Volitional action as perceptual detection: predictors of conscious intention in adolescents with tic disorders.
Voluntary actions are accompanied by a distinctive subjective experience, so that they feel quite different from physically similar involuntary movements. However, the nature and origin of this experience of volition remain unclear. Voluntary actions emerge during early childhood, in parallel with reduction of involuntary movements. However, the available markers of the experience of volition, notably Libet's mental chronometry of intention, cannot readily be used in young children. In Gilles de la Tourette syndrome (GTS), however, involuntary tic movements may coexist with voluntary control into adulthood. Therefore, adolescents with GTS could potentially confuse the two classes of movement. We have measured the temporal experience of voluntary action in a well-characterised group of adolescents with GTS, and age-matched controls. We replicated previous reports of a conscious intention occurring a few hundred milliseconds prior to voluntary keypress actions. Multiple regression across 25 patients' results showed that age and trait tic severity did not influence the experience of conscious intention. However, patients with stronger premonitory urges prior to tics showed significantly later conscious intentions, suggesting that the anticipatory experience of one's own volition involves a perceptual discrimination between potentially competing pre-movement signals. Patients who were more able to voluntarily suppress their tics showed significantly earlier conscious intention, suggesting that the perceptual discrimination between different action classes may also contribute to voluntary control of tics. We suggest that the brain learns voluntary control by perceptually discriminating a special class of internal 'intentional' signals, allowing them to emerge from motor noise.


Neutrophils from vasculitis patients exhibit an increased propensity for activation by anti-neutrophil cytoplasmic antibodies.
Anti-neutrophil cytoplasmic antibodies (ANCA) are thought to be pathogenic in ANCA-associated vasculitis (AAV) by stimulating polymorphonuclear leucocytes (PMNs) to degranulate and produce reactive oxygen species (ROS). The aim of this study was to investigate if PMNs from AAV patients are stimulated more readily by ANCA compared with PMNs from healthy controls (HCs). Differences in ANCA characteristics that can account for different stimulation potential were also studied. PMNs from five AAV patients and five HCs were stimulated with 10 different immunoglobulins (Ig)Gs, purified from PR3-ANCA-positive patients, and ROS production, degranulation and neutrophil extracellular trap (NET) formation was measured. ANCA levels, affinity and clinical data of the AAV donors were recorded. The results show that PMNs from AAV patients produce more intracellular ROS (P = 0·019), but degranulate to a similar extent as PMNs from HCs. ROS production correlated with NET formation. Factors that may influence the ability of ANCA to activate PMNs include affinity and specificity for N-terminal epitopes. In conclusion, our results indicate that PMNs from AAV patients in remission behave quite similarly to HC PMNs, with the exception of a greater intracellular ROS production. This could contribute to more extensive NET formation and thus an increased exposure of the ANCA autoantigens to the immune system.


Disease Modeling with Human Neurons Reveals LMNB1 Dysregulation Underlying DYT1 Dystonia.
DYT1 dystonia is a hereditary neurologic movement disorder characterized by uncontrollable muscle contractions. It is caused by a heterozygous mutation in Torsin A (TOR1A), a gene encoding a membrane-embedded ATPase. While animal models provide insights into disease mechanisms, significant species-dependent differences exist since animals with the identical heterozygous mutation fail to show pathology. Here, we model DYT1 by using human patient-specific cholinergic motor neurons (MNs) that are generated through either direct conversion of patients' skin fibroblasts or differentiation of induced pluripotent stem cells (iPSCs). These human MNs with the heterozygous TOR1A mutation show reduced neurite length and branches, markedly thickened nuclear lamina, disrupted nuclear morphology, and impaired nucleocytoplasmic transport (NCT) of mRNAs and proteins, whereas they lack the perinuclear "blebs" that are often observed in animal models. Furthermore, we uncover that the nuclear lamina protein LMNB1 is upregulated in DYT1 cells and exhibits abnormal subcellular distribution in a cholinergic MNs-specific manner. Such dysregulation of LMNB1 can be recapitulated by either ectopic expression of the mutant TOR1A gene or shRNA-mediated downregulation of endogenous TOR1A in healthy control MNs. Interestingly, downregulation of LMNB1 can largely ameliorate all the cellular defects in DYT1 MNs. These results reveal the value of disease modeling with human patient-specific neurons and indicate that dysregulation of LMNB1, a crucial component of the nuclear lamina, may constitute a major molecular mechanism underlying DYT1 pathology.SIGNIFICANCE STATEMENT Inaccessibility to patient neurons greatly impedes our understanding of the pathologic mechanisms for dystonia. In this study, we employ reprogrammed human patient-specific motor neurons (MNs) to model DYT1, the most severe hereditary form of dystonia. Our results reveal disease-dependent deficits in nuclear morphology and nucleocytoplasmic transport (NCT). Most importantly, we further identify LMNB1 dysregulation as a major contributor to these deficits, uncovering a new pathologic mechanism for DYT1 dystonia.


Genomic Mining of Phylogenetically Informative Nuclear Markers in Bark and Ambrosia Beetles.
Deep level insect relationships are generally difficult to resolve, especially within taxa of the most diverse and species rich holometabolous orders. In beetles, the major diversity occurs in the Phytophaga, including charismatic groups such as leaf beetles, longhorn beetles and weevils. Bark and ambrosia beetles are wood boring weevils that contribute 12 percent of the diversity encountered in Curculionidae, one of the largest families of beetles with more than 50000 described species. Phylogenetic resolution in groups of Cretaceous age has proven particularly difficult and requires large quantity of data. In this study, we investigated 100 nuclear genes in order to select a number of markers with low evolutionary rates and high phylogenetic signal. A PCR screening using degenerate primers was applied to 26 different weevil species. We obtained sequences from 57 of the 100 targeted genes. Sequences from each nuclear marker were aligned and examined for detecting multiple copies, pseudogenes and introns. Phylogenetic informativeness (PI) and the capacity for reconstruction of previously established phylogenetic relationships were used as proxies for selecting a subset of the 57 amplified genes. Finally, we selected 16 markers suitable for large-scale phylogenetics of Scolytinae and related weevil taxa.


Exploring the nature of situational goal-based coping in early-stage breast cancer patients: A contextual approach.
The psychosocial impact of breast cancer varies widely across patients and over time. Greater insight into goal-based coping processes theorised to underpin psychological resilience may inform efforts to support the maintenance and recovery of psychological wellbeing in the context of breast cancer treatment and recovery. This prospective study adopted a qualitative descriptive design to better understand the nature of situational goal-based coping in response to personal goal interference encountered across the six months following surgery for early-stage breast cancer. Responses to specific instances of goal interference were derived from semi-structured interviews conducted at three time-points following surgery (i.e., approximately two, four, and six months post-surgery). Thematic and cross-case analytic techniques were utilised to identify broad patterns across the goal-specific response trajectories. Three broad response patterns were identified - goal-based coping only, combined goal-based coping and other (i.e., informed waiting and/or passive) responses, and informed waiting and/or passive responses only. Specific response patterns were further identified within each category. The majority of response trajectories incorporated the utilisation of assimilative and/or accommodative goal-based coping. Early-stage breast cancer patients utilised goal-based coping in response to many instances of goal-specific interference encountered during the study period. While the initial or delayed activation of these processes appeared generally adaptive, there was also evidence of maladaptive coping and blocked goal pursuit. Further insight into the nature of adaptive and maladaptive goal-based coping in this context could help oncology nurses facilitate ongoing personal goal pursuit and psychological resilience across the cancer continuum.


Inhibition of Human Neutrophil Responses by the Essential Oil of Artemisia kotuchovii and Its Constituents.
Essential oils were obtained by hydrodistillation of the flowers+leaves and stems of Artemisia kotuchovii Kupr. (AKEO(f+l) and AKEO(stm), respectively) and analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). The primary components of the oils were estragole, (E)- and (Z)-β-ocimenes, methyleugenol, limonene, spathulenol, β-pinene, myrcene, and (E)-methyl cinnamate. Seventy-four constituents were present at concentrations from 0.1 to 1.0%, and 34 compounds were identified in trace (<0.1%) amounts in one or both plant components. Screening of the essential oils for biological activity showed that AKEO(stm), but not AKEOf+l, inhibited N-formyl-Met-Leu-Phe (fMLF)-stimulated Ca(2+) flux and chemotaxis and phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production in human neutrophils. Selected pure constituents, representing >96% of the AKEO(stm) composition, were also tested in human neutrophils and HL-60 cells transfected with N-formyl peptide receptor 1 (FPR1). One component, 6-methyl-3,5-heptadien-2-one (MHDO), inhibited fMLF- and interleukin 8 (IL-8)-stimulated Ca(2+) flux, fMLF-induced chemotaxis, and PMA-induced ROS production in human neutrophils. MHDO also inhibited fMLF-induced Ca(2+) flux in FPR1-HL60 cells. These results suggest that MHDO may be effective in modulating some innate immune responses, possibly by inhibition of neutrophil migration and ROS production.


Abundance, distribution and potential activity of methane oxidizing bacteria in permafrost soils from the Lena Delta, Siberia.
The methane oxidation potential of active layer profiles of permafrost soils from the Lena Delta, Siberia, was studied with regard to its respond to temperature, and abundance and distribution of type I and type II methanotrophs. Our results indicate vertical shifts within the optimal methane oxidation temperature and within the distribution of type I and type II methanotrophs. In the upper active layer, maximum methane oxidation potentials were detected at 21 degrees C. Deep active layer zones that are constantly exposed to temperatures below 2 degrees C showed a maximum potential to oxidize methane at 4 degrees C. Our results indicate a dominance of psychrophilic methanotrophs close to the permafrost table. Type I methanotrophs dominated throughout the active layer profiles but their number strongly fluctuated with depth. In contrast, type II methanotrophs were constantly abundant through the whole active layer and displaced type I methanotrophs close to the permafrost table. No correlation between in situ temperatures and the distribution of type I and type II methanotrophs was found. However, the distribution of type I and type II methanotrophs correlated significantly with in situ methane concentrations. Beside vertical fluctuations, the abundance of methane oxidizers also fluctuated according to different geomorphic units. Similar methanotroph cell counts were detected in samples of a flood plain and a polygon rim, whereas cell counts in samples of a polygon centre were up to 100 times lower.


