The symptoms may vary throughout the disease course and present as varying degrees of movement disorder, cognitive decline, and mood and behavioral changes. To determine whether there is an anatomical basis underlying symptom variation, recent studies on the post-mortem human brain have shown a relationship between the variable degeneration in the forebrain and the variable symptom profile. In this review, we will summarize the progress relating cell loss in the striatum and cerebral cortex to symptom profile in Huntington's disease.


Evaluating Treatments and Spray Application for the Protection of Grapevine Pruning Wounds from Infection by Eutypa lata.
Eutypa dieback threatens the sustainability of vineyards worldwide and limited treatments are available for control of the disease in grapevine. Following the loss of the effective benzimidazole fungicides, benomyl and carbendazim, there is a need to identify alternatives for the protection of pruning wounds against infection by ascospores of Eutypa lata. In this study, 24 fungicide and natural treatments were evaluated in the laboratory and field. Tebuconazole and carbendazim were the most effective fungicides for reducing colonization of pruning wounds inoculated with E. lata. Pyrimethanil and fluazinam also provided some control but were less effective than tebuconazole at the rates tested. Other treatments, such as cyprodinil + fludioxionil, pyraclostrobin, a garlic extract, and lactoferrin, reduced colonization of wounds by E. lata but require further evaluation at higher concentrations. Carbendazim applied to pruning wounds using tractor-driven sprayers reduced the incidence of pruning wound infection by E. lata to levels similar to that achieved by application with a paint brush.


The limited efficacy of methotrexate, actinomycin D and cisplatin (MAP) for patients with advanced testicular cancer.
Combination chemotherapy of methotrexate, actinomycin D and cisplatin (MAP) is reported to be effective against gestational choriocarcinoma. Eight patients with metastatic testicular cancer who had elevated beta-hCG were treated with MAP. They included three refractory cases and two relapsed cases. An additional three patients received MAP as part of the induction therapy. The MAP therapy consisted of methotrexate (10 mg/m2) on days 1-5, actinomycin D (0.01 mg/kg) on days 1-5 and cisplatin (70 mg/m2) on day 1. In all three refractory patients, MAP failed to achieve tumor marker normalization. However, the elevated tumor markers normalized after MAP in the two cases of relapse. Of these two, one patient relapsed again 7 months after MAP and was subsequently salvaged with high-dose chemotherapy. The other patient relapsed and died of the disease 30 months after receiving MAP. Of the three patients who received MAP as part of the induction chemotherapy, one with pure choriocarcinoma achieved tumor marker normalization after MAP and is still alive without disease progression. In the other two patients, MAP failed to achieve marker normalization and the patients received high-dose chemotherapy. The toxicities were mainly bone marrow suppression and mucositis, which were almost acceptable. The results demonstrated the limited efficacy of MAP as salvage therapy. In addition, the efficacy of MAP as part of induction chemotherapy was negligible. However, there might be some role for MAP as a salvage therapy for patients with pure choriocarcinoma.


Transmissible mitochondrial hypovirulence in a natural population of Cryphonectria parasitica.
A cytoplasmically transmissible hypovirulence syndrome has been identified in virus-free strains of the chestnut blight fungus Cryphonectria parasitica isolated from healing cankers on American chestnut trees in southwestern Michigan. The syndrome is associated with symptoms of fungal senescence, including a progressive decline in the growth potential and abundance of conidia, and elevated levels of respiration through the cyanide-insensitive alternative oxidase pathway. Conidia from senescing mycelia exhibited varying degrees of senescence ranging from normal growth to death soon after germination. Cytoplasmic transmission of hypovirulence between mycelia occurred by hyphal contact and coincided with the transfer of a specific restriction fragment length polymorphism from the mitochondrial DNA (mtDNA) of the donor strains into the mtDNA of virulent recipients. The transmission of the senescence phenotype was observed not only among vegetatively compatible strains but also among incompatible strains. Hypovirulence was present in isolates from the same location with different nuclear genotypes as identified by DNA fingerprinting. This study confirms that mitochondrial hypovirulence can occur spontaneously and spread within a natural population of a phytopathogenic fungus.


Genetic selection for temperament traits in dairy and beef cattle.
Animal temperament can be defined as a response to environmental or social stimuli. There are a number of temperament traits in cattle that contribute to their welfare, including their response to handling or milking, response to challenge such as human approach or intervention at calving, and response to conspecifics. In a number of these areas, the genetic basis of the trait has been studied. Heritabilities have been estimated and in some cases quantitative trait loci (QTL) have been identified. The variation is sometimes considerable and moderate heritabilities have been found for the major handling temperament traits, making them amenable to selection. Studies have also investigated the correlations between temperament and other traits, such as productivity and meat quality. Despite this, there are relatively few examples of temperament traits being used in selection programmes. Most often, animals are screened for aggression or excessive fear during handling or milking, with extreme animals being culled, or EBVs for temperament are estimated, but these traits are not commonly included routinely in selection indices, despite there being economic, welfare and human safety drivers for their. There may be a number of constraints and barriers. For some traits and breeds, there may be difficulties in collecting behavioral data on sufficiently large populations of animals to estimate genetic parameters. Most selection indices require estimates of economic values, and it is often difficult to assign an economic value to a temperament trait. The effects of selection primarily for productivity traits on temperament and welfare are discussed. Future opportunities include automated data collection methods and the wider use of genomic information in selection.


Seroprevalence of Q Fever in Patients Undergoing Heart Valve Replacement Surgery.
Q fever, caused by the rickettsia Coxiella burnetii, is a worldwide zoonotic disease with both acute and chronic manifestations. Endocarditis is the principal chronic manifestation. Q fever can easily be mistaken for degenerative valve disease due to its indolent presentation, the fastidious nature of the organism (routine cultures are negative), and the absence of a typical echocardiographic and macroscopic appearance for endocarditis. Prosthetic valve failure, with associated morbidity and mortality, have been described following unrecognized infections. Previous studies have documented the value of screening strategies in areas of high prevalence. Hence, a pilot study was conducted in a low-prevalence setting, in which 139 patients at two tertiary cardiac centers attending for elective valve replacement for degenerative valvular disease underwent testing for chronic Q fever infection by serological and molecular methods on blood and valve tissue. Five patients (3.7%) had serological evidence of past exposure to Q fever (consistent with rates in the literature). None had evidence of chronic Q fever endocarditis. The cost of adopting a universal screening strategy is around £40,000 per case (if serology is used to screen patients prior to surgery). Alternative and more cost-effective methods for identifying clinically quiet cases of chronic Q fever endocarditis are required.


Taking advantage of selective change driven processing for 3D scanning.
This article deals with the application of the principles of SCD (Selective Change Driven) vision to 3D laser scanning. Two experimental sets have been implemented: one with a classical CMOS (Complementary Metal-Oxide Semiconductor) sensor, and the other one with a recently developed CMOS SCD sensor for comparative purposes, both using the technique known as Active Triangulation. An SCD sensor only delivers the pixels that have changed most, ordered by the magnitude of their change since their last readout. The 3D scanning method is based on the systematic search through the entire image to detect pixels that exceed a certain threshold, showing the SCD approach to be ideal for this application. Several experiments for both capturing strategies have been performed to try to find the limitations in high speed acquisition/processing. The classical approach is limited by the sequential array acquisition, as predicted by the Nyquist-Shannon sampling theorem, and this has been experimentally demonstrated in the case of a rotating helix. These limitations are overcome by the SCD 3D scanning prototype achieving a significantly higher performance. The aim of this article is to compare both capturing strategies in terms of performance in the time and frequency domains, so they share all the static characteristics including resolution, 3D scanning method, etc., thus yielding the same 3D reconstruction in static scenes.


Modified Stoppa approach for operative treatment of acetabular fractures: 10-year experience and mid-term follow-up.
The (modified) Stoppa approach for acetabular fracture surgery has gained significant popularity and early results have been encouraging but clinical outcome at extensive follow-up is scarce. The purpose of this study is to provide an update on our experience with this approach for operative treatment of acetabular fractures and to assess clinical outcome at mid-term follow-up. In this retrospective study, all patients treated operatively for an acetabular fracture using the Stoppa approach over a 10-year period were included. Surgery details were reviewed and patients were contacted and requested to return for follow-up. Primary outcome was native hip survivorship, secondary outcome measures included; functional outcome (Merle d'Aubiginé, Harris hip) scores, health-related quality of life (short-form 36) and radiographic outcome (heterotopic ossification, hip osteoarthritis). Forty-five patients received operative fixation for 47 acetabular fractures using the Stoppa approach. Complications requiring surgical intervention were found in one patient (with a vascular lesion) intra-operatively and 3 patients (with wound infections (2) and diffuse bleeding (1)) post-operatively. Follow-up was 83% and 29/39 (74%) native hips survived at mean 59 months (SD 49) postoperatively. Excellent-good functional scores were found in 88% (Merle d'Aubiginé) and 76% (Harris hip) of patients who had retained their native hip. Most (6/8) short-form 36 indices in these patients were comparable to population norms. Of 29 native hips with radiographic follow-up (mean 59 months (SD 49), 4 (86%) had no-minimal radiographic abnormalities. This study confirms that the Stoppa approach is a safe and effective technique for acetabular fracture fixation. Moreover, at mid-term follow-up, this approach is associated with satisfactory results in terms of hip survivorship as well as functional and radiographic outcome. As such, our findings reinforce the notion that this less invasive technique presents a valuable alternative to the ilioinguinal approach for the surgical treatment of acetabular fractures.