The systemic pathology of Venezuelan equine encephalitis virus infection in humans.
The histopathology of fatal Venezuelan equine encephalitis (VEE) in humans has not been well documented. To evaluate the spectrum of disease in man, the histologic slides of the 21 autopsied patients who died with documented VEE infection during the 1962-63 VEE epidemic in Zulia, Venezuela were reviewed. The main histopathologic lesion observed in multiple organs and tissues, especially the brain, gastrointestinal tract, and lungs, was moderate to marked diffuse congestion and edema with hemorrhage. In the central nervous system (CNS), mild or focal mixed inflammatory cell infiltrates were present in the leptomeninges and perivascular spaces (65%). Meningoencephalitis associated with intense necrotizing vasculitis was observed in 2 patients (10%), and cerebritis was observed in 5 cases (25%). There was a striking depletion of lymphocytes with vascular thrombosis and necrosis of follicles in lymph nodes (77%), spleen (69%), and the gastrointestinal tract (90%). Widespread hepatocellular degeneration and individual cell necrosis was observed in 61% of the cases. Most patients (90%) had interstitial pneumonia, frequently complicated by acute bronchopneumonia (33%). Overall, the lesions observed in the CNS and reticuloendothelial tissues are comparable to what is observed in experimental animals; however, extensive hepatocellular degeneration and interstitial pneumonia are not prominent pathologic features of VEE in animals. The findings are consistent with the hypothesis that lymphoid and reticuloendothelial tissues are the targets in VEE virus infection in humans, and that many of the histopathologic changes are attributable to primary lymphoid and endothelial cell injury.


First Report of Alfalfa mosaic virus Infecting Basil (Ocimum basilicum) in California.
Basil (Ocimum basilicum L.) plants collected from three fields in Imperial County, CA in May, 2011 were found to be exhibiting yellowing, chlorotic sectors and spots on leaves, resulting in unmarketable plants. Dodder (Cuscuta spp.) was present in one of the fields, but was not visibly associated with symptomatic plants. Total nucleic acid was extracted from four symptomatic and three asymptomatic basil plants, as well as from the dodder plant with the RNeasy Plant Mini Kit (Qiagen, Valencia, CA). Nucleic acid extracts were tested by reverse transcription (RT)-PCR for the presence of Alfalfa mosaic virus (AMV) using primers designed to amplify a 350-nt region of the AMV coat protein gene (3). RT-PCR produced bands of the expected size in extracts from all symptomatic plants and the dodder sample. No amplification was obtained from symptomless plants. A 350-nt band amplified from one plant was gel-extracted, sequenced (TACGen, Richmond, CA), and confirmed to be AMV by comparison to sequences available in GenBank (Accession No. K02703). Although serological tests on an initial basil sample were negative for AMV by ELISA using antiserum produced against AMV by R. Larsen, USDA-ARS, Prosser, WA (unpublished), AMV was confirmed by ELISA and RT-PCR in symptomatic Nicotiana benthamiana, N. clevelandii, and Malva parviflora plants following mechanical transmission from basil source plants. The fields with AMV infections were located at opposite ends of the production region from one another, indicating widespread dispersal of AMV in the region. All AMV positive plants were adjacent to alfalfa. Two additional basil plantings in shade houses open to the outside environment did not have AMV symptomatic plants and were also confirmed negative by RT-PCR, but these plantings were at the extreme north end of Imperial Valley agriculture and well away from any alfalfa fields. At the time the basil plantations were sampled for AMV, no aphids were found in any plantations, but during the several weeks prior to finding the AMV-positive plants, cowpea aphid, Aphis craccivora Koch; pea aphid, Acyrthosiphon pisum Harris; blue alfalfa aphid, Acyrthosiphon kondoi Shinji; and spotted alfalfa aphid, Therioaphis maculata Buckton were colonizing Imperial Valley alfalfa fields, producing winged adults. AMV is transmitted by at least 14 aphid species (1), and most aphid populations increase during the late spring in this important desert agricultural region. The acquisition of AMV by dodder suggests the parasitic plant may serve as a vector of AMV within basil fields, although further study will be necessary for clarification. Significant acreage of basil is grown in the Imperial Valley. This acreage is surrounded by extensive and increasing alfalfa production totaling 55,442 ha (137,000 acres) in Imperial County and representing a 21% increase in acreage over 2009 for the same region (2). To our knowledge, this is the first report of basil infected by AMV in California. The proximity of basil production to such a large alfalfa production region warrants the need for enhanced efforts at aphid management in basil production to reduce vector populations and reduce transmission to basil crops. References: (1) E. M. Jaspars and L. Bos. Alfalfa mosaic virus. No. 229 in: Descriptions of Plant Viruses. Commonw. Mycol. Inst./Assoc. Appl. Biol., Kew, England, 1980. (2) C. Valenzuela. Imperial County California Crop and Livestock Report, 2010. (3) H. Xu and J. Nie. Phytopathology 96:1237, 2006.


Inactivation of p53 increases the cytotoxicity of camptothecin in human colon HCT116 and breast MCF-7 cancer cells.
Camptothecin (CPT) derivatives are topoisomerase I (top1) inhibitors recently introduced as clinical agents. To explore the role of p53 in CPT-induced cytotoxicity, we examined CPT effects in two isogenic pairs of human cancer cell lines, MCF-7 breast carcinoma and HCT116 colon carcinoma cells, in which p53 function had been disrupted by transfection with the human papillomavirus type-16 E6 gene. Clonogenic survival assays showed that both MCF-7/E6 and HCT116/E6 cells were more sensitive to CPT. No differences in top1 protein levels and activity analyzed by a novel in vitro oligonucleotide assay were observed in the E6 transfectants. Also, CPT showed comparable top1 cleavable complex formation in vivo, as determined by DNA single-strand breaks and DNA protein cross-links. These results suggest that p53 can protect against CPT-induced cytotoxicity and that this protection is mediated downstream of CPT-induced DNA damage. Flow cytometry analyses showed that CPT can induce G1 arrest in cells with normal p53. This G1 arrest was markedly reduced in the p53-deficient cells. These results demonstrate a critical role of p53 as a G1 checkpoint regulator after CPT-induced DNA damage and suggest a rationale for the selectivity of CPT toward tumors with p53 mutations.


Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species.
Regulated production of reactive oxygen species (ROS)/reactive nitrogen species (RNS) adequately balanced by antioxidant systems is a prerequisite for the participation of these active substances in physiological processes, including insulin action. Yet, increasing evidence implicates ROS and RNS as negative regulators of insulin signaling, rendering them putative mediators in the development of insulin resistance, a common endocrine abnormality that accompanies obesity and is a risk factor of type 2 diabetes. This review deals with this dual, seemingly contradictory, function of ROS and RNS in regulating insulin action: the major processes for ROS and RNS generation and detoxification are presented, and a critical review of the evidence that they participate in the positive and negative regulation of insulin action is provided. The cellular and molecular mechanisms by which ROS and RNS are thought to participate in normal insulin action and in the induction of insulin resistance are then described. Finally, we explore the potential usefulness and the challenges in modulating the oxidant-antioxidant balance as a potentially promising, but currently disappointing, means of improving insulin action in insulin resistance-associated conditions, leading causes of human morbidity and mortality of our era.


Intralobar pulmonary sequestration with congenital cystic adematous malformation and rhabdomyomatous dysplasia.
Pulmonary sequestration and congenital cystic adenomatous malformations (CCAM) are well known but still uncommon anomalies of the lung. Extralobar sequestrations are well described in association with CCAM, but fewer intralobar lesions are found with this association. The existence of striated muscle within CCAM is described, and we have evidence of dysplastic changes within the various cellular components occurring, with rhabdomyomatous dysplasia being one of these. A literature review shows no previous evidence of a reported intralobar sequestration associated with CCAM and rhabdomyomatous dysplastic changes.


Incidence of cutaneous malignant melanoma by socioeconomic status in Canada: 1992-2006.
There are no nationwide studies documenting changes in cutaneous malignant melanoma incidence or association of incidence with socioeconomic status (SES) in Canada. We sought to determine whether melanoma incidence increased from 1992 to 2006 and if there was an association between SES and melanoma incidence. Additionally, we studied whether there was a correlation between province of residence and melanoma incidence. Cases from the Canadian Cancer Registry were reviewed. Demographic and socioeconomic information were extracted from the Canadian Census of Population data. Cases were linked to income quintiles by postal code. A negative binomial regression was performed to identify relationships among these variables. Overall incidence of melanoma in Canada increased by 67 % from 1992 to 2006 (p < 0.0001). The increase in incidence was greater for melanoma in situ compared with invasive melanoma (136 % versus 52 % [p < 0.0001]). Incidence was positively correlated with higher income quintiles; the incidence rates among patients in the lowest income quintiles were 67 % of that for the highest income quintiles (p < 0.0001). A wide variety of explanations have been postulated for an increased incidence in melanoma among persons of higher SES, including access to and awareness of screening, more access to vacations in sunny climates, and increased leisure time. Variations in incidence of melanoma by urban vs. rural location and province may indicate differences in access to dermatologists across Canada. Melanoma incidence is increasing in Canada and is higher among people in high SES groups. This rise is likely due to a combination of factors including a true rise in incidence due to increases in sun exposure, and also an increased detection rate, particularly in those who are more aware of the disease and have access to resources for detection.


Licensure portability: assuring access to quality care in physical therapy.
The concurrent circumstances of an increasingly mobile workforce, disparities in access to healthcare, and the ability to deliver care through technology (e.g., telehealth) present the need and the opportunity for practice across state borders. Over the past four years, the Federation of State Boards of Physical Therapy (FSBPT) has explored professional licensure models that will allow cross border practice. This paper reviews FSBPT's exploratory process and describes some of the advantages of an interstate compact. It concludes that if agreement among state licensing boards can be achieved, a compact could serve as a viable means to increase patient access to quality physical therapy care.


Novel roles for ATP-binding cassette G transporters in lipid redistribution in Toxoplasma.
Toxoplasma is a protozoan parasite proficiently adapted to thrive in a parasitophorous vacuole (PV) formed in the cytoplasm of a large variety of mammalian cells. As an actively dividing organism, the parasite must adjust the lipid composition of its membranes to preserve organelle vitality and expand the size of the PV membrane to accommodate growing progeny. We showed that Toxoplasma takes up host lipids and can expel major lipids in an ATP-dependent process. In order to provide detailed mechanistic insights into lipid trafficking phenomena relevant to Toxoplasma biology, we characterized six parasite ATP-binding cassette (ABC) G family transporters and investigated their potential contribution to lipid homeostatic processes. All these transporters are expressed in the parasite and five of them are upregulated upon exposure to sterols. Four ABCG are localized to secretory organelles and the plasma membrane, and promote cholesterol and phospholipid efflux, reflecting the importance in exportation of large amounts of lipids into the PV. Interestingly, one ABCG that is associated with vesicles in the PV and the plasma membrane acts as a cholesterol importer. This last finding expands our current view on the role of some ABCG transporters in eukaryotic sterol influx.


Molecular insight on the binding of NNRTI to K103N mutated HIV-1 RT: molecular dynamics simulations and dynamic pharmacophore analysis.
Regardless of advances in anti-HIV therapy, HIV infection remains an immense challenge due to the rapid onset of mutation instigating drug resistance. Rilpivirine is a second generation di-aryl pyrimidine (DAPY) derivative, known to effectively inhibit wild-type (WT) as well as various mutant HIV-1 reverse transcriptase (RT). In this study, a cumulative 240 ns of molecular dynamic (MD) simulations of WT HIV-1 RT and its corresponding K103N mutated form, complexed with rilpivirine, were performed in solution. Conformational analysis of the NNRTI inside the binding pocket (NNIBP) revealed the ability of rilpivirine to adopt different conformations, which is possibly the reason for its reasonable activity against mutant HIV-1 RT. Binding free energy (MM-PB/GB SA) calculations of rilpivirine with mutant HIV-1 RT are in agreement with experimental data. The dynamics of interaction patterns were investigated based on the MD simulations using dynophores, a novel approach for MD-based ligand-target interaction mapping. The results from this interaction profile analysis suggest an alternate interaction between the linker N atom of rilpivirine and Lys 101, potentially providing the stability for ligand binding. PCA analysis and per residue fluctuation has highlighted the significant role of flexible thumb and finger sub-domains of RT in its biological activity. This study investigated the underlying reason for rilpivirine's improved inhibitory profile against mutant RT, which could be helpful to understand the molecular basis of HIV-1 RT drug resistance and design novel NNRTIs with improved drug resistance tolerance.


Effect of miR-146 targeted HDMCP up-regulation in the pathogenesis of nonalcoholic steatohepatitis.
Mitochondrial dysfunction plays an important role inthe pathogenesis of nonalcoholic steatohepatitis (NASH), where uncoupling protein (UCP) is actively involved. We previously reported the uncoupling activity of HDMCP and its role in liver steatosis. We now aim to investigate the degree and therapeutic effect of HDMCP in NASH and the regulatory role of miR-146 on HDMCP. NASH animal model was established by feeding BALB/c mice with MCD diet while L02 cell was cultured with high concentration of fatty acid (HFFA) for 72h to mimic the steatosis and inflammation of NASH in-vitro appearance. The steatosis level was assessed by H-E/oil-red staining and serum/supernatant marker detection. The inflammation activity was evaluated by levels of Hepatic activity index, transwell, apoptosis degree (TUNEL/flow cytometry) and serum/supernatant marker. HDMCP level was detected by western blot and miRNA expression was tested by qRT-PCR. NASH severity change was recorded after RNA interference while the regulatory role of miR-146 on HDMCP was confirmed by dual luciferase report system. The H2O2 and ATP levels were measured for mechanism exploration. Increased HDMCP expression was identified in NASH animal model and HFFA-72h cultured L02 cell. Moreover, under regulation of miR-146, NASH alleviation was achieved after HDMCP downregulation in both in vivo and in vitro, according to the declination of steatosis and inflammation related markers. Though H2O2 and ATP levels were increased and decreased in NASH models, HDMCP down regulation both increased their levels. The miR-146-HDMCP-ATP/H2O2 pathway may provide novel mechanism and treatment option for NASH.


Audiovisual Integration Delayed by Stimulus Onset Asynchrony Between Auditory and Visual Stimuli in Older Adults.
Although neuronal studies have shown that audiovisual integration is regulated by temporal factors, there is still little knowledge about the impact of temporal factors on audiovisual integration in older adults. To clarify how stimulus onset asynchrony (SOA) between auditory and visual stimuli modulates age-related audiovisual integration, 20 younger adults (21-24 years) and 20 older adults (61-80 years) were instructed to perform an auditory or visual stimuli discrimination experiment. The results showed that in younger adults, audiovisual integration was altered from an enhancement (AV, A ± 50 V) to a depression (A ± 150 V). In older adults, the alterative pattern was similar to that for younger adults with the expansion of SOA; however, older adults showed significantly delayed onset for the time-window-of-integration and peak latency in all conditions, which further demonstrated that audiovisual integration was delayed more severely with the expansion of SOA, especially in the peak latency for V-preceded-A conditions in older adults. Our study suggested that audiovisual facilitative integration occurs only within a certain SOA range (e.g., -50 to 50 ms) in both younger and older adults. Moreover, our results confirm that the response for older adults was slowed and provided empirical evidence that integration ability is much more sensitive to the temporal alignment of audiovisual stimuli in older adults.


The Influence of Respondent Characteristics on the Validity of Self-Reported Survey Responses.
To examine concordance between member self-reports and the organization's administrative claims data for two key health factors: number of chronic conditions, and number of prescription drugs. Medicare Advantage plan claims data and member survey data from 2011 to 2012. Mailed surveys to 15,000 members, enrolled minimum 6 months, drawn from a random sample of primary care physician practices with at least 200 members. Descriptive statistics were generated for extent of concordance. Multivariable logistic regressions were used to analyze the association of selected respondent characteristics with likelihood of concordance. Concordance for number of chronic conditions was 58.4 percent, with 27.3 percent under-reporting, 14.2 percent over-reporting. Concordance for number of prescription drugs was 56.6 percent with 38.9 percent under-reporting, 4.5 percent over-reporting. Number of prescriptions and assistance in survey completion were associated with higher likelihood of concordance for chronic conditions. Assistance in survey completion and number of chronic conditions were associated with higher concordance, and age and number of prescriptions were associated with lower concordance, for prescription drugs. Self-reported number of chronic conditions and prescription medications are not in high concordance with claims data. Health care researchers and policy makers using patient self-reported data should be aware of these potential biases.


Tea drinking is associated with benefits on bone density in older women.
Impaired hip structure assessed by dual-energy X-ray absorptiometry (DXA) areal bone mineral density (aBMD) is an independent predictor for osteoporotic hip fracture. Some studies suggest that tea intake may protect against bone loss. Using both cross-sectional and longitudinal study designs, we examined the relation of tea consumption with hip structure. Randomly selected women (n = 1500) aged 70-85 y participated in a 5-y prospective trial to evaluate whether oral calcium supplements prevent osteoporotic fractures. aBMD at the hip was measured at years 1 and 5 with DXA. A cross-sectional analysis of 1027 of these women at 5 y assessed the relation of usual tea intake, measured by using a questionnaire, with aBMD. A prospective analysis of 164 women assessed the relation of tea intake at baseline, measured by using a 24-h dietary recall, with change in aBMD from years 1 to 5. In the cross-sectional analysis, total hip aBMD was 2.8% greater in tea drinkers (x: 806; 95% CI: 797, 815 mg/cm(2)) than in non-tea drinkers (784; 764, 803 mg/cm(2)) (P < 0.05). In the prospective analysis over 4 y, tea drinkers lost an average of 1.6% of their total hip aBMD (-32; -45, -19 mg/cm(2)), but non-tea drinkers lost 4.0% (-13; -20, -5 mg/cm(2)) (P < 0.05). Adjustment for covariates did not influence the interpretation of results. Tea drinking is associated with preservation of hip structure in elderly women. This finding provides further evidence of the beneficial effects of tea consumption on the skeleton.


Endovascular treatment of wide-necked aneurysms of the visceral and renal arteries using the double microcatheter technique via a single access route.
We aimed to evaluate the utility of and complications associated with the double microcatheter technique for the treatment of wide-necked visceral and renal artery aneurysms (VRAAs). Nine patients (mean age, 58 years; age range, 42-69 years; 4 men, 5 women) with wide-necked VRAAs who underwent treatment with the double microcatheter technique from January 2016 to July 2018 were included in the study. For all patients, anatomical features were confirmed using cone-beam computed tomography (CT) with rotational angiography. The aneurysmal location, size, volume, neck-to-dome ratio, number of coils used, and coil packing density were investigated. Technical success, complications (coil migration and organ ischemia), changes in the complete blood count or serum creatine level, and recurrence were also evaluated. Three renal artery aneurysms and 6 splenic artery aneurysms were treated by the double microcatheter technique. The mean size of the aneurysms was 26.09±4.76 mm, mean volume was 6.19±3.69 cm3, and mean neck-to-dome ratio was 1.53±0.24. The number of coils used ranged from 7 to 16. The mean packing density was 11.32%±3.72%. Technical success was achieved in all 9 patients. Renal ischemia occurred in two patients with renal artery aneurysm, one of whom showed minimal scar formation on follow-up CT after infarction. No coil migrations or disease recurrences were observed. The double microcatheter technique for the treatment of wide-necked VRAAs appears to be relatively safe and useful. However, complex renal artery aneurysm should be carefully managed in order to prevent infarction.