Soluble factors from IL-1β-stimulated astrocytes activate NR1a/NR2B receptors: implications for HIV-1-induced neurodegeneration.
Astrocytes play an important role in astrocyte-neuron homeostasis. In HIV-1-infected brain, interleukin 1 beta (IL-1β) activation of astrocytes contributes to neurodegeneration. However, the molecular mechanisms underlying IL-1β-activated-astrocytes-induced neurodegeneration in HIV-1-infected brain are largely unknown. We hypothesize that secretory factors from the activated astrocytes affect N-methyl-d-aspartate (NMDA) receptor, a major pathway implicated in HIV-1-associated neurodegeneration. To test this hypothesis, we studied effects of IL-1β-stimulated astrocyte conditioned medium (ACM+) for its ability to activate NR1a/NR2B receptors expressed on Xenopus oocytes. Astrocytes treated with IL-1β 20ng/ml for 24h induced CXCL8, CCL2, MMP1 and MMP7. Pressure ejection of the ACM(+) produced an inward current in NR1a/NR2B-expressing oocytes. The inward current produced by ACM(+) was blocked by NMDA receptor antagonist, APV but not by non-NMDA receptor antagonist, CNQX. These results suggest that IL-1β stimulated astrocytes activate NR1a/NR2B receptors which may have implications in HIV-1-associated neurodegeneration.


Covalent organic framework-supported platinum nanoparticles as efficient electrocatalysts for water reduction.
The hydrogen evolution reaction (HER) is one of the most effective and sustainable ways to produce hydrogen gas as an alternative clean fuel. The rate of this electrocatalytic reaction is highly dependent on the properties (dispersity and stability) of electrocatalysts. Herein, we developed well-dispersed and highly stable platinum nanoparticles (PtNPs) supported on a covalent organic framework (COF-bpyTPP), which exhibit excellent catalytic activities toward HER as well as the hydride reduction reaction. The nanoparticles have an average size of 2.95 nm and show superior catalytic performance compared to the commercially available Pt/C under the same alkaline conditions, producing 13 times more hydrogen with a far more positive onset potential (-0.13 V vs.-0.63 V) and ca. 100% faradaic efficiency. The reaction rate of the hydride reduction of 4-nitrophenol was also 10 times faster in the case of PtNPs@COF compared to the commercial Pt/C under the same loading and conditions. More importantly, the PtNPs@COF are highly stable under the aqueous reactions conditions and can be reused without showing noticeable aggregation and activity degradation.


Bury My Documents in Lenexa, Kansas: Expert Witness Work and the American Indian Records Repository.
Restricted access to the American Indian Records Repository (AIRR) poses significant problems for expert witness historians working outside the federal government, as well as for academic historians and tribes. The authors discuss the creation of the AIRR in 2004, the records housed there, and the challenges they have experienced as expert witnesses seeking access to the AIRR. Although the AIRR preserves a far greater volume of federal records than might have otherwise occurred, the lack of public access may ultimately impede historians' ability to examine modern topics in Native American history and United States-tribal relations.


CFS-1686 causes cell cycle arrest at intra-S phase by interference of interaction of topoisomerase 1 with DNA.
CFS-1686 (chemical name (E)-N-(2-(diethylamino)ethyl)-4-(2-(2-(5-nitrofuran-2-yl)vinyl)quinolin-4-ylamino)benzamide) inhibits cell proliferation and triggers late apoptosis in prostate cancer cell lines. Comparing the effect of CFS-1686 on cell cycle progression with the topoisomerase 1 inhibitor camptothecin revealed that CFS-1686 and camptothecin reduced DNA synthesis in S-phase, resulting in cell cycle arrest at the intra-S phase and G1-S boundary, respectively. The DNA damage in CFS-1686 and camptothecin treated cells was evaluated by the level of ATM phosphorylation, γH2AX, and γH2AX foci, showing that camptothecin was more effective than CFS-1686. However, despite its lower DNA damage capacity, CFS-1686 demonstrated 4-fold higher inhibition of topoisomerase 1 than camptothecin in a DNA relaxation assay. Unlike camptothecin, CFS-1686 demonstrated no activity on topoisomerase 1 in a DNA cleavage assay, but nevertheless it reduced the camptothecin-induced DNA cleavage of topoisomerase 1 in a dose-dependent manner. Our results indicate that CFS-1686 might bind to topoisomerase 1 to inhibit this enzyme from interacting with DNA relaxation activity, unlike campothecin's induction of a topoisomerase 1-DNA cleavage complex. Finally, we used a computer docking strategy to localize the potential binding site of CFS-1686 to topoisomerase 1, further indicating that CFS-1686 might inhibit the binding of Top1 to DNA.


Structural and Ultrastructural Alterations in Human Olfactory Pathways and Possible Associations with Herpesvirus 6 Infection.
Structural and ultrastructural alterations in human olfactory pathways and putative associations with human herpesvirus 6 (HHV-6) infection were studied. The olfactory bulb/tract samples from 20 subjects with an unspecified encephalopathy determined by pathomorphological examination of the brain autopsy, 17 healthy age-matched and 16 younger controls were used. HHV-6 DNA was detected in 60, 29, and 19% of cases in these groups, respectively. In the whole encephalopathy group, significantly more HHV-6 positive neurons and oligodendrocytes were found in the gray matter, whereas, significantly more HHV-6 positive astrocytes, oligodendrocytes, microglia/macrophages and endothelial cells were found in the white matter. Additionally, significantly more HHV-6 positive astrocytes and, in particular, oligodendrocytes were found in the white matter when compared to the gray matter. Furthermore, when only HHV-6 PCR+ encephalopathy cases were studied, we observed similar but stronger associations between HHV-6 positive oligodendrocytes and CD68 positive cells in the white matter. Cellular alterations were additionally evidenced by anti-S100 immunostaining, demonstrating a significantly higher number of S100 positive cells in the gray matter of the whole encephalopathy group when compared to the young controls, and in the white matter when compared to both control groups. In spite the decreased S100 expression in the PCR+ encephalopathy group when compared to PCR- cases and controls, groups demonstrated significantly higher number of S100 positive cells in the white compared to the gray matter. Ultrastructural changes confirming the damage of myelin included irregularity of membranes and ballooning of paranodal loops. This study shows that among the cellular targets of the nervous system, HHV-6 most severely affects oligodendrocytes and the myelin made by them.


Long-term humoral and cellular immune responses elicited by a heterologous Plasmodium vivax apical membrane antigen 1 protein prime/adenovirus boost immunization protocol.
Apical membrane antigen 1 (AMA-1) is an invasion-related Plasmodium antigen that is expressed during both intracellular and extracellular asexual stages of the parasite's life cycle, making it an ideal target for induction of humoral and cellular immune responses that can protect against malaria. We show here that when it is administered as a recombinant protein (P) in Montanide ISA720 adjuvant, followed by a recombinant human type 5 adenovirus (Ad), intense and long-lasting Plasmodium vivax AMA-1-specific antibody responses (including both IgG1 and IgG2a), as well as proliferative memory T cell responses, can be detected in immunized mice. Memory T cells displayed both central (CD44(hi) CD62L(hi)) and effector (CD44(hi) CD62L(lo)) phenotypes, with the central memory phenotype prevailing (56% of AMA-1-specific proliferating cells). Considering the main traits of the memory immune responses induced against AMA-1, this particular sequence of immunogens (P followed by Ad), but no others (Ad/Ad, Ad/P, or P/P), displayed an optimal synergistic effect. These results give further support to the need for preclinical studies of P. vivax vaccine candidate AMA-1 administered in prime/boost protocols that include recombinant proteins and adenoviral vectors.


American Diabetes Association diabetes diagnostic criteria, advancing age, and cardiovascular disease risk profiles: results from the Third National Health and Nutrition Examination Survey.
To evaluate age-specific effects on diabetes prevalence estimates resulting from the American Diabetes Association (ADA) recommendation against use of the oral glucose tolerance test (OGTT), we contrasted the prevalence of two mutually exclusive groups: undiagnosed diabetes according to ADA criteria (no report of diabetes and fasting glucose [FG] > or =126 mg/dl) and isolated postchallenge hyperglycemia (IPH) (FG <126 mg/dl and OGTT > or =200 mg/dl), a group designated to have diabetes by World Health Organization (WHO) criteria but not ADA criteria. The weighted age-specific ratios of undiagnosed diabetes:IPH were calculated for 2,844 subjects aged 40-74 years without reported diabetes who had both FG and OGTT. A ratio > 1.0 indicated that the proportion of undiagnosed diabetes was greater than that of IPH. Mean levels of HbA1c and cardiovascular disease (CVD) risk factors were contrasted among people with undiagnosed diabetes and IPH and those without either abnormality ("nondiabetic"). Both undiagnosed diabetes and IPH increased with age, but age-specific undiagnosed diabetes:IPH ratios decreased from 5.49 in the 40-44 age-group to 0.77 in the 70-74 age-group. Regression analysis showed a significant (P = 0.006) negative association between age and these ratios. Mean HbA1c was 7.1% in the undiagnosed diabetes group and differed significantly from that of the IPH and nondiabetic groups (5.6 and 5.3%, respectively). Individuals with undiagnosed diabetes had less favorable triglycerides, BMI, and HDL cholesterol compared with people with IPH. Compared with WHO criteria, the ADA criteria underestimate glucose abnormalities more with increasing age. However, compared to those with undiagnosed diabetes, individuals with IPH had a mean HbA1c level that is considered in the nondiabetic range, and this group had significantly more favorable levels of several key CVD risk factors. These findings suggest that the ADA criteria, although underestimating the abnormalities of postchallenge hyperglycemia that occur frequently with increasing age, appear to be effective at identifying a group of individuals with both unfavorable CVD risk factor profiles and evidence of long-term exposure to hyperglycemia.


Antihyperglycemic effect of the alcoholic seed extract of Swietenia macrophylla on streptozotocin-diabetic rats.
Streptozotocin (STZ) selectively destroys the pancreatic insulin secreting cells, leaving less active cells and resulting in a diabetic state. The present study was designed to investigate the antihyperglycemic effect of the ethanolic seed extract of Swietenia macrophylla (SME) in normal and STZ-diabetic rats. The experimental groups were rendered diabetic by intraperitoneal injection of a single dose of STZ (40 mg/kg body weight [BW]). Rats with glucose levels > 200 mg/dL were considered diabetic and were divided into 5 groups. Three groups of diabetic animals were orally administered, daily with seed extract at a dosage of 50, 100, and 200 mg/kg BW. One group of STZ rats was treated as diabetic control and the other group was orally administered 600 μg/kg BW glibenclamide daily. Graded doses of seed extract and glibenclamide showed a significant reduction in blood glucose levels and improvement in serum insulin levels. The extract also improved body weight and promoted liver glycogen content. After treatment, hemoglobin (Hb) level increased and glycosylated Hb level significantly decreased in diabetic rats. The activities of the carbohydrate metabolic enzymes showed significant changes in the rats. Of the 3 doses, 100 mg dose showed maximum activity. Histological investigations of pancreas also supported the biochemical findings. Thus, our findings indicate the folklore use of the seed for diabetes and the mechanism seems to be insulin secretion.


In-hospital mortality after resection of biliary tract cancer in the United States.
To assess perioperative mortality following resection of biliary tract cancer within the U.S. Resection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies. Using the Nationwide Inpatient Sample 1998-2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection. 31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age >/=50 (vs. <50; age 50-59 odds ratio [OR] 5.51, 95% confidence interval [CI] 1.70-17.93; age 60-69 OR 7.25, 95% CI 2.29-22.96; age >/= 70 OR 9.03, 95% CI 2.86-28.56), the presence of identified comorbidities (congestive heart failure, OR 3.67, 95% CI 2.61-5.16; renal failure, OR 4.72, 95% CI 2.97-7.49), and admission designated as emergent (vs. elective; OR 1.82, 95% CI 1.39-2.37). Increased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection.


Genetic consequences of polygyny and social structure in an Indian fruit bat, Cynopterus sphinx. II. Variance in male mating success and effective population size.
Variance in reproductive success is a primary determinant of genetically effective population size (Ne), and thus has important implications for the role of genetic drift in the evolutionary dynamics of animal taxa characterized by polygynous mating systems. Here we report the results of a study designed to test the hypothesis that polygynous mating results in significantly reduced Ne in an age-structured population. This hypothesis was tested in a natural population of a harem-forming fruit bat, Cynopterus sphinx (Chiroptera: Pteropodidae), in western India. The influence of the mating system on the ratio of variance Ne to adult census number (N) was assessed using a mathematical model designed for age-structured populations that incorporated demographic and genetic data. Male mating success was assessed by means of direct and indirect paternity analysis using 10-locus microsatellite genotypes of adults and progeny from two consecutive breeding periods (n = 431 individually marked bats). Combined results from both analyses were used to infer the effective number of male parents in each breeding period. The relative proportion of successfully reproducing males and the size distribution of paternal sibships comprising each offspring cohort revealed an extremely high within-season variance in male mating success (up to 9.2 times higher than Poisson expectation). The resultant estimate of Ne/N for the C. sphinx study population was 0.42. As a result of polygynous mating, the predicted rate of drift (1/2Ne per generation) was 17.6% higher than expected from a Poisson distribution of male mating success. However, the estimated Ne/N was well within the 0.25-0.75 range expected for age-structured populations under normal demographic conditions. The life-history schedule of C. sphinx is characterized by a disproportionately short sexual maturation period scaled to adult life span. Consequently, the influence of polygynous mating on Ne/N is mitigated by the extensive overlap of generations. In C. sphinx, turnover of breeding males between seasons ensures a broader sampling of the adult male gamete pool than expected from the variance in mating success within a single breeding period.


Metabolic markers in sports medicine.
Physical exercise induces adaptations in metabolism considered beneficial for health. Athletic performance is linked to adaptations, training, and correct nutrition in individuals with genetic traits that can facilitate such adaptations. Intense and continuous exercise, training, and competitions, however, can induce changes in the serum concentrations of numerous laboratory parameters. When these modifications, especially elevated laboratory levels, result outside the reference range, further examinations are ordered or participation in training and competition is discontinued or sports practice loses its appeal. In order to correctly interpret commonly used laboratory data, laboratory professionals and sport physicians need to know the behavior of laboratory parameters during and after practice and competition. We reviewed the literature on liver, kidney, muscle, heart, energy, and bone parameters in athletes with a view to increase the knowledge about clinical chemistry applied to sport and to stimulate studies in this field. In liver metabolism, the interpretation of serum aminotransferases concentration in athletes should consider the release of aspartate aminotransferase (AST) from muscle and of alanine aminotransferase (ALT) mainly from the liver, when bilirubin can be elevated because of continuous hemolysis, which is typical of exercise. Muscle metabolism parameters such as creatine kinase (CK) are typically increased after exercise. This parameter can be used to interpret the physiological release of CK from muscle, its altered release due to rhabdomyolysis, or incomplete recovery due to overreaching or trauma. Cardiac markers are released during exercise, and especially endurance training. Increases in these markers should not simply be interpreted as a signal of cardiac damage or wall stress but rather as a sign of regulation of myocardial adaptation. Renal function can be followed in athletes by measuring serum creatinine concentration, but it should be interpreted considering the athlete's body-mass index (BMI) and phase of the competitive season; use of cystatin C could be a reliable alternative to creatinine. Exercise and training induce adaptations in glucose metabolism which improve glucose utilization in athletes and are beneficial for reducing insulin insensitivity in nonathletes. Glucose metabolism differs slightly for different sports disciplines, as revealed in laboratory levels. Sport activities induce a blood lipid profile superior to that of sedentary subjects. There are few reports for a definitive conclusion, however. The differences between athletes and sedentary subjects are mainly due to high-density lipoprotein cholesterol (HDLC) concentrations in physically active individuals, although some differences among sport disciplines exist. The effect of sports on serum and urinary markers for bone metabolism is not univocal; further studies are needed to establish the real and effective influence of sport on bone turnover and especially to establish its beneficial effect.


Structure of the N-terminal domain of the circadian clock-associated histidine kinase SasA.
Circadian oscillators are endogenous biological systems that generate the approximately 24 hour temporal pattern of biological processes and confer a reproductive fitness advantage to their hosts. The cyanobacterial clock is the simplest known and the only clock system for which structural information for core component proteins, in this case KaiA, KaiB and KaiC, is available. SasA, a clock-associated histidine kinase, is necessary for robustness of the circadian rhythm of gene expression and implicated in clock output. The N-terminal domain of SasA (N-SasA) interacts directly with KaiC and likely functions as the sensory domain controlling the SasA histidine kinase activity. N-SasA and KaiB share significant sequence similarity and, thus, it has been proposed that they would be structurally similar and may even compete for KaiC binding. Here, we report the NMR structure of N-SasA and show it to be different from that of KaiB. The structural comparisons provide no clear details to suggest competition of SasA and KaiB for KaiC binding. N-SasA adopts a canonical thioredoxin fold but lacks the catalytic cysteine residues. A patch of conserved, solvent-exposed residues is found near the canonical thioredoxin active site. We suggest that this surface is used by N-SasA for protein-protein interactions. Our analysis suggests that the structural differences between N-SasA and KaiB are the result of only a few critical amino acid substitutions.