Epidemiological investigation for grouped cases of Trichosporon asahii using whole genome and IGS1 sequencing.
Trichosporonosis is a rare invasive infection in humans mainly due to Trichosporon asahii, and especially recovered from patients having haematological malignancy. Since 2012, IGS1 region sequencing is used as a genotyping method to distinguish isolates, with high frequency of one haplotype worldwide and a geographic specificity for some haplotypes. We compared the IGS1 genotyping method and whole genome sequencing (WGS) to study the relationship between clinical isolates involved in two grouped cases in France. IGS1 sequencing and antifungal susceptibility testing were performed for 54 clinical isolates. Clinical data for 28 isolates included in surveillance programs were analysed. Whole genome was sequenced for 32 clinical isolates and the type strain. All isolates were intrinsically resistant to flucytosine, while voriconazole had the most potent in vitro activity. The majority of the isolates was recovered from patients with haematological malignancies (42.86%), with a high proportion of children (<15 yrs-old, 32.14%) and a high mortality rate at three months (46.15%). Based on the WGS analysis, isolates exhibiting IGS1 haplotype 1, 3 and 7 belonged to different clades. Five isolates recovered during the first grouped cases had the same IGS1 haplotype and shared 99% of SNPs similarity. For the second grouped cases, four isolates had 98.7% of SNPs similarity while the isolate recovered 4 years earlier was totally unlinked. We confirmed the usefulness of IGS1 sequencing for grouped cases infection of T. asahii. We underlined its limitation for the study of population structure and the utility of WGS analysis for the study of epidemiologically unrelated isolates.


Dengue Knowledge and Preventive Practices in Iquitos, Peru.
As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had < 5-year-old children at home. Although dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved.


Position Effects Influence Transvection in Drosophila melanogaster.
Transvection is an epigenetic phenomenon wherein regulatory elements communicate between different chromosomes in trans, and is thereby dependent upon the three-dimensional organization of the genome. Transvection is best understood in Drosophila, where homologous chromosomes are closely paired in most somatic nuclei, although similar phenomena have been observed in other species. Previous data have supported that the Drosophila genome is generally permissive to enhancer action in trans, a form of transvection where an enhancer on one homolog activates gene expression from a promoter on a paired homolog. However, the capacity of different genomic positions to influence the quantitative output of transvection has yet to be addressed. To investigate this question, we employed a transgenic system that assesses and compares enhancer action in cis and in trans at defined chromosomal locations. Using the strong synthetic eye-specific enhancer GMR, we show that loci supporting strong cis-expression tend to support robust enhancer action in trans, whereas locations with weaker cis-expression show reduced transvection in a fluorescent reporter assay. Our subsequent analysis is consistent with a model wherein the chromatin state of the transgenic insertion site is a primary determinant of the degree to which enhancer action in trans will be supported, whereas other factors such as locus-specific variation in somatic homolog pairing are of less importance in influencing position effects on transvection.


Regional lung perfusion estimated by electrical impedance tomography in a piglet model of lung collapse.
The assessment of the regional match between alveolar ventilation and perfusion in critically ill patients requires simultaneous measurements of both parameters. Ideally, assessment of lung perfusion should be performed in real-time with an imaging technology that provides, through fast acquisition of sequential images, information about the regional dynamics or regional kinetics of an appropriate tracer. We present a novel electrical impedance tomography (EIT)-based method that quantitatively estimates regional lung perfusion based on first-pass kinetics of a bolus of hypertonic saline contrast. Pulmonary blood flow was measured in six piglets during control and unilateral or bilateral lung collapse conditions. The first-pass kinetics method showed good agreement with the estimates obtained by single-photon-emission computerized tomography (SPECT). The mean difference (SPECT minus EIT) between fractional blood flow to lung areas suffering atelectasis was -0.6%, with a SD of 2.9%. This method outperformed the estimates of lung perfusion based on impedance pulsatility. In conclusion, we describe a novel method based on EIT for estimating regional lung perfusion at the bedside. In both healthy and injured lung conditions, the distribution of pulmonary blood flow as assessed by EIT agreed well with the one obtained by SPECT. The method proposed in this study has the potential to contribute to a better understanding of the behavior of regional perfusion under different lung and therapeutic conditions.


The effects of donor age on organ transplants: A review and implications for aging research.
Despite the considerable amount of data available on the effect of donor age upon the outcomes of organ transplantation, these still represent an underutilized resource in aging research. In this review, we have compiled relevant studies that analyze the effect of donor age in graft and patient survival following liver, kidney, pancreas, heart, lung and cornea transplantation, with the aim of deriving insights into possible differential aging rates between the different organs. Overall, older donor age is associated with worse outcomes for all the organs studied. Nonetheless, the donor age from which the negative effects upon graft or patient survival starts to be significant varies between organs. In kidney transplantation, this age is within the third decade of life while the data for heart transplantation suggest a significant effect starting from donors over age 40. This threshold was less defined in liver transplantation where it ranges between 30 and 50 years. The results for the pancreas are also suggestive of a detrimental effect starting at a donor age of around 40, although these are mainly derived from simultaneous pancreas-kidney transplantation data. In lung transplantation, a clear effect was only seen for donors over 65, with negative effects of donor age upon transplantation outcomes likely beginning after age 50. Corneal transplants appear to be less affected by donor age as the majority of studies were unable to find any effect of donor age during the first few years posttransplantation. Overall, patterns of the effect of donor age in patient and graft survival were observed for several organ types and placed in the context of knowledge on aging.


Preparative separation and purification of four cis-trans isomers of coumaroylspermidine analogs from safflower by high-speed counter-current chromatography.
High-speed counter-current chromatography (HSCCC) was successfully applied for the first time to isolate and purify four cis-trans isomers of coumaroylspermidine analogs from Safflower. HSCCC separation was achieved with a two-phase solvent system composed of chloroform-methanol-water (1:1:1, v/v/v) with the upper phase as the mobile phase. In a single run, a total of 1.3mg of N(1), N(5), N(10)-(E)-tri-p-coumaroylspermidine (EEE), 4.4mg of N(1)(E)-N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine (EZE), 7.2mg of N(1)(Z)-N(5)-(Z)-N(10)-(E)-tri-p-coumaroylspermidine (ZZE), and 11.5mg of N(1),N(5),N(10)-(Z)-tri-p-coumaroylspermidine (ZZZ) were obtained from 100mg of crude sample. High Performance Liquid Chromatography (HPLC) analysis showed that the purities of these four components are 95.5%, 98.1%, 97.5% and 96.2%, respectively. The chemical structures were identified by ESI-MS, (1)H NMR and (13)C NMR.


Effect of fibroblast-seeded artificial dermis on wound healing.
In covering wounds, efforts should include use of the safest and least invasive methods with a goal of achieving optimal functional and cosmetic outcome. The recent development of advanced technology in wound healing has triggered the use of cells and/or biological dermis to improve wound healing conditions. The purpose of the study was to evaluate the effects of fibroblast-seeded artificial dermis on wound healing efficacy.Ten nude mice were used in this study. Four full-thickness 6-mm punch wounds were created on the dorsal surface of each mouse (total, 40 wounds). The wounds were randomly assigned to one of the following 4 treatments: topical application of Dulbecco phosphate-buffered saline (control), human fibroblasts (FB), artificial dermis (AD), and human fibroblast-seeded artificial dermis (AD with FB). On the 14th day after treatment, wound healing rate and wound contraction, which are the 2 main factors determining wound healing efficacy, were evaluated using a stereoimage optical topometer system, histomorphological analysis, and immunohistochemistry.The results of the stereoimage optical topometer system demonstrated that the FB group did not have significant influence on wound healing rate and wound contraction. The AD group showed reduced wound contraction, but wound healing was delayed. The AD with FB group showed decreased wound contraction without significantly delayed wound healing. Histomorphological analysis exhibited that more normal skin structure was regenerated in the AD with FB group. Immunohistochemistry demonstrated that the AD group and the AD with FB group produced less α-smooth muscle actin than the control group, but this was not shown in the FB group.Fibroblast-seeded artificial dermis may minimize wound contraction without significantly delaying wound healing in the treatment of skin and soft tissue defects.


Bacteriocin-mediated competition in cystic fibrosis lung infections.
Bacteriocins are toxins produced by bacteria to kill competitors of the same species. Theory and laboratory experiments suggest that bacteriocin production and immunity play a key role in the competitive dynamics of bacterial strains. The extent to which this is the case in natural populations,especially human pathogens, remains to be tested. We examined the role of bacteriocins in competition using Pseudomonas aeruginosa strains infecting lungs of humans with cystic fibrosis (CF). We assessed the ability of different strains to kill each other using phenotypic assays, and sequenced their genomes to determine what bacteriocins (pyocins) they carry. We found that(i) isolates from later infection stages inhibited earlier infecting strains less,but were more inhibited by pyocins produced by earlier infecting strains and carried fewer pyocin types; (ii) this difference between early and late infections appears to be caused by a difference in pyocin diversity between competing genotypes and not by loss of pyocin genes within a lineage overtime; (iii) pyocin inhibition does not explain why certain strains outcompete others within lung infections; (iv) strains frequently carry the pyocin-killing gene, but not the immunity gene, suggesting resistance occurs via other unknown mechanisms. Our results show that, in contrast to patterns observed in experimental studies, pyocin production does not appear to have a major influence on strain competition during CF lung infections.


Long-term outcomes of pediatric arteriovenous malformations: the 30-year Pittsburgh experience.
The study of pediatric arteriovenous malformations (pAVMs) is complicated by the rarity of the entity. Treatment choice has often been affected by the availability of different modalities and the experience of the providers present. The University of Pittsburgh experience of multimodality treatment of pAVMs is presented. The authors conducted a retrospective cohort study examining 212 patients with pAVM presenting to the University of Pittsburgh between 1988 and 2018, during which patients had access to surgical, endovascular, and radiosurgical options. Univariate analysis was performed comparing good and poor outcomes. A poor outcome was defined as a modified Rankin Scale (mRS) score of ≥ 3. Multivariate analysis via logistic regression was performed on appropriate variables with a p value of ≤ 0.2. Seventy-five percent of the cohort had at least 3 years of follow-up. Five patients (2.4%) did not receive any intervention, 131 (61.8%) had GKRS alone, 14 (6.6%) had craniotomies alone, and 2 (0.9%) had embolization alone. Twenty-two (10.4%) had embolization and Gamma Knife radiosurgery (GKRS); 20 (9.4%) had craniotomies and GKRS; 8 (3.8%) had embolization and craniotomies; and 10 (4.7%) had embolization, craniotomies, and GKRS. Thirty-one patients (14.6%) were found to have poor outcome on follow-up. The multivariate analysis performed in patients with poor outcomes was notable for associations with no treatment (OR 18.9, p = 0.02), hemorrhage requiring craniotomy for decompression alone (OR 6, p = 0.03), preoperative mRS score (OR 2.1, p = 0.004), and Spetzler-Martin score (OR 1.8, p = 0.0005). The mean follow-up was 79.7 ± 62.1 months. The confirmed radiographic obliteration rate was 79.4% and there were 5 recurrences found on average 9.5 years after treatment. High rates of long-term functional independence (mRS score of ≤ 2) can be achieved with comprehensive multimodality treatment of pAVMs. At this center there was no difference in outcome based on treatment choice when accounting for factors such as Spetzler-Martin grade and presenting morbidity. Recurrences are rare but frequently occur years after treatment, emphasizing the need for long-term screening after obliteration.