Heavy metal speciation in solid-phase materials from a bacterial sulfate reducing bioreactor using sequential extraction procedure combined with acid volatile sulfide analysis.
Heavy metal mobility, bioavailability and toxicity depends largely on the chemical form of metals and ultimately determines potential for environmental pollution. For this reason, determining the chemical form of heavy metals and metalloids, immobilized in sludges by biological mediated sulfate reduction, is important to evaluate their mobility and bioavailability. A modified Tessier sequential extraction procedure (SEP), complemented with acid volatile sulfide (AVS) and simultaneous extracted metals (SEM) measurements, were applied to determine the partitioning of five heavy metals (defined as Fe, Ni, Zn and Cu, and the metalloid As) in anoxic solid-phase material (ASM) from an anaerobic, sulfate reducing bioreactor into six operationally defined fractions. These fractions were water soluble, exchangeable, bound to carbonates (acid soluble), bound to Fe-Mn oxides (reducible), bound to organic matter and sulfides (oxidizable) and residual. It was found that the distribution of Fe, Ni, Zn, Cu and As in ASM was strongly influenced by its association with the above solid fractions. The fraction corresponding to organic matter and sulfides appeared to be the most important scavenging phases of As, Fe, Ni, Zn and Cu in ASM (59.8-86.7%). This result was supported by AVS and SEM (Sigma Zn, Ni and Cu) measurements, which indicated that the heavy metals existed overwhelmingly as sulfides in the organic matter and sulfide fraction. A substantial amount of Fe and Ni at 16.4 and 20.1%, respectively, were also present in the carbonate fraction, while an appreciable portion of As (18.3%) and Zn (19.4%) was bound to Fe-Mn oxides. A significant amount of heavy metals was also associated with the residual fraction, ranging from 2.1% for Zn to 18.8% for As. Based on the average total extractable heavy metal (TEHM) values, the concentration of heavy metals in the ASM was in the order of Cu > Ni > Zn > Fe > As. If the mobility and bioavailability of heavy metals are assumed to be related to their solubility and chemical forms, and that they decrease with each successive extraction step, then the apparent mobility and bioavailability of these five heavy metals in ASM increase in the order of Cu < As < Ni < Fe < Zn. The SEM/AVS ratio was less than one in eight replicate ASM samples, indicating that the ASM was non-toxic with regards to having a low probability of bioavailable metals in the pore water.


Toxicity of forest fire retardant chemicals to stream-type chinook salmon undergoing parr-smolt transformation.
Long-term fire retardants are used to prevent the spread of wildland fires. These products are normally applied by aircraft and are intended specifically for terrestrial application, but fire retardants have entered aquatic habitats by misapplication and/or accidental spills and have resulted in fish mortalities. The authors examined the toxicity of two fire retardant products, PHOS-CHEK 259F and LC-95A, to salmon undergoing parr-smolt transformation. Yearling stream-type chinook salmon at the smolt stage were exposed to eight concentrations of each retardant in freshwater and a no-PHOS-CHEK control for 96 h to determine acute toxicity. Concentrations of the products that caused 50% mortality were 140.5 and 339.8 mg/L for 259F and LC-95A, respectively, and could occur during accidental drops into aquatic habitats. Damage to gill tissues seen in histopathological sections was attributed to fire retardant exposure. Un-ionized ammonia levels, from 259F, were sufficient to cause acute mortality; but additional factors, indicated by increased phagosome prevalence in the gills, might have contributed to mortality during LC-95A exposure. Seawater and disease challenges were performed to determine sublethal effects of product exposures on fish health. Although PHOS-CHEK exposure did not adversely affect chinook salmon's susceptibility to Listonella anguillarum, exposure did significantly reduce seawater survival. Reduced salmon survival resulting from prior fire retardant exposure during their transition from freshwater rearing environments to seawater may decrease the abundance of salmon populations.


Examining the Pathways between Gratitude and Self-Rated Physical Health across Adulthood.
The current study examined whether dispositional gratitude predicts physical health among adults, and if so, whether this relationship occurs because grateful individuals lead healthier lives, either psychologically or physically. Specifically, we examined whether psychological health, healthy activities, and willingness to seek help for health concerns mediated the link between gratitude and self-reported physical health, as well as if these mediational pathways are moderated by age, in a broad sample of Swiss adults (N = 962, M(age) = 52 years, age range: 19 to 84). Dispositional gratitude correlated positively with self-reported physical health, and this link was mediated by psychological health, healthy activities, and willingness to seek help for health concerns. However, the indirect effects for psychological health and healthy activities were stronger for older than younger adults. In other words, the mechanisms explaining why gratitude predicts health appear to differ across adulthood.


Long-term Risk of Urinary Adverse Events in Curatively Treated Patients With Rectal Cancer: A Population-Based Analysis.
Treatment modalities for rectal cancer, including radiation, are associated with urinary adverse effects. The purpose of this study was to determine the influence of surgery and radiation therapy for rectal cancer on long-term urinary complications. Using the Surveillance Epidemiology and End Results-Medicare data set from the United States, patients with rectal cancer older than 66 years of age who underwent rectal resection between 1992 and 2007 were stratified into treatment groups that accounted for surgical resection and the timing of radiation therapy, if used. A control group of patients who did not have rectal cancer were matched by age, sex, demographics, and comorbidities. The primary outcome was a urinary adverse event defined as a relevant urinary diagnosis with an associated procedure. Patients with rectal cancer in different treatment groups were compared with control patients using a propensity-adjusted, multivariable Cox regression analysis. The study was conducted with the Surveillance Epidemiology and End Results-Medicare data set from the United States at our institution. Of the 11,068 patients with rectal cancer, 56.2% had surgical resection alone, 21.7% received preoperative radiation, and 22.1% received postoperative radiation. The median follow-up for all of the groups of patients was >2 years. All of the groups of patients with rectal cancer were more likely to develop a urinary adverse event compared with control subjects. Adjusted HRs were 2.28 (95% CI, 2.02-2.57) for abdominoperineal resection alone, 2.24 (95% CI, 1.79-2.80) for preoperative radiation and surgical resection, 2.04 (95% CI, 1.70-2.44) for surgical resection and postoperative radiation, and 1.69 (95% CI, 1.52-1.89) for low anterior resection alone. Treatment patterns are somewhat outdated, with a large proportion of patients receiving postoperative radiation. The data did not allow for accurate assessment of urinary tract infections or mild urinary retention that is not managed with a procedure. Rectal cancer surgery with or without radiation is associated with a higher risk of urinary complications requiring procedures. Patients who undergo low anterior resection without radiation tend toward the lowest risk for a urinary adverse event.


Sensor explication: knowledge-based robotic plan execution through logical objects.
Complex robot tasks are usually described as high level goals, with no details on how to achieve them. However, details must be provided to generate primitive commands to control a real robot. A sensor explication concept that makes details explicit from general commands is presented. We show how the transformation from high-level goals to primitive commands can be performed at execution time and we propose an architecture based on reconfigurable objects that contain domain knowledge and knowledge about the sensors and actuators available. Our approach is based on two premises: 1) plan execution is an information gathering process where determining what information is relevant is a great part of the process; and 2) plan execution requires that many details are made explicit. We show how our approach is used in solving the task of moving a robot to and through an unknown, and possibly narrow, doorway; where sonic range data is used to find the doorway, walls, and obstacles. We illustrate the difficulty of such a task using data from a large number of experiments we conducted with a real mobile robot. The laboratory results illustrate how the proper application of knowledge in the integration and utilization of sensors and actuators increases the robustness of plan execution.


Fifty-year follow-up of childhood epilepsy - Social, psychometric, and occupational outcome.
The objective of this study was to explore and describe the experience of a childhood diagnosis of epilepsy and its consequences for the experiences of daily life over a span of 50 years. A descriptive mixed method design was chosen. Data were collected through a survey returned by 86 persons (59% response rate) who had received diagnoses of epilepsy as children. The survey contained questions about education, vocation, family status, and included the 14-item Hospital Anxiety and Depression Scale (HAD). Additionally, interviews (n = 11) were conducted and analyzed by interpretative description. Few persons reported that the childhood diagnosis of epilepsy had affected their choice of education, work, or leisure activities. However, 20% reported that the diagnosis had caused problems in school or at work and had restricted their activities of daily living. Sixty-six percent of the participants were married, and 68% had children; of those, 12 (20%) reported that one or more of the children had also had seizures. Almost all reported no anxiety (82%) and no depression (90%). The results of the interviews revealed a balancing act between 'Controlling and managing the situation' and 'Not being restricted by the condition'. This long-term follow-up over a 50-year life-span of persons who received childhood diagnoses of epilepsy suggests that the consequences for education, work, and leisure activities were few. Most of the participants had developed strategies to manage their situation.


The Arabidopsis RESURRECTION1 gene regulates a novel antagonistic interaction in plant defense to biotrophs and necrotrophs.
We report a role for the Arabidopsis (Arabidopsis thaliana) RESURRECTION1 (RST1) gene in plant defense. The rst1 mutant exhibits enhanced susceptibility to the biotrophic fungal pathogen Erysiphe cichoracearum but enhanced resistance to the necrotrophic fungal pathogens Botrytis cinerea and Alternaria brassicicola. RST1 encodes a novel protein that localizes to the plasma membrane and is predicted to contain 11 transmembrane domains. Disease responses in rst1 correlate with higher levels of jasmonic acid (JA) and increased basal and B. cinerea-induced expression of the plant defensin PDF1.2 gene but reduced E. cichoracearum-inducible salicylic acid levels and expression of pathogenesis-related genes PR1 and PR2. These results are consistent with rst1's varied resistance and susceptibility to pathogens of different life styles. Cuticular lipids, both cutin monomers and cuticular waxes, on rst1 leaves were significantly elevated, indicating a role for RST1 in the suppression of leaf cuticle lipid synthesis. The rst1 cuticle exhibits normal permeability, however, indicating that the disease responses of rst1 are not due to changes in this cuticle property. Double mutant analysis revealed that the coi1 mutation (causing defective JA signaling) is completely epistatic to rst1, whereas the ein2 mutation (causing defective ethylene signaling) is partially epistatic to rst1, for resistance to B. cinerea. The rst1 mutation thus defines a unique combination of disease responses to biotrophic and necrotrophic fungi in that it antagonizes salicylic acid-dependent defense and enhances JA-mediated defense through a mechanism that also controls cuticle synthesis.


Emotional climate, feeding practices, and feeding styles: an observational analysis of the dinner meal in Head Start families.
A number of studies conducted with ethnically diverse, low-income samples have found that parents with indulgent feeding styles had children with a higher weight status. Indulgent parents are those who are responsive to their child's emotional states but have problems setting appropriate boundaries with their child. Because the processes through which styles impact child weight are poorly understood, the aim of this study was to observe differences in the emotional climate created by parents (including affect, tone of voice, and gestures) and behavioral feeding practices among those reporting different feeding styles on the Caregiver's Feeding Styles Questionnaire. A secondary aim was to examine differences on child weight status across the feeding styles. Participants were 177 Head Start families from Houston, Texas (45% African-American; 55% Hispanic). Using an observational approach, the relationship between the observed emotional climate of the meal, behavioral feeding practices, and self-reported parent feeding styles were examined. Mean age of the children was 4.4 years (SD = 0.7) equally distributed across gender. Families were observed on 3 separate dinner occasions. Heights and weight were measured on the parents and children. Parents with self-reported indulgent feeding styles made fewer demands on their children to eat during dinner and showed lower levels of negative affect and intrusiveness. Surprisingly, these parents also showed higher levels of emotional detachment with their children during dinner. Hispanic boys with indulgent parents had significantly higher BMI z scores compared to Hispanic boys in the other three feeding style groups. No other differences were found on child weight status. Results suggest that the emotional climate created by indulgent parents during dinner and their lack of demands on their children to eat may play an important role in how young children become overweight. Numerous observed emotional climate and behavioral differences were found between the other self-reported feeding styles as well. Results suggest that parents' self-reported feeding styles may be a proxy for the emotional climate of the dinner meal, which may in turn influence the child's eating behaviors and weight status.


"Protecting" or "Policing": Academic Researchers' View of IRBs in an Arab Context.
A recent surge of research universities and human subjects research funding in the Arab world raises concerns about applied research ethics and oversight. In-depth interviews conducted with 52 researchers in Lebanon and Qatar about their research conduct and the problems they face while conducting it indicate that although researchers admit to the added value of institutional review board (IRB) functions, the researchers have several complaints, such as rigid and contextually insensitive requirements, delays, and inadequate resources at IRBs, and a lack of outreach and effective communication with researchers. The study discusses these challenges pointing to the need for socioculturally adaptive regulations and forms and strengthening outreach and communication between IRBs and their users to improve ethical practices. Implications for future research are also presented.


Mechanical properties of low-density polyethylene filled by graphite nanoplatelets.
The mechanical properties of GNP/LDPE nanocomposites (graphite nanoplatelets/low density polyethylene) have been investigated, in order to establish the effect of nanoscale reinforcement within the polymer matrix. Results show that the presence of the filler does not involve a change in the microscopic structure of the polymer. However, on a macroscopic scale, GNPs limit the mobility of the polymer chains, resulting in an increase in stiffness for the final composite. Orientation of GNPs within the LDPE matrix is also an important issue that affects mechanical properties and it has been evaluated by testing nanocomposites made by different manufacturing techniques (compression moulding and blown extrusion). The comparison between the experimental data and the Halpin-Tsai model shows that the orientation of GNPs due to the extrusion process leads to values of tensile modulus higher than that obtained with the randomly oriented disposition resulting from the compression moulding technique.


Selection Against Maternal microRNA Target Sites in Maternal Transcripts.
In animals, before the zygotic genome is expressed, the egg already contains gene products deposited by the mother. These maternal products are crucial during the initial steps of development. In Drosophila melanogaster, a large number of maternal products are found in the oocyte, some of which are indispensable. Many of these products are RNA molecules, such as gene transcripts and ribosomal RNAs. Recently, microRNAs (small RNA gene regulators) have been detected early during development and are important in these initial steps. The presence of some microRNAs in unfertilized eggs has been reported, but whether they have a functional impact in the egg or early embryo has not being explored. I have extracted and sequenced small RNAs from Drosophila unfertilized eggs. The unfertilized egg is rich in small RNAs and contains multiple microRNA products. Maternal microRNAs often are encoded within the intron of maternal genes, suggesting that many maternal microRNAs are the product of transcriptional hitchhiking. Comparative genomics analyses suggest that maternal transcripts tend to avoid target sites for maternal microRNAs. I also developed a microRNA target mutation model to study the functional impact of polymorphisms at microRNA target sites. The analysis of Drosophila populations suggests that there is selection against maternal microRNA target sites in maternal transcripts. A potential role of the maternal microRNA mir-9c in maternal-to-zygotic transition is also discussed. In conclusion, maternal microRNAs in Drosophila have a functional impact in maternal protein-coding transcripts.


Macrophage function in tissue repair and remodeling requires IL-4 or IL-13 with apoptotic cells.
Tissue repair is a subset of a broad repertoire of interleukin-4 (IL-4)- and IL-13-dependent host responses during helminth infection. Here we show that IL-4 or IL-13 alone was not sufficient, but IL-4 or IL-13 together with apoptotic cells induced the tissue repair program in macrophages. Genetic ablation of sensors of apoptotic cells impaired the proliferation of tissue-resident macrophages and the induction of anti-inflammatory and tissue repair genes in the lungs after helminth infection or in the gut after induction of colitis. By contrast, the recognition of apoptotic cells was dispensable for cytokine-dependent induction of pattern recognition receptor, cell adhesion, or chemotaxis genes in macrophages. Detection of apoptotic cells can therefore spatially compartmentalize or prevent premature or ectopic activity of pleiotropic, soluble cytokines such as IL-4 or IL-13.


The impact of off-pump coronary artery bypass surgery on postoperative renal function.
A number of risk factors have been recognised for postoperative renal dysfunction following on-pump coronary artery bypass surgery (CABG). There are, however, few studies that have evaluated the potential reno-protective effects of off-pump CABG in the presence of other confounding risk factors. The aim of this study was to determine if off-pump CABG reduces the risk of renal injury. Serum creatinine values (preoperatively and day 1, 2 and 4 postoperatively) and other clinical data were prospectively collected on 1580 consecutive patients who underwent first-time CABG from 2002 to 2005. Creatinine clearance was calculated using the Cockcroft and Gault equation. The effect of on-pump vs. off-pump CABG on renal function was analysed, adjusting for age, gender, diabetes mellitus, left ventricular (LV) function and preoperative creatinine clearance, using multiple regression analysis. One thousand one hundred and forty-five (73%) patients underwent on-pump CABG and 435 (27%) underwent off-pump CABG. The two groups were similar with respect to age, gender and diabetes. Two hundred and seventy-four (17%) patients were females and 274 (17%) patients had diabetes. Multivariate analysis demonstrated significantly lower creatinine clearance postoperatively in patients with diabetes (P<0.001) and advanced age (P<0.001). The on-pump group had significantly lower postoperative creatinine clearance in comparison to the off-pump group (P= 0.01). The effect remained consistent after adjusting for potential risk factors (age, diabetes, gender, LV function and preoperative creatinine clearance) in the multivariate analysis. Off-pump surgery is associated with a reduction in postoperative renal injury.


Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis.
Decisions about the use of killed oral cholera vaccines, which confer moderate levels of direct protection to vaccinees, can depend on whether the vaccines also provide indirect (herd) protection when high levels of vaccine coverage are attained. We reanalysed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from killed oral cholera vaccines. We analysed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse, monotonic trend for the relation between the level of vaccine coverage in a residential cluster and the incidence of cholera in individual vaccine recipients or placebo recipients residing in the cluster after controlling for potential confounding variables. Vaccine coverage of the targeted population ranged from 4% to 65%. Incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (7.01 cases per 1000 in the lowest quintile of coverage vs 1.47 cases per 1000 in the highest quintile; p<0.0001 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's cluster were independently related to a reduced risk of cholera. Moreover, after adjustment for the level of vaccine coverage of the cluster, vaccine protective efficacy remained significant (55% [95% CI 41-66], p<0.0001). In addition to providing direct protection to vaccine recipients, killed oral cholera vaccines confer significant herd protection to neighbouring non-vaccinated individuals. Use of these vaccines could have a major effect on the burden of cholera in endemic settings.


Mate tea (Ilex paraguariensis) promotes satiety and body weight lowering in mice: involvement of glucagon-like peptide-1.
We previously investigated the effects of an aqueous extract of maté (mate) tea, made from the leaves of Ilex paraguariensis, on the diabesity and metabolic syndrome features in a mouse model. Mate induced significant decreases in body weight (BW), body mass index, and food intake (FI). In this study, to verify the mode of action of mate on FI and consequently on BW, we examined the anorexic effects of mate on the appetite and satiety markers glucagon-like peptide 1 (GLP-1) and leptin in high-fat diet-fed ddY mice. GLP-1 is a peptide signal generated by the gastrointestinal tract, which regulates appetite and influences BW, whereas leptin is an afferent signal from the periphery to the brain in a homeostatic feedback loop that regulates adipose tissue mass, thus leading to decreased appetite and FI and increased energy expenditure. Chronic administration of mate (50, 100 mg/kg) for 3 weeks significantly reduced FI, BW, and ameliorated blood fats, liver fats, and adipose tissue. Mate induced significant increases in GLP-1 levels and leptin levels compared with the control. Acute administration of major constituents of mate showed significant increases in GLP-1 levels by dicaffeoyl quinic acids and matesaponins, and significant induction of satiety by caffeoyl quinic acids and caffeine in ddY mice. These findings suggest that mate may induce anorexic effects by direct induction of satiety and by stimulation of GLP-1 secretion and modulation of serum leptin levels.