Geographic, clinical, serologic, and molecular evidence of granulocytic ehrlichiosis, a likely zoonotic disease, in Minnesota and Wisconsin dogs.
Seventeen Minnesota and Wisconsin dogs with granulocytic ehrlichosis were studied. The diagnoses were made by finding ehrlichia morulae in peripheral blood neutrophils. Eight dogs were studied retrospectively, and nine dogs were studied prospectively. The medical records of all dogs were reviewed. Eighty-eight percent of the dogs were purebred and 76% were spayed females. The median age was 8 years. Sixty-five percent of the cases were diagnosed in October and November. Fever and lethargy were the most common clinical signs. The most frequent laboratory findings were lymphopenia, thrombocytopenia, elevated activities of serum alkaline phosphatase and amylase, and hypoalbuminemia. No dogs seroreacted to Ehrlichia canis or Ehrlichia chaffeensis antigens, which are cross-reactive. Seventy-five percent of the dogs tested during the acute phase of disease and 100% of the dogs tested during convalescence were seropositive for E. equi antigens. Granulocytic ehrlichial 16S rRNA gene DNAs from six dogs were amplified by PCR. Sequence analysis of a 919-bp sequence of the ehrlichial 16S rRNA gene amplified by PCR from the blood of two dogs revealed the agent to be identical to the agent of human granulocytic ehrlichiosis in Minnesota and Wisconsin and to be very similar to E. equi and Ehrlichia phagocytophila and less similar to E. canis, Ehrlichia ewingii, and E. chaffeensis. The geographic, clinical, serologic, and molecular evidence indicates that granulocytic ehrlichiosis in Minnesota and Wisconsin dogs is not caused by E. ewingii, but suggests that it is a zoonotic disease caused by an agent closely related to E. equi and that dogs likely contribute to the enzootic cycle and human infection.


Strain Sensor via Wood Anomalies in 2D Dielectric Array.
Optical sensing is one of many promising applications for all-dielectric photonic materials. Herein, we present an analytical and numerical study on the strain-responsive spectral properties of a bioinspired sensor. The sensor structure contains a two-dimensional periodic array of dielectric nanodisks to mimic the optical behavior of grana lamellae inside chloroplasts. To accumulate a noticeable response, we exploit the collective optical mode in grana ensemble. In higher plants, such a mode appears as Wood's anomaly near the chlorophyll absorption line to control the photosynthesis rate. The resonance is shown persistent against moderate biological disorder and deformation. Under the stretching or compression of a symmetric structure, the mode splits into a couple of polarized modes. The frequency difference is accurately detected. It depends on the stretch coefficient almost linearly providing easy calibration of the strain-sensing device. The sensitivity of the considered structure remains at 5 nm/% in a wide range of strain. The influence of the stretching coefficient on the length of the reciprocal lattice vectors, as well as on the angle between them, is taken into account. This adaptive phenomenon is suggested for sensing applications in biomimetic optical nanomaterials.


SedNMR: on the edge between solution and solid-state NMR.
Solid-state NMR (SS-NMR) of proteins requires that those molecules be immobilized, usually by crystallization, freezing, or lyophilization. However, self-crowding can also slow molecular rotation sufficiently to prevent the nuclear interactions from averaging. To achieve self-crowding, researchers can use a centrifugal field to create a concentration gradient or use regular ultracentrifugation to produce highly concentrated, gel-like solutions. Thus sedimented solute NMR (SedNMR) provides a simple method to prepare biological samples for SS-NMR experiments with minimal perturbation. This method may also give researchers a way to investigate species that are not otherwise accessible by NMR. We induce the sedimentation in one of two ways: (1) by the extreme centrifugal force exerted during magic angle spinning (MAS-induced sedimentation or in situ) or (2) by an ultracentrifuge (UC-induced sedimentation or ex situ). Sedimentation is particularly useful in situations where it is difficult to obtain protein crystals. Furthermore, because the proteins remain in a largely hydrated state, the sedimented samples may provide SS-NMR spectra that have better resolution than the spectra from frozen solutions or lyophilized powders. If sedimentation is induced in situ, the same protein sample can be used for both solution and SS-NMR studies. Finally, we show that in situ SedNMR can be used to detect the NMR signals of large molecular adducts that have binding constants that are too weak to allow for the selective isolation and crystallization of the complexed species. We can selectively induce sedimentation for the heaviest molecular species. Because the complexed molecules are subtracted from the bulk solution, the reaction proceeds further toward the formation of complexes.


Ginsenoside-Rg5 Inhibits Retinoblastoma Proliferation and Induces Apoptosis through Suppressing BCL2 Expression.
Although the cure rate for retinoblastoma is high, surviving patients are at risk for developing secondary cancers and require life-long follow-up. It is imperative to discover and develop novel therapeutic agents with better efficiency and fewer adverse effects. Ginsenoside-Rg5 is an active derivate from ginseng and exerts anti-cancer activity in breast cancer cells. However, it is still unclear whether ginsenoside-Rg5 has similar anti-cancer functions in retinoblastoma. Retinoblastoma cells were treated with ginsenoside-Rg5, followed by MTT assay analysis of the cell viability, cell number assay and colony formation assay analyses of cell proliferation, and flow cytometric analysis of apoptosis. Gene mRNA levels and protein levels were determined by quantitative real-time PCR and Western blot, respectively. Ginsenoside-Rg5 inhibited retinoblastoma cell viability in a dose-dependent and time-dependent manner via preventing cell proliferation and inducing cell apoptosis. BCL2 expression was downregulated by ginsenoside-Rg5 treatment via inactivating the AKT signaling pathway. BCL2 overexpression completely eliminated the inhibitory effect of ginsenoside-Rg5 on cancer cell viability. Ginsenoside-Rg5 inhibits cell proliferation and induces apoptosis in retinoblastoma cells by inactivating the AKT signaling pathway, thereby downregulating BCL2 expression.


[Methyl-containing diet of mothers affects the AGOUTI gene expression in the offspring of rats with various behavioral types].
The effects of selection of agouti rats (with genotype AAHH) on the tame and aggressive behavior and dietary methyl given to females from the eighth day of pregnancy to the fifth day after the birth of the offspring on the intensity of the agouti coat color in the offspring have been studied. The morphometric parameters of hair determining the darkness of the agouti color (the total length of guard hairs, the lengths of their eumelanin end and pheomelanin band, the ratio between the lengths of the eumelanin and pheomelanin portions of the hair, the total length of the awn hairs, and the relative length of their widened "lanceolate" upper end) have been compared. It has been found that selection of agouti rats for aggressive behavior is accompanied by darkening of the coat color compared to tame rats due to an increase in the ratio of the length of the black eumelanin end of the guard hairs to the length of the yellow pheomelanin band. Methyl-containing additives to the diet of females affect the intensity of the agouti coat color in the offsprings with both types of behavior, but to different extents. Aggressive offspring is more sensitive to the mother's methyl-containing diet: the percentage of animals that are darker than control rats is higher among aggressive animals than among tame ones due to a greater increase in the ratio between dark and light portions of hairs. The possible mechanisms of differences in the phenotypic modifications of coat color in control and experimental agouti rats with different types of behavior are discussed.


Bidimensional focusing of x rays by refraction in an edge.
When an x-ray beam passes through the tip of a triangular prism, i.e., an edge, it undergoes two consecutive refraction processes. This will also happen when the incident beam is not perpendicular to the tip but when the beam progresses at a very small inclination to it. It will be shown that in such a condition, when both interfaces adjacent to the tip have concave surfaces, decoupled focusing in two orthogonal directions can be introduced in the transmitted x-ray beam. The limitations for this application are discussed, and focusing of x rays to spots with diffraction limited sizes of the order of 100 nanometers is found to be feasible. The feasibility of bidimensional focusing by use of such a device was experimentally verified.


Changing workload in ophthalmology: some observations from routine statistics.
Children with squints and old people with cataracts account for most of the work of ophthalmologists. Recent demographic changes have led to fewer children and more elderly patients needing treatment. So far the increased workload has been met by shortening the time patients spend in hospital, but with striking variations between districts.


Comparing effectiveness of top-down and bottom-up strategies in containing influenza.
This research compares the performance of bottom-up, self-motivated behavioral interventions with top-down interventions targeted at controlling an "Influenza-like-illness". Both types of interventions use a variant of the ring strategy. In the first case, when the fraction of a person's direct contacts who are diagnosed exceeds a threshold, that person decides to seek prophylaxis, e.g. vaccine or antivirals; in the second case, we consider two intervention protocols, denoted Block and School: when a fraction of people who are diagnosed in a Census Block (resp., School) exceeds the threshold, prophylax the entire Block (resp., School). Results show that the bottom-up strategy outperforms the top-down strategies under our parameter settings. Even in situations where the Block strategy reduces the overall attack rate well, it incurs a much higher cost. These findings lend credence to the notion that if people used antivirals effectively, making them available quickly on demand to private citizens could be a very effective way to control an outbreak.