Mutation signature of adenoid cystic carcinoma: evidence for transcriptional and epigenetic reprogramming.
Adenoid cystic carcinoma (ACC), a relatively rare malignancy usually of salivary gland origin, has a signature v-myb avian myeloblastosis viral oncogene homolog-nuclear factor I/B (MYB-NFIB) gene fusion that activates MYB transcriptional regulatory activity. A new study in this issue by Stephens et al. is a comprehensive genomic mutation profiling analysis of this neoplasm and documents a common theme of alteration in chromatin regulatory genes. Also, mutations in SPEN (split ends, homolog of Drosophila), which encodes an RNA-binding coregulatory protein, suggest that other changes in transcriptional regulation may involve the NOTCH, FGFR, or other signaling pathways in which SPEN participates. Since there is a low prevalence of mutations in common oncogenes and tumor-suppressor genes, it is likely that alterations primarily in specific transcriptional regulatory genes, augmented by changes in chromatin structure, drive the neoplastic process in ACC.


High VEGF-D and Low MMP-2 Serum Levels Predict Nodal-Positive Disease in Invasive Bladder Cancer.
To investigate stromal variables including angiogenesis, lymphangiogenesis, and matrix metalloproteinase (MMP) in the serum of patients with urothelial carcinoma of the bladder (UCB) and to evaluate their association with histopathological characteristics and clinical outcome. Protein levels of vascular endothelial growth factors-A, -C, -D (VEGF-A/-C/-D), their receptors- VEGF-R2 and -R3 (VEGF-R2/-R3), and matrix metalloproteinases 2, -3, and -7 (MMP-2, MMP-3, MMP-7) were quantified in the blood serum samples of 71 patients with UCB before radical cystectomy (RC). Samples of patients with non-invasive UCB or no history of UCB were investigated as controls (n=20). Protein levels in the serum were measured using a flow cytometric cytokine assay. A positive association for VEGF-D (p<0.001) and an inverse association for MMP-2 (p=0.017) were observed in patients with positive lymph node (LN) status at the time of RC. VEGF-A (p<0.001), VEGF-C (p<0.001), MMP-2 (p<0.001), and MMP-7 (p=0.005) serum levels were different in serum of patients with invasive UCB compared with non-invasive UCB or healthy individuals. None of the serum markers were associated with disease progression. High VEGF-D and low MMP-2 serum levels predict LN metastasis in patients with UCB at the time of RC. VEGF-A, VEGF-C, MMP-2, and MMP-7 serum levels varied significantly between invasive and non-invasive disease as well as in comparison with healthy individuals. Clinical implementation of these marker serum measurements may be valuable to select high-risk patients with more invasive or nodal-positive disease.


An impressive capacity for cold tolerance plasticity protects against ionoregulatory collapse in the disease vector Aedes aegypti.
The mosquito Aedes aegypti is largely confined to tropical and subtropical regions, but its range has recently been spreading to colder climates. As insect biogeography is tied to environmental temperature, understanding the limits of A. aegypti thermal tolerance and their capacity for phenotypic plasticity is important in predicting the spread of this species. In this study, we report on the chill coma onset (CCO) and recovery time (CCRT), as well as low-temperature survival phenotypes of larvae and adults of A. aegypti that developed or were acclimated to 15°C (cold) or 25°C (warm). Cold acclimation did not affect CCO temperatures of larvae but substantially reduced CCO in adults. Temperature and the duration of exposure both affected CCRT, and cold acclimation strongly mitigated these effects and increased rates of survival following prolonged chilling. Female adults were far less likely to take a blood meal when cold acclimated, and exposing females to blood (without feeding) attenuated some of the beneficial effects of cold acclimation on CCRT. Lastly, larvae suffered from haemolymph hyperkalaemia when chilled, but cold acclimation attenuated the imbalance. Our results demonstrate that A. aegypti larvae and adults have the capacity to acclimate to low temperatures, and do so at least in part by better maintaining ion balance in the cold. This ability for cold acclimation may facilitate the spread of this species to higher latitudes, particularly in an era of climate change.


Somatosensory Loss Influences the Adoption of Self-Centered Versus Decentered Perspectives.
The body and the self are commonly experienced as forming a unity. Experiencing the external world as distinct from the self and the body strongly relies on adopting a single self-centered perspective which results in integrating multisensory sensations into one egocentric body-centered reference frame. Body posture and somatosensory representations have been reported to influence perception and specifically the reference frame relative to which multisensory sensations are coded. In the study reported here, we investigated the role of somatosensory and visual information in adopting self-centered and decentered spatial perspectives. Two deafferented patients who have neither tactile nor proprioceptive perception below the head and a group of age-matched control participants performed a graphesthesia task, consisting of the recognition of ambiguous letters (b, d, p, and q) drawn tactilely on head surfaces. To answer which letter was drawn, the participants can adopt either a self-centered perspective or a decentered one (i.e., centered on a body part or on an external location). The participants' responses can be used, in turn, to infer the way the left-right and top-bottom letters' axes are assigned with respect to the left-right and top-bottom axes of their body. In order to evaluate the influence of body posture, the ambiguous letters were drawn on the participants' forehead, left, and right surfaces of the head, with the head aligned or rotated in yaw relative to the trunk. In order to evaluate the role of external information, the participants completed the task with their eyes open in one session and closed in another one. The results obtained in control participants revealed that their preferred perspective varied with body posture but not with vision. Different results were obtained with the deafferented patients who overall do not show any significant effect of their body posture on their preferred perspective. This result suggests that the orientation of their self is not influenced by their physical body. There was an effect of vision for only one of the two patients. The deafferented patients rely on strategies that are more prone to interindividual differences, which highlights the crucial role of somatosensory information in adopting self-centered spatial perspectives.


Geographic trends of scientific output and citation practices in psychiatry.
Measures of research productivity are increasingly used to determine how research should be evaluated and funding decisions made. In psychiatry, citation patterns within and between countries are not known, and whether these differ by choice of citation metric. In this study, we examined publication characteristics and citation practices in articles published in 50 Web of Science indexed psychiatric and relevant clinical neurosciences journals, between January 2004 and December 2009 comprising 51,072 records that produced 375,962 citations. We compared citation patterns, including self-citations, between countries using standard x(2) tests. We found that most publications came from the USA, with Germany being second and UK third in productivity. USA articles received most citations and the highest citation rate with an average 11.5 citations per article. The UK received the second highest absolute number of citations, but came fourth by citation rate (9.7 citations/article), after the Netherlands (11.4 citations/article) and Canada (9.8 citations/article). Within the USA, Harvard University published most articles and these articles were the most cited, on average 20.0 citations per paper. In Europe, UK institutions published and were cited most often. The Institute of Psychiatry/Kings College London was the leading institution in terms of number of published records and overall citations, while Oxford University had the highest citation rate (18.5 citations/record). There were no differences between the self-citation practices of American and European researchers. Articles that examined some aspect of treatment in psychiatry were the most published. In terms of diagnosis, papers about schizophrenia-spectrum disorders were the most published and the most cited. We found large differences between and within countries in terms of their research productivity in psychiatry and clinical neuroscience. In addition, the ranking of countries and institutions differed widely by whether productivity was assessed by total research records published, overall citations these received, or citations per paper. The choice of measures of scientific output could be important in determining how research output translates into decisions about resource allocation.


Diet, lifestyle and risk of K-ras mutation-positive and -negative colorectal adenomas.
K-ras mutation-positive (K-ras+) and -negative (K-ras-) colorectal adenomas may differ clinically and pathologically. As environmental compounds may cause mutations in the growth-related K-ras oncogene or affect clonal selection depending on mutational status, we evaluated whether the aetiology of K-ras+ and K-ras- adenomas differs. K-ras mutations in codons 12 and 13 were assessed in colorectal adenoma tissue (K-ras+: n = 81, K-ras-: n = 453). Dietary and lifestyle data were collected through questionnaires that were also administered to 709 polyp-free controls. Multiple logistic regression analyses showed that intake of vitamin B2 and monounsaturated fat were differently associated with risk of K-ras+ and K-ras- adenomas; vitamin B2 was inversely associated with K-ras- (highest vs. lowest tertile: odds ratio (OR) = 0.70, 95% confidence interval (CI) = 0.50-0.97, p trend = 0.020), but not with K-ras+ adenomas, and a positive association with monounsaturated fat was confined to K-ras- adenomas (OR = 1.57, 95% CI = 1.06-2.34, p trend = 0.029). Besides, potential, not statistically significant, differences in risk arose because red meat was distinctly positively associated with K-ras+ adenomas (OR = 1.70, 95% CI = 0.94-3.09, p trend = 0.061); total dietary and polyunsaturated fat tended to be inversely associated with risk of K-ras+ but not of K-ras- adenomas; inverse associations with dairy products, calcium, protein and tea were confined to K-ras- adenomas, and smoking was more markedly positively associated with K-ras- adenomas. No differences in risk of K-ras+ and K-ras- adenomas could be detected for other factors. In conclusion, dietary and lifestyle factors may influence risk of K-ras+ and K-ras- adenomas differently. However, epidemiological literature on diet, lifestyle and colorectal K-ras mutations is inconsistent.