Phenotypic and functional assessment of intraepithelial lymphocytes bearing a 'forbidden' alpha beta TCR.
Differences in the surface antigen phenotype, such as the expression CD8 as an alpha alpha homodimer or the lack of Thy-1, on intestinal intraepithelial lymphocytes (IEL) are related, in part, to alternative differentiation pathways. The relationship of IEL lacking the pan-T cell marker CD5 to these IEL, their TCR repertoire and function has not been examined directly. We explored the TCR repertoire and function of the CD5- IEL subset in relation to the expression of the 'autospecific' V beta 6 TCR in MIs-1a mice and to gamma delta TCR. The results indicate that CD5 expression was absent on the majority of TCR gamma delta IEL (96.9%) and on a significant proportion of TCR alpha beta IEL (25.0%). Virtually all IEL in DBA/2 (MIs-1a) mice that expressed the 'autospecific' V beta 6 TCR were CD5-, and this correlated with the expression of CD8 alpha alpha. To assess the functional capacity of this subset of IEL, we examined proliferation and IL-2 production in response to TCR activation. Although CD5- IEL proliferated in response to anti-CD3, IEL bearing TCR V beta 6, in MIs-1a mice, were not responsive to TCR-mediated activation. Similarly, TCR gamma delta IEL were not responsive to stimulation by anti-TCR gamma delta antibodies. The addition of exogenous IL-2, however, reconstituted the proliferative response of both TCR gamma delta IEL and the TCR V beta 6 expressing IEL. We conclude that the lack of CD5 defines a unique subset of intraepithelial T cells expressing either TCR gamma delta or alpha beta that include potentially autoreactive cells that remain anergic in the absence of IL-2.


Outpatient physiotherapy versus home-based rehabilitation for patients at risk of poor outcomes after knee arthroplasty: CORKA RCT.
Over 100,000 primary knee arthroplasty operations are undertaken annually in the UK. Around 15-30% of patients do not report a good outcome. Better rehabilitation strategies may improve patient-reported outcomes. To compare the outcomes from a traditional outpatient physiotherapy model with those from a home-based rehabilitation programme for people assessed as being at risk of a poor outcome after knee arthroplasty. An individually randomised, two-arm controlled trial with a blinded outcome assessment, a parallel health economic evaluation and a nested qualitative study. The trial took place in 14 NHS physiotherapy departments. People identified as being at high risk of a poor outcome after knee arthroplasty. A multicomponent home-based rehabilitation package delivered by rehabilitation assistants with supervision from qualified therapists compared with usual-care outpatient physiotherapy. The primary outcome was the Late Life Function and Disability Instrument at 12 months. Secondary outcomes were the Oxford Knee Score (a disease-specific measure of function); Knee injury and Osteoarthritis Outcome Score; Quality of Life subscale; Physical Activity Scale for the Elderly; EuroQol-5 Dimensions, five-level version; and physical function assessed using the Figure-of-8 Walk Test, 30-Second Chair Stand Test and Single Leg Stance. Data on the use of health-care services, time off work and informal care were collected using participant diaries. In total, 621 participants were randomised. A total of 309 participants were assigned to the COmmunity based Rehabilitation after Knee Arthroplasty (CORKA) home-based rehabilitation programme, receiving a median of five treatment sessions (interquartile range 4-7 sessions). A total of 312 participants were assigned to usual care, receiving a median of four sessions (interquartile range 2-6 sessions). The primary outcome, Late Life Function and Disability Instrument function total score at 12 months, was collected for 279 participants (89%) in the home-based CORKA group and 287 participants (92%) in the usual-care group. No clinically or statistically significant difference was found between the groups (intention-to-treat adjusted difference 0.49 points, 95% confidence interval -0.89 to 1.88 points; p = 0.48). There were no statistically significant differences between the groups in any of the patient-reported or physical secondary outcome measures at 6 or 12 months post randomisation. The health economic analysis found that the CORKA intervention was cheaper to provide than usual care (£66 less per participant). Total societal costs (combining health-care costs and other costs) were lower for the CORKA intervention than usual care (£316 less per participant). Adopting a societal perspective, CORKA had a 75% probability of being cost-effective at a threshold of £30,000 per quality-adjusted life-year. Adopting the narrower health and social care perspective, CORKA had a 43% probability of being cost-effective at the same threshold. The interventions were of short duration and were set within current commissioning guidance for UK physiotherapy. Participants and treating therapists could not be blinded. This randomised controlled trial found no important differences in outcomes when post-arthroplasty rehabilitation was delivered using a home-based, rehabilitation assistant-delivered rehabilitation package or a traditional outpatient model. However, the health economic evaluation found that when adopting a societal perspective, the CORKA home-based intervention was cost-saving and more effective than, and thus dominant over, usual care, owing to reduced time away from paid employment for this group. Further research could look at identifying the risk of poor outcome and further evaluation of a cost-effective treatment, including the workforce model to deliver it. Current Controlled Trials ISRCTN13517704. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 65. See the NIHR Journals Library website for further project information.


Flexible NO(x) abatement from power plants in the eastern United States.
Emission controls that provide incentives for maximizing reductions in emissions of ozone precursors on days when ozone concentrations are highest have the potential to be cost-effective ozone management strategies. Conventional prescriptive emissions controls or cap-and-trade programs consider all emissions similarly regardless of when they occur, despite the fact that contributions to ozone formation may vary. In contrast, a time-differentiated approach targets emissions reductions on forecasted high ozone days without imposition of additional costs on lower ozone days. This work examines simulations of such dynamic air quality management strategies for NO(x) emissions from electric generating units. Results from a model of day-specific NO(x) pricing applied to the Pennsylvania-New Jersey-Maryland (PJM) portion of the northeastern U.S. electrical grid demonstrate (i) that sufficient flexibility in electricity generation is available to allow power production to be switched from high to low NO(x) emitting facilities, (ii) that the emission price required to induce EGUs to change their strategies for power generation are competitive with other control costs, (iii) that dispatching strategies, which can change the spatial and temporal distribution of emissions, lead to ozone concentration reductions comparable to other control technologies, and (iv) that air quality forecasting is sufficiently accurate to allow EGUs to adapt their power generation strategies.


Parallax and atmospheric scattering effects on the inversion of satellite auroral observations.
A technique for the inversion of satellite auroral brightness observations is developed, which takes into account the backscattering of light from the snow-covered ground and atmospheric scattering. The theory includes parallax effects. Parallax arises when a point in the aurora is observed from different angles against a background with a variable brightness. It is shown that observations from a spinning satellite at any given angle from nadir are sufficient to recover the auroral form.


A Dual Model of Leadership and Hierarchy: Evolutionary Synthesis.
From the popularity of authoritarian political leaders to the under-representation of women in boardrooms, leadership is an important theme in current human social affairs. Leadership is also a prominent research topic in the biological, social, and cognitive sciences. However, these active literatures have evolved somewhat independently and there is a need for synthesis. A comparative-evolutionary approach can integrate seemingly divergent perspectives by making a distinction between two leadership styles, prestige and dominance, that have contrasting expressions, functions, histories, and neural and developmental pathways. The distinction may help to resolve various scientific puzzles, such as: (i) opposing views on the different functions and expressions of leadership; (ii) the appeal of dominance-style leaders; and (iii) sex biases in leadership emergence in modern society.


Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation.
The glycosylphosphatidylinositol (GPI)-anchored proteoglycan Cripto binds Nodal and its type I receptor Alk4 to activate Smad2,3 transcription factors, but a role during Nodal precursor processing has not been described. We show that Cripto also binds the proprotein convertases Furin and PACE4 and localizes Nodal processing at the cell surface. When coexpressed as in early embryonic cells, Cripto and uncleaved Nodal already associated during secretion, and a Cripto-interacting region in the Nodal propeptide potentiated the effect of proteolytic maturation on Nodal signalling. Disruption of the trans-Golgi network (TGN) by brefeldin A blocked secretion, but export of Cripto and Nodal to the cell surface was not inhibited, indicating that Nodal is exposed to extracellular convertases before entering the TGN/endosomal system. Density fractionation and antibody uptake experiments showed that Cripto guides the Nodal precursor in detergent-resistant membranes to endocytic microdomains marked by GFP-Flotillin. We conclude that Nodal processing and endocytosis are coupled in signal-receiving cells.


Sustaining a coordinated, regional approach to trauma and emergency care is critical to patient health care needs.
Trauma systems provide an organized approach to the care of injured patients within a defined geographic region. When fully operational, the systems ensure a continuum of care involving public access through 911 calls, emergency medical services, timely triage and transport to acute care, and transfer to rehabilitation services. Substantial progress has been made in establishing statewide trauma systems, which are seen as the prototype for regionalized care for other time-sensitive, emergency conditions such as stroke. Trauma systems provide a model of care that is consistent with the goals of the Affordable Care Act, which authorizes $100 million in annual grants to ensure the continued availability of trauma services. Full funding of these provisions is needed to stabilize statewide systems that are struggling to survive. We describe the components of a regionalized trauma system, review the evidence in support of this approach, and discuss the challenges to sustaining systems that are accountable and affordable.


A fucoidan from sea cucumber Pearsonothuria graeffei with well-repeated structure alleviates gut microbiota dysbiosis and metabolic syndromes in HFD-fed mice.
A high-fat diet (HFD) has been a major contributor to increasing morbidity caused by metabolic syndromes. Functional foods from natural sources are potential choices for addressing metabolic diseases because they provide many health benefits with a low level of adverse side effects. In our former reports, fucoidan from Pearsonothuria graeffei (fuc-Pg), a type of sulfated polysaccharides with a repeating structure, was shown to be a potential functional food ingredient. In this work, we investigated the effects of fuc-Pg on gut microbiota dysbiosis and metabolic syndromes caused by HFD. Our results indicated that fuc-Pg could reduce weight gains, alleviate hyperlipidemia, and protect the liver from steatosis in HFD-fed mice. Meanwhile, fuc-Pg decreases serum inflammatory cytokines and reduces macrophages infiltrating into adipose tissue. The gut microbiota dysbiosis caused by HFD was alleviated by administration of fuc-Pg, mainly working in the colon. Fuc-Pg increased abundances of Bacteroidetes and Actinobacteria while decreased Firmicutes and Proteobacteria. Our results indicated that fuc-Pg could be a functional food for gut microbiota dysbiosis and metabolic syndromes.


Comprehensive composition of Creosote using comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS).
Creosote is a distillation product of coal tar and is widely used as wood preservative for railway sleepers, utility poles and for other applications. Creosote can have potentially negative effects on the environment and many of the components are toxic. This study presents the analysis of a Creosote sample from a former wood impregnation plant located in the UK. The sample was analysed using two dimensional gas chromatography time-of-flight mass spectrometry (GCxGC-TOFMS) and a database of compounds that could be detected was produced. The GCxGG-TOFMS was capable of detecting 1505 individual compounds, which is far more than previous estimates for the number of compounds present within Creosote. Post extraction derivatization using BTSFA with 1% TMCS was employed to increase the potential number of compounds detected with 255 derivatized compounds detected, 231 of which would not have been detected without prior derivatization. Selected derivatized compounds were quantified with limits of detection ranging from 0.6 mg/kg to 1.6 mg/kg from a concentrated dense non-aqueous phase liquid (DNAPL). This work presents the first published full analysis of a Creosote using GCxGC-TOFMS combined with derivatization.


RNA silencing of mycotoxin production in Aspergillus and Fusarium species.
Mycotoxins are natural fungal products that are defined by their harmful effects on humans and animals. Aflatoxin contamination of maize by Aspergillus species and trichothecene contamination of small grains by Fusarium species are two of the most severe mycotoxin problems in the United States. We are investigating RNA silencing in an effort to identify novel ways to control mycotoxin contamination of crops. Transformation of two Aspergilli (A. flavus and A. parasiticus) and a Fusarium (F. graminearum) with inverted repeat transgenes (IRT) containing sequences of mycotoxin-specific regulatory genes suppressed mycotoxin production in all three plant-pathogenic fungi. This atoxigenic phenotype was stable during infection on corn and wheat, and importantly, F. graminearum IRT strains were less virulent on wheat than were wild type. The IRT did not alter physiological characteristics of the fungi, such as spore production and growth rate on solid media. These results indicate that RNA silencing exists in Aspergillus and Fusarium plant pathogens and suggest that RNA silencing technology may be a useful tool for eliminating mycotoxin contamination of agricultural products.


Toxoplasmosis in HIV infection: An overview.
Toxoplasma gondii is an obligate intracellular protozoan parasite presenting as a zoonotic infection distributed worldwide. In HIV-positive individuals, it causes severe opportunistic infections, which is of major public health concern as it results in physical and psychological disabilities. In healthy immunocompetent individuals, it causes asymptomatic chronic persistent infections, but in immunosuppressed patients, there is reactivation of the parasite if the CD4 counts fall below 200 cells/μl. The seroprevalence rates are variable in different geographic areas. The tissue cyst or oocyst is the infective form which enters by ingestion of contaminated meat and transform into tachyzoites and disseminate into blood stream. In immunocompetent persons due to cell-mediated immunity the parasite is transformed into tissue cyst resulting in life long chronic infection. In HIV-infected people opportunistic infection by T. gondii occurs due to depletion of CD4 cells, decreased production of cytokines and interferon gamma and impaired cytotoxic T-lymphocyte activity resulting in reactivation of latent infection. The diagnosis can be done by clinical, serological, radiological, histological or molecular methods, or by the combination of these. There is various treatment regimen including acute treatment, maintenance therapy should be given as the current anti T. gondii therapy cannot eradicate tissue cysts. In HIV patients, CD4 counts <100; cotrimoxazole, alternately dapsone + pyrimethamine can be given for 6 months. Hence, early diagnosis of T. gondii antibodies is important in all HIV-positive individuals to prevent complications of cerebral toxoplasmosis.


Association between Obstructive Sleep Apnea and Acute Kidney Injury in Critically Ill Patients: A Propensity-Matched Study.
Obstructive sleep apnea (OSA) is a known risk factor for chronic kidney disease (CKD); however, its association with acute kidney injury (AKI) is not well documented. We aimed to study whether OSA is associated with the risk of AKI in the intensive care unit (ICU) setting. All consecutive adult Olmsted County, MN residents who were admitted in Mayo Clinic ICUs from January 1, 2010 to December 31, 2010 were screened. Chronic and acute risk factors were collected within the first 48 h of ICU admission. Logistic regression and propensity score matching were used to examine crude and adjusted associations of OSA with AKI. Among 1,259 enrolled ICU patients, 183 patients had a diagnosis of OSA prior to the index ICU admission. Compared with non-OSA patients, the incidence of AKI in OSA patients was more frequent (41 vs. 57%, p < 0.001). In univariate analysis, it was found that CKD, age, gender, Caucasian race, congestive heart failure, cerebrovascular disease, diabetes mellitus, body mass index, and OSA were associated with AKI. In the multivariate model, following adjustment for age, gender, race, and chronic and acute risk factors, OSA was found to have an independent association with AKI (OR 1.53; 95% CI 1.04-2.24; p = 0.031). Among 176 propensity score matched pairs, there was a significant difference in the incidence of AKI between the OSA and non-OSA groups (OR 1.54; 95% CI 1.01-2.35; p = 0.04). The history of OSA diagnosed by polysomnography is associated with higher risk of AKI in critically ill patients.


Diet composition, food intake, apparent digestibility, and body condition score of the captive Asian elephant (Elephas maximus): a pilot study in two collections in Thailand.
Limited data are available regarding the nutrition and feeding of captive Asian elephants in range countries. In this study, feeding regimens of two collections in northern Thailand and their actual diets shaped by availability of forage and mahout preferences were assessed for nutritional quality. The composition of dietary intake, fecal output, and the dietary regimen were individually recorded for 5 days in 10 elephants. The proportion of forage in the diet represented 41 to 62% of the dry matter intake (DMI) in one collection whereas in the other collections it varied between 68 and 72%. Between 8.5 and 24% of the diet consisted of commercial pellets, and hulled rice represented up to 25% of the DMI in one collection. Sugar cane, corn cobs, and fruits such as bananas were eaten in smaller amounts. Body condition scores and weights were measured, which revealed that nine animals were in good condition. Representative samples of each food as well as fecal samples were analyzed for dry matter, crude protein, fat, crude fiber, gross energy, ash, calcium, and phosphorus. Diet adequacy was assessed by calculating the digestible nutrients in the rations and by comparing them to the recommendations from literature. The digestible energy (DE) intake varied between 0.6 and 1.4 megajoules (MJ) per kg(0.75) per day; therefore, higher than the estimated recommendations of 0.65 MJ per kg(0.75) per day for nine of the elephants. In all elephants the crude protein intake was less than the maintenance recommendations and ranged between 6.01 and 7.56% of the DMI. Calcium intake was low in one collection and there was an inverse calcium: phosphorus ratio, which was inadequate. The present study adds to the knowledge of captive elephant diets in Asia and is a starting point for further research, which is necessary to design optimum diet plans for captive Asian elephants in Thailand.


18F-FDG PET/CT metabolic tumor volume and total lesion glycolysis predict outcome in oropharyngeal squamous cell carcinoma.
Treatment of oropharyngeal squamous cell carcinoma with chemoradiotherapy can now accomplish excellent locoregional disease control, but patient overall survival (OS) remains limited by development of distant metastases (DM). We investigated the prognostic value of staging (18)F-FDG PET/CT, beyond clinical risk factors, for predicting DM and OS in 176 patients after definitive chemoradiotherapy. The PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded. Univariate Cox regression was used to examine the prognostic value of these variables and clinical prognosticators for local treatment failure (LTF), OS, and DM. Multivariate analysis examined the effect of SUVmax, TLG, and MTV in the presence of other covariates. Kaplan-Meier curves were used to evaluate prognostic values of PET/CT parameters. Primary tumors were distributed across all stages. Most patients underwent chemoradiotherapy only, and 11 also underwent tonsillectomy. On univariate analysis, primary tumor MTV was predictive of LTF (P = 0.005, hazard ratio [HR] = 2.4 for a doubling of MTV), DM and OS (P < 0.001 for both, HR = 1.9 and 1.8, respectively). The primary tumor TLG was associated with DM and OS (P < 0.001, HR = 1.6 and 1.7, respectively, for a doubling of TLG). The primary tumor SUVmax was associated with death (P = 0.029, HR = 1.1 for a 1-unit increase in standardized uptake value) but had no relationship with LTF or DM. In multivariate analysis, TLG and MTV remained associated with death after correcting for T stage (P = 0.0125 and 0.0324, respectively) whereas no relationship was seen between standardized uptake value and death after adjusting for T stage (P = 0.158). Parameters capturing the volume of (18)F-FDG-positive disease (MTV or TLG) provide important prognostic information in oropharyngeal squamous cell carcinoma treated with chemoradiotherapy and should be considered for risk stratification in this disease.


The effects of cimetidine, ranitidine, and famotidine on human neutrophil functions.
Neutrophil functions, which play an important role in the antibacterial host defense system, are inhibited by various anesthetics and surgical procedures. Histamine H2-receptor antagonists are perioperatively used as a prophylaxis against acid aspiration syndrome or stress ulceration. We examined the effect of cimetidine, ranitidine, and famotidine, at clinically relevant concentrations and at 10 and 100 times this concentration, on several aspects of human neutrophil function using an in vitro system. The three H2-receptor antagonists did not impair neutrophils' chemotaxis or phagocytosis. Cimetidine and famotidine inhibited superoxide (O2-) and hydrogen peroxide (H2O2) production of the neutrophils in a dose-dependent manner, although the inhibitory effects were minimal. In contrast, ranitidine failed to change O2- or H2O2 production of neutrophils. The three H2-receptor antagonists did not scavenge these reactive oxygen species generated by the xanthine-xanthine oxidase system. The increase in intracellular calcium concentrations in neutrophils by a stimulant were dose-dependently attenuated with cimetidine or famotidine. This decreasing effect of the drugs on [Ca2+]i in neutrophils may represent one of mechanisms responsible for inhibition of reactive oxygen species generation. Neutrophils play a pivotal role in the antibacterial host defense system and tissue injury. We found that cimetidine and famotidine slightly reduced the O2- or H2O2 production of neutrophils in a dose-dependent manner, although ranitidine failed to do so. At least ranitidine does not seem to have any deleterious effect on neutrophil function, which is clearly an important consideration in its use in severely ill patients.