Home-Based Monitor for Gait and Activity Analysis.
Current outcomes in neuromuscular disorder clinical trials include motor function scales, timed tests, and strength measures performed by trained clinical evaluators. These measures are slightly subjective and are performed during a visit to a clinic or hospital and constitute therefore a point assessment. Point assessments can be influenced by daily patient condition or factors such as fatigue, motivation, and intercurrent illness. To enable home-based monitoring of gait and activity, a wearable magneto-inertial sensor (WMIS) has been developed. This device is a movement monitor composed of two very light watch-like sensors and a docking station. Each sensor contains a tri-axial accelerometer, gyroscope, magnetometer, and a barometer that record linear acceleration, angular velocity, the magnetic field of the movement in all directions, and barometric altitude, respectively. The sensors can be worn on the wrist, ankle, or wheelchair to record the subject's movements during the day. The docking station enables data uploading and recharging of sensor batteries during the night. Data are analyzed using proprietary algorithms to compute parameters representative of the type and intensity of the performed movement. This WMIS can record a set of digital biomarkers, including cumulative variables, such as total number of meters walked, and descriptive gait variables, such as the percentage of the most rapid or longest stride that represents the top performance of patient over a predefined period of time.


The relative expression of Mig6 and EGFR is associated with resistance to EGFR kinase inhibitors.
The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence of EGFR tyrosine kinase (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, such as pancreatic and head and neck cancer. In this study we sought to elucidate mechanisms of resistance to EGFR-targeted therapies in tumors that do not harbor TK sensitizing mutations in order to identify markers capable of guiding the decision to incorporate these drugs into chemotherapeutic regimens. Here we show that EGFR activity was markedly decreased during the evolution of resistance to the EGFR tyrosine kinase inhibitor (TKI) erlotinib, with a concomitant increase of mitogen-inducible gene 6 (Mig6), a negative regulator of EGFR through the upregulation of the PI3K-AKT pathway. EGFR activity, which was more accurately predicted by the ratio of Mig6/EGFR, highly correlated with erlotinib sensitivity in panels of cancer cell lines of different tissue origins. Blinded testing and analysis in a prospectively followed cohort of lung cancer patients treated with gefitinib alone demonstrated higher response rates and a marked increased in progression free survival for patients with a low Mig6/EGFR ratio (approximately 100 days, P = 0.01).


Outcomes of anastrozole in oligozoospermic hypoandrogenic subfertile men.
To determine whether the change in sperm parameters in subfertile hypoandrogenic men treated with anastrozole is correlated to the magnitude of increase in testosterone (T) to estrogen ratio in men responding to treatment. Retrospective study. Male fertility clinic. The study group consisted of 86 subfertile hypoandrogenic men with low T/estradiol (E2) ratio (n = 78) or a prior aversive reaction to clomiphene citrate (n = 8). All patients were treated with 1 mg anastrozole daily, administered orally. Hormone analysis and semen analysis before and after treatment were performed. Hormone analysis included measurements of total T, E2, sex-hormone binding globulin, albumin, FSH, and LH, and bioavailable T was calculated. Total motile sperm count was calculated from the semen analysis. In all, 95.3% of patients had an increased serum T and decreased serum E2 after treatment with anastrozole. Sperm concentration and total motile counts improved in 18 of 21 subfertile hypoandrogenic oligozoospermic men treated with anastrozole. In these men the magnitude of total motile count increase was significantly correlated with the change in the T/E2 ratio. No improvement was seen in semen parameters of men with azoospermia, cryptozoospermia, or normozoospermia at presentation. Approximately 95% of men with hypoandrogenism responded with improved endocrine parameters, and a subset of oligozoospermic men (approximately 25% of all patients) displayed significantly improved sperm parameters. In that subset, increase in sperm parameters was correlated with the change in the T/E2 ratio, which argues for a physiologic effect of treatment.


A fast inverse consistent deformable image registration method based on symmetric optical flow computation.
Deformable image registration is widely used in various radiation therapy applications including daily treatment planning adaptation to map planned tissue or dose to changing anatomy. In this work, a simple and efficient inverse consistency deformable registration method is proposed with aims of higher registration accuracy and faster convergence speed. Instead of registering image I to a second image J, the two images are symmetrically deformed toward one another in multiple passes, until both deformed images are matched and correct registration is therefore achieved. In each pass, a delta motion field is computed by minimizing a symmetric optical flow system cost function using modified optical flow algorithms. The images are then further deformed with the delta motion field in the positive and negative directions respectively, and then used for the next pass. The magnitude of the delta motion field is forced to be less than 0.4 voxel for every pass in order to guarantee smoothness and invertibility for the two overall motion fields that are accumulating the delta motion fields in both positive and negative directions, respectively. The final motion fields to register the original images I and J, in either direction, are calculated by inverting one overall motion field and combining the inversion result with the other overall motion field. The final motion fields are inversely consistent and this is ensured by the symmetric way that registration is carried out. The proposed method is demonstrated with phantom images, artificially deformed patient images and 4D-CT images. Our results suggest that the proposed method is able to improve the overall accuracy (reducing registration error by 30% or more, compared to the original and inversely inconsistent optical flow algorithms), reduce the inverse consistency error (by 95% or more) and increase the convergence rate (by 100% or more). The overall computation speed may slightly decrease, or increase in most cases because the new method converges faster. Compared to previously reported inverse consistency algorithms, the proposed method is simpler, easier to implement and more efficient.


Renal denervation prevents sodium retention and hypertension in salt-sensitive rabbits with genetic baroreflex impairment.
1. Rabbits with a genetic impairment in baroreflex control of heart rate become hypertensive on a high salt diet. The present study determined the effect of bilateral renal denervation on blood pressure and sodium balance after salt loading (four times normal intake; 28-36 mEq NaCl/day) in normotensive rabbits with high (Group I) and low (Group II) baroreflex sensitivity, respectively. 2. Eight rabbits in each group were denervated or sham-denervated 1 week before commencement of the high salt diet. Before operation, the two groups differed only in the gain of their cardiac baroreflex (Group I, -6.4 +/- 0.4 beats min-1 mmHg-1; Group II, -3.2 +/- 0.15 beats min-1 mmHg-1). 3. In Group I sham-denervated rabbits, mean arterial pressure remained unchanged, and plasma renin activity and heart rate fell significantly in response to the high salt. In Group II sham-denervated rabbits, mean arterial pressure increased by 10.6 +/- 1.2 mmHg, and heart rate and plasma renin activity remained unchanged. Their cumulative Na+ retention and weight gain was more than twice that of Group I sham-denervated rabbits. 4. Renal denervation decreased plasma renin activity in both groups to < 1 pmol Ang I h-1 ml-1, lowered cumulative Na+ retention from 102 +/- 4 to 35 +/- 5 mEq (P < 0.01) and completely prevented the increase in mean arterial pressure in response to high salt in Group II. 5. The results suggest that Group II rabbits retain salt and fluid in response to their diet because of an abnormality in their control of renal nerve activity, possibly via vagal afferents. This results in blood pressure elevation because of an inability to lower peripheral resistance and heart rate in response to the increase in cardiac output. 6. Since they display several of the characteristics of salt-sensitive hypertensive humans, i.e. salt retention, normal plasma renin activity, but abnormal regulation of plasma renin activity and blood flow in response to salt loading, Group II are an appropriate model of human salt-induced hypertension.


Prevalence and clinical outcomes of triglyceride deposit cardiomyovasculopathy among haemodialysis patients.
To evaluate the effect of triglyceride deposit cardiomyovasculopathy (TGCV) on the cardiovascular outcomes in haemodialysis (HD) patients with suspected coronary artery disease (CAD). This retrospective single-centre observational study included data from the cardiac catheter database of Narita Memorial Hospital between April 2011 and March 2017. Among 654 consecutive patients on HD, the data for 83 patients with suspected CAD who underwent both [123I]-β-methyl-iodophenyl-pentadecanoic acid scintigraphy and coronary angiography were analysed. Patients were divided into three groups: definite TGCV (17 patients), probable TGCV (22 patients) and non-TGCV control group (44 patients). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke assessed for up to 5 years of follow-up. The prevalence of definite TGCV was approximately 20% and 2.6% among consecutive HD patients with suspected CAD and among all HD patients, respectively. At the end of the median follow-up period of 4.7 years, the primary endpoint was achieved in 52.9% of the definite TGCV patients (HR, 7.45; 95% CI: 2.28 to 24.3; p<0.001) and 27.3% of the probable TGCV patients (HR, 3.28; 95% CI: 0.93 to 11.6; p=0.066), compared with that in 9.1% of the non-TGCV control patients. Definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes among HD patients in all multivariate models. TGCV is not uncommon in HD patients and is associated with an increased risk of cardiovascular events including cardiovascular death. Thus, TGCV might be a potential therapeutic target.


Mapping of transgenic alleles in soybean using a nanopore-based sequencing strategy.
Transgenic technology was developed to introduce transgenes into various organisms to validate gene function and add genetic variations >40 years ago. However, the identification of the transgene insertion position is still challenging in organisms with complex genomes. Here, we report a nanopore-based method to map the insertion position of a Ds transposable element originating in maize in the soybean genome. In this method, an oligo probe is used to capture the DNA fragments containing the Ds element from pooled DNA samples of transgenic soybean plants. The Ds element-enriched DNAs are then sequenced using the MinION-based platform of Nanopore. This method allowed us to rapidly map the Ds insertion positions in 51 transgenic soybean lines through a single sequencing run. This strategy is high throughput, convenient, reliable, and cost-efficient. The transgenic allele mapping protocol can be easily translated to other eukaryotes with complex genomes.


Enabling Housing Cooperatives: policy lessons from Sweden, India and the United States.
Housing cooperatives became active in urban areas in Sweden, India and the United States during the interwar period. Yet, after the second world war, while housing cooperatives grew phenomenally nationwide in Sweden and India, they did not do so in the United States. This article makes a comparative institutional analysis of the evolution of housing cooperatives in these three countries. The analysis reveals that housing cooperatives' relationship with the state and the consequent support structures explain the divergent evolution. Although the relationships between cooperatives and the state evolved over time, they can be characterized as embedded autonomy, overembeddedness and disembeddedness in Sweden, India and the United States respectively. Whereas the consequent support structures for housing cooperatives became well developed in Sweden and India, such structures have been weak in the United States. The article highlights the need for embedded autonomy and the need for supportive structures to enable the growth of housing cooperatives.


Calspermin gene transcription is regulated by two cyclic AMP response elements contained in an alternative promoter in the calmodulin kinase IV gene.
The transcript for the high-affinity Ca2+/calmodulin-binding protein calspermin is generated from the gene encoding Ca2+/calmodulin-dependent protein kinase IV only in postmeiotic germ cells during spermatogenesis. We demonstrate that this testis-specific calspermin transcript can be produced in heterologous cells by utilization of a promoter located in an intron of the calmodulin (CaM) kinase IV gene. Critical motifs within this promoter are two cyclic AMP response element (CRE)-like sequences located about -70 and -50 bp upstream of the transcriptional initiation site. Both CRE motifs are footprinted by the authentic testis-specific transcriptional activator CREM tau or by CREM tau present in adult testis nuclear extract. Whereas a 2.1-kb DNA fragment containing the calspermin promoter is inactive when transfected into NIH 3T3 cells, activity can be restored by cotransfection of CREM tau and protein kinase A or CaM kinase IV but not CaM kinase II alpha. Restoration of activity is greatly reduced by mutation of the two CRE motifs. Since CRE-like motifs have been identified in many genes uniquely expressed in postmeiotic germ cells, which contain abundant CREM tau protein, we suggest that CREM tau may function as one transcription factor responsible for the expression of postmeiotic germ cell-specific genes.


Evidence for intact local connectivity but disrupted regional function in the occipital lobe in children and adolescents with schizophrenia.
It has long been known that specific visual frequencies result in greater blood flow to the striate cortex. These peaks are thought to reflect synchrony of local neuronal firing that is reflective of local cortical networks. Since disrupted neural connectivity is a possible etiology for schizophrenia, our goal was to investigate whether localized connectivity, as measured by aberrant synchrony, is abnormal in children and adolescents with schizophrenia. Subjects included 25 children and adolescents with schizophrenia and 39 controls matched for age and gender. Subjects were scanned on a Siemens 3 Tesla Trio scanner while observing flashing checkerboard presented at either 1, 4, 8, or 12 Hz. Image processing included both a standard GLM model and a Fourier transform analysis. Patients had significantly smaller volume of activation in the occipital lobe compared to controls. There were no differences in the integral or percent signal change of the hemodynamic response function for each of the four frequencies. Occipital activation was stable during development between childhood and late adolescence. Finally, both patients and controls demonstrated an increased response between 4 and 8 Hz consistent with synchrony or entrainment in the neuronal response. Children and adolescents with schizophrenia had a significantly lower volume of activation in the occipital lobe in response to the flashing checkerboard task. However, features of intact local connectivity in patients, such as the hemodynamic response function and maximal response at 8 Hz, were normal. These results are consistent with abnormalities in regional connectivity with preserved local connectivity in early-onset schizophrenia.


Developmental venous anomaly as a rare cause of obstructive hydrocephalus.
Developmental venous anomalies (DVA), previously known as cerebral venous malformations or venous angiomas, are common benign entities often incidentally discovered at MRI examinations. They are non‑pathologic variants of normal deep parenchymal veins that are usually asymptomatic, but they can rarely cause some complications. In this paper we described a rare case of obstructive hydrocephalus caused by a DVA located within the cerebral aqueduct and we also reviewed the previous literature on this topic. A 37‑year‑old man was diagnosed with symptomatic tri‑ventricular hydrocephalus that during the last year caused episodes of ictal headaches accompanied by vertigo, diaphoresis and lipothimic events. The MRI and the angiography showed the presence of a large collector vein coursing within the aqueduct, which was part of a complex DVA in the posterior fossa, responsible for the aqueductal stenosis and obstructive hydrocephalus. The patient was submitted to endoscopic third ventriculostomy (ETV) and then he had a complete resolution of symptoms. A literature review was performed through Medline Pubmed on papers published in English from 1937 to 2015 with the following key words: DVA, obstructive hydrocephalus, acqueductal stenosis, venous angioma, venous malformation, medullary malformation. Including our case, the literature research identified 16 reports in the Medline database for 18 patients presenting with obstructive hydrocephalus caused by a DVA including our case. In approximately 60% (10/17) of cases, the stenosis causing obstructive hydrocephalus was present in the cerebral aqueduct. The floor of the IV ventricle and the third ventricle were the second most common locations and DVAs were identified in 20% of cases (3/17) for each of these regions. In the remaining case the venous malformation was found in the Foramen of Monro. Clinical presentation before diagnosis lasted on average 23 months ranging from 1 month to 7 years. The mean age at diagnosis was 27 (range 3 days- 58 years). The most common presenting symptom was persistent headache, representing a major complaint in 80% of cases (12/15). In 78% (14/18) of cases MRI was crucial in the diagnosis. ETV was performed in 47% (8/17) of patients, whereas no treatment or clinical follow‑up was required in 18% (3/17) and VP Shunt in 12% (2/17) of cases. Instead, VA shunt, transcallosal approach and acqueductal stenting were performed in one patient each, corresponding singularly to 6% (1/17) of all cases. Despite the fact that DVAs are asymptomatic, they may rarely cause obstructive hydrocephalus because of impairment in the CSF flow. They should be considered in the differential diagnosis of any patient presenting with obstructive hydrocephalus. ETV has been demonstrated as an effective treatment option in the management of obstructive hydrocephalus due to a DVA.


American dental hygienists' attitudes towards chairside medical screening in a dental setting.
Targeted screening for medical conditions in a dental setting can be an effective strategy for early identification of individuals at increased disease risk. Dentists, patients and physicians have a favourable attitude towards this strategy. Given that dental hygienists (DHs) are involved in preventive and educational activities, this seems like a natural extension to their roles. We report on the attitudes of American DHs towards chairside medical screening. A 5-point Likert scale (1 = very important/willing, 5 = very unimportant/unwilling) survey was mailed to a nationwide random sample of US practicing DHs. Descriptive statistics were used for all questions, and the Friedman nonparametric analysis of variance was used for multi-element questions. A total of 3133 respondents returned the completed questionnaires for an effective response rate of 49.2% and a margin of error 1.8%. The majority of respondents felt it was important to perform/conduct chairside screening for hypertension (94%), diabetes mellitus (89%), cardiovascular disease (85%), HIV (79%) and hepatitis infection (78%); were willing to refer a patient for medical consult (94%), conduct screening that yields immediate results (85%); and were willing to collect the data/samples needed (57-95%). The most important considerations were dentist/owner support (98%), training (97%), patient willingness (98%) and time (98%). Similar to dentists, physicians and patients, the majority of the DHs had a favourable attitude towards chairside medical screening. Integrating the DH into screening activities is likely to require additional training and education regarding the diseases of interest, something that could be accomplished through continuing education courses and eventually incorporation into the educational curriculum.


Molecular requirements for bi-directional movement of phagosomes along microtubules.
Microtubules facilitate the maturation of phagosomes by favoring their interactions with endocytic compartments. Here, we show that phagosomes move within cells along tracks of several microns centrifugally and centripetally in a pH- and microtubule-dependent manner. Phagosome movement was reconstituted in vitro and required energy, cytosol and membrane proteins of this organelle. The activity or presence of these phagosome proteins was regulated as the organelle matured, with "late" phagosomes moving threefold more frequently than "early" ones. The majority of moving phagosomes were minus-end directed; the remainder moved towards microtubule plus-ends and a small subset moved bi-directionally. Minus-end movement showed pharmacological characteristics expected for dyneins, was inhibited by immunodepletion of cytoplasmic dynein and could be restored by addition of cytoplasmic dynein. Plus-end movement displayed pharmacological properties of kinesin, was inhibited partially by immunodepletion of kinesin and fully by addition of an anti-kinesin IgG. Immunodepletion of dynactin, a dynein-activating complex, inhibited only minus-end directed motility. Evidence is provided for a dynactin-associated kinase required for dynein-mediated vesicle transport. Movement in both directions was inhibited by peptide fragments from kinectin (a putative kinesin membrane receptor), derived from the region to which a motility-blocking antibody binds. Polypeptide subunits from these microtubule-based motility factors were detected on phagosomes by immunoblotting or immunoelectron microscopy. This is the first study using a single in vitro system that describes the roles played by kinesin, kinectin, cytoplasmic dynein, and dynactin in the microtubule-mediated movement of a purified membrane organelle.