Distribution of mercury and methylmercury in surface water and surface sediment of river, irrigation canal, reservoir, and wetland in Taiwan.
In Taiwan, because of the co-use of some irrigation and drainage canals, a portion of industrial wastewater was directly discharged into irrigation canals or even flowed into rivers or wetlands, causing the heavy metal pollution in waters and sediments. Mercury (Hg) contamination in rivers, irrigation canals, and wetlands has been found in Taiwan, but a thorough investigation on the distribution of Hg and methylmercury (MeHg) in these waters and sediments, which may be present in a greater level with elevating total Hg (THg) concentration and markedly impact human health, is still lacking. In this study, surface waters and surface sediments were sampled from five major rivers, two irrigation canals, two reservoirs, and one wetland in Taiwan, and their THg and MeHg concentrations were quantified. Additionally, statistical analysis was carried out to understand the relationship between sediment properties and MeHg levels. The results showed that irrigation canal sediments were relatively more polluted by Hg and the THg concentrations of some sampling points exceeded the upper limit (i.e., 0.87 mg kg-1) of sediment quality index (SQI) for THg promulgated by Taiwan Environmental Protection Administration, which may be attributed to the co-use of irrigation and drainage canals. Furthermore, the MeHg concentration in irrigation canal sediments was the highest; rivers came in second followed by wetlands. In addition, the Siangshan Wetland was analyzed to have the greatest THg and MeHg concentrations in its surface water. Linear regression analysis also indicated that total organic carbon and clay content substantially affected the MeHg production in sediments.


A Comparison of Predictive Performances between Old versus New Criteria in a Risk-Based Screening Strategy for Gestational Diabetes Mellitus.
The definition of the high-risk group for gestational diabetes mellitus (GDM) defined by the American College of Obstetricians and Gynecologists was changed from the criteria composed of five historic/demographic factors (old criteria) to the criteria consisting of 11 factors (new criteria) in 2017. To compare the predictive performances between these two sets of criteria. This is a secondary analysis of a large prospective cohort study of non-diabetic Korean women with singleton pregnancies designed to examine the risk of GDM in women with nonalcoholic fatty liver disease. Maternal fasting blood was taken at 10 to 14 weeks of gestation and measured for glucose and lipid parameters. GDM was diagnosed by the two-step approach. Among 820 women, 42 (5.1%) were diagnosed with GDM. Using the old criteria, 29.8% (n=244) of women would have been identified as high risk versus 16.0% (n=131) using the new criteria. Of the 42 women who developed GDM, 45.2% (n=19) would have been mislabeled as not high risk by the old criteria versus 50.0% (n=21) using the new criteria (1-sensitivity, 45.2% vs. 50.0%, P>0.05). Among the 778 patients who did not develop GDM, 28.4% (n=221) would have been identified as high risk using the old criteria versus 14.1% (n=110) using the new criteria (1-specificity, 28.4% vs. 14.1%, P<0.001). Compared with the old criteria, use of the new criteria would have decreased the number of patients identified as high risk and thus requiring early GDM screening by half (from 244 [29.8%] to 131 [16.0%]).


Localization of cortical tissue optical changes during seizure activity in vivo with optical coherence tomography.
Optical coherence tomography (OCT) is a high resolution, minimally invasive imaging technique, which can produce depth-resolved cross-sectional images. In this study, OCT was used to detect changes in the optical properties of cortical tissue in vivo in mice during the induction of global (pentylenetetrazol) and focal (4-aminopyridine) seizures. Through the use of a confidence interval statistical method on depth-resolved volumes of attenuation coefficient, we demonstrated localization of regions exhibiting both significant positive and negative changes in attenuation coefficient, as well as differentiating between global and focal seizure propagation.


Automatic quantification of aortic regurgitation using 3D full volume color doppler echocardiography: a validation study with cardiac magnetic resonance imaging.
Recent advances in real-time three-dimensional (3D) echocardiography provide the automated measurement of mitral inflow and aortic stroke volume without the need to assume the geometry of the heart. The aim of this study is to explore the ability of 3D full volume color Doppler echocardiography (FVCDE) to quantify aortic regurgitation (AR). Thirty-two patients with more than a moderate degree of AR were enrolled. AR volume was measured by (1) two-dimensional-CDE, using the proximal isovelocity surface area (PISA) and (2) real-time 3D-FVCDE with (3) phase-contrast cardiac magnetic resonance imaging (PC-CMR) as the reference method. Automated AR quantification using 3D-FVCDE was feasible in 30 of the 32 patients. 2D-PISA underestimated the AR volume compared to 3D-FVCDE and PC-CMR (38.6 ± 9.9 mL by 2D-PISA; 49.5 ± 10.2 mL by 3D-FVCDE; 52.3 ± 12.6 mL by PC-CMR). The AR volume assessed by 3D-FVCDE showed better correlation and agreement with PC-CMR (r = 0.93, p < 0.001, 2SD: 9.5 mL) than did 2D-PISA (r = 0.76, p < 0.001, 2SD: 15.7 mL). When used to classify AR severity, 3D-FVCDE agreed better with PC-CMR (k = 0.94) than did 2D-PISA (k = 0.53). In patients with eccentric jets, only 30% were correctly graded by 2D-PISA. Conversely, almost all patients with eccentric jets (86.7%) were correctly graded by 3D-FVCDE. In patients with multiple jets, only 3 out of 10 were correctly graded by 2D-PISA, while 3D-FVCDE correctly graded 9 out of 10 of these patients. Automated quantification of AR using the 3D-FVCDE method is clinically feasible and more accurate than the current 2D-based method. AR quantification by 2D-PISA significantly misclassified AR grade in patients with eccentric or multiple jets. This study demonstrates that 3D-FVCDE is a valuable tool to accurately measure AR volume regardless of AR characteristics.


Managed care and dually eligible beneficiaries: challenges in coordination.
This article describes administrative issues and beneficiary perspectives on the delivery of medical services under Medicare+Choice (M+C) and/or Medicaid managed care organizations (MCOs) for dually eligible beneficiaries. We interviewed staff at nine health plans in four market areas in 2000 and 2001, and conducted beneficiary focus groups in 2001. The study reveals beneficiary confusion about the relationship between their dual coverage and managed care enrollment, and problems with care and benefit coordination across these arrangements, based on regulatory and administrative obstacles to effective benefit and care coordination for beneficiaries enrolled in these varied managed care arrangements.


The known unknowns of perioperative stroke during carotid body tumour resection.
Carotid body tumour (CBT) surgery has a risk of stroke. A 57-year-old lady presented with lethargy and generalised limb pain secondary to a right parathyroid adenoma. CT scan demonstrated as an incidental finding of a left CBT. Intraoperatively the CBT was infiltrating the vessel wall. The carotid bifurcation was resected and reconstructed using a reversed saphenous vein graft. Postoperatively the patient developed right arm weakness. A CT scan showed a left hemispheric watershed infarct. On discharge (day 8 postoperatively) she had no functional deficit. Reconstruction of the internal carotid artery in patients with CBT is associated with an increased risk of stroke. This index case and literature research highlight the knowns and unknowns on stroke associated with CBT resection.


Effects of Theophylline with Methylprednisolone Combination Therapy on Biomechanics and Histopathology in Diaphragm Muscles of Rats.
The purpose of this study was to investigate the effects of theophylline and methylprednisolone on the mechanical response and histopathology of hemidiaphragm muscle in rats. In the current study, we aimed to investigate the effects of theophylline and methylprednisolone, which are frequently used in clinics and which have different effects on the respiratory system and on the biomechanics and histopathology of the diaphragm muscle. The study included four groups of rats. Group T received 1 mg/kg of intraperitoneal theophylline, group M received 2 mg/kg of intraperitoneal methylprednisolone, group TM received 1 mg/kg of intraperitoneal theophylline plus 2 mg/kg of intraperitoneal methylprednisolone, and group K received of 1 mL intraperitoneal isotonic solution (of 0.9 % NaCl). The medications were continued for 7 days in each group. The rats underwent cervical dislocation under anesthesia on the eighth day, and their diaphragm samples were extracted. The left hemidiaphragm was used for the investigation of biomechanical parameters, and the right hemidiaphragm was used for the histopathological evaluation. It was observed that the medication administered in group T increased the contraction strength and duration compared with that in group M. Additionally, the duration of semi-relaxation was prolonged in group T compared with group M. The highest contraction strength and the longest contraction period among all of the groups were observed in group TM. It was concluded that the combined use of theophylline and methylprednisolone had positive effects on the contraction strength and the durations of contraction and semi-relaxation of the diaphragm muscle. In addition, both drugs had synergistic effects on each other.


Perioperative prophylactic middle meningeal artery embolization for chronic subdural hematoma: a series of 44 cases.
Chronic subdural hematoma (cSDH) is a common and challenging pathology to treat due to both the historically high recurrence rate following surgical evacuation and the medical comorbidities inherent in the aging patient population that it primarily affects. Middle meningeal artery (MMA) embolization has shown promise in the treatment of cSDHs, most convincingly to avoid surgical evacuation in relatively asymptomatic patients. Symptomatic patients requiring surgical evacuation may also benefit from perioperative MMA embolization to prevent cSDH recurrence. The goal of this study was to determine the utility of perioperative MMA embolization for symptomatic cSDH requiring surgical evacuation and to assess if there is a decrease in the cSDH recurrence rate compared to historical recurrence rates following surgical evacuation alone. Symptomatic cSDHs were evacuated using a subdural evacuating port system (SEPS) with 5-mm twist-drill craniostomy in an intensive care unit or by performing a craniotomy in the operating room, using either a small (silver dollar, < 4 cm) or large (≥ 4 cm) craniotomy. MMA embolization was performed perioperatively using angiography, selective catheterization of the MMA, and infusion of polyvinyl particles. Outcomes were assessed clinically and radiographically with interval head CT imaging. There were 44 symptomatic cSDHs in 41 patients, with 3 patients presenting with bilateral symptomatic cSDH. All cSDHs were evacuated using an SEPS (n = 18), a silver-dollar craniotomy (n = 16), or a large craniotomy (n = 10). Prophylactic MMA embolization was performed successfully in all cSDHs soon after surgical evacuation. There were no deaths and no procedural complications. There was an overall reduction of greater than 50% or resolution of cSDH in 40/44 (90.9%) cases, regardless of the evacuation procedure used. Of the 44 prophylactic cases, there were 2 (4.5%) cases of cSDH recurrence that required repeat surgical evacuation at the 1-year follow-up. These 2 cSDHs were initially evacuated using an SEPS and subsequently required a craniotomy, thereby representing an overall 4.5% recurrence rate of treated cSDH requiring repeat evacuation. Most notably, of the 26 patients who underwent surgical evacuation with a craniotomy followed by MMA embolization, none had cSDH recurrence requiring repeat intervention. Perioperative prophylactic MMA embolization in the setting of surgical evacuation, via either craniotomy or SEPS, may help to lower the recurrence rate of cSDH.