Connectivity-based parcellation of normal and anatomically distorted human cerebral cortex.
For over a century, neuroscientists have been working toward parcellating the human cortex into distinct neurobiological regions. Modern technologies offer many parcellation methods for healthy cortices acquired through magnetic resonance imaging. However, these methods are suboptimal for personalized neurosurgical application given that pathology and resection distort the cerebrum. We sought to overcome this problem by developing a novel connectivity-based parcellation approach that can be applied at the single-subject level. Utilizing normative diffusion data, we first developed a machine-learning (ML) classifier to learn the typical structural connectivity patterns of healthy subjects. Specifically, the Glasser HCP atlas was utilized as a prior to calculate the streamline connectivity between each voxel and each parcel of the atlas. Using the resultant feature vector, we determined the parcel identity of each voxel in neurosurgical patients (n = 40) and thereby iteratively adjusted the prior. This approach enabled us to create patient-specific maps independent of brain shape and pathological distortion. The supervised ML classifier re-parcellated an average of 2.65% of cortical voxels across a healthy dataset (n = 178) and an average of 5.5% in neurosurgical patients. Our patient dataset consisted of subjects with supratentorial infiltrating gliomas operated on by the senior author who then assessed the validity and practical utility of the re-parcellated diffusion data. We demonstrate a rapid and effective ML parcellation approach to parcellation of the human cortex during anatomical distortion. Our approach overcomes limitations of indiscriminately applying atlas-based registration from healthy subjects by employing a voxel-wise connectivity approach based on individual data.


[Drug resistance evolution of dichlorvos-resistant and cypermethrin-resistant strains of Culex pipiens pallens].
Susceptible strain of Culex pipiens pallens was selected with dichlorvos and cypermethrin for 42 generations in the laboratory. At generation 42, the resistance level to dichlorvos and cypermethrin was 12.2-fold and 534.3-fold, respectively, in comparison to their parent generations. The dichlorvos-resistant and cypermethrin-resistant strains were then conventionally bred for another 20 generations, the resistance level to dichlorvos and cypermethrin decreased to 6.1-fold and 83.3-fold, respectively. The results indicated that the two resistant strains showed different development of resistance.


[Electrogenic function of submitochondrial particles at the water-octane interphases].
Studies on submitochondrial particles (SMP) preparation showed that in the sourse of the redox reactions at the octane-water interface, catalyzed by SMP enzymes, the charges are transferred from the aqueous to the octane phase. The effects were detected by a shift of the Volta potential, using the vibrating electrode method. In the presence of 2-N-methyl-amino-1,4-naphthoquinone in octane, acting as electron acceptor, the negative charges were transferred from water to octane following the oxidation of NADH, succinate and ascorbate. The charging of the octane phase was sensitive to the inhibitors of the respiratory chain, e. g. rotenone, antimycin and cyanide. In the presence of 2,4-DNP in octane, acting as a proton acceptor, the oxidation of NADH and succinate by ferricyanide, catalyzed by CMP in the presence of antimycin and cyanide correspondingly, was followed by a transfer of positive charges from water to octane. The positive charging of the octane phase, coupled with NADH oxidation, was found insensitive to rotenone, and that coupled with succinate oxidation, was completely inhibited by antimycin. The positive charging of the octane phase was also observed during the reverse transhydrogenase reaction, catalyzed by SMP at the division of the phases. The effect was inhibited by palmitoyl-CoA.


Significance of osteopontin in the sensitivity of malignant pleural mesothelioma to pemetrexed.
Pemetrexed (PEM) is currently recommended as one of the standard anticancer drugs for malignant pleural mesothelioma (MPM). However, the mechanism of the sensitivity of MPM to PEM remains unclear. We analyzed the antitumor effects of PEM in six MPM cell lines by MTS assay. To identify genes associated with drug sensitivity, we conducted gene expression profiling on the same set of cell lines using GeneChips and pathway analysis. Three cell lines were sensitive to PEM. A total fo 18 transcripts and 14 genes identified by GeneChips were significantly correlated with sensitivity to PEM. Pathway analysis revealed that osteopontin (SPP1/OPN) was an important target in PEM sensitivity. Overexpression of SPP1/OPN was observed in the sensitive cells by quantitative PCR and western blot analysis. Introduction of SPP1/OPN by lentiviral vector significantly enhanced the invasion activities of MPM cells. PEM treatment with SPP1/OPN knockdown inhibited the PEM-induced cell growth-inhibitory effect in PEM-sensitive cells. Expression of SPP1/OPN and AKT phosphorylation significantly decreased after PEM treatment of the PEM-sensitive cells. High immunohistochemical expression of SPP1/OPN was observed in two of three MPM patients who had a partial response to PEM-based chemotherapy. PEM has antitumor effects in MPM cells dependent on SPP1/OPN overexpression resulting in AKT activation. Our results suggest that SPP1 may be used as a single predictive biomarker of the effectiveness of PEM treatment in MPM.


[Specificity of liposome uptake from target cell lipids].
A more considerable uptake of liposomes (1.5-2 times greater) from lipids of target cells was revealed in the cells of ascites lympholeukemia NKLy/LL and Ehrlich's ascites carcinoma as compared with liposomes from other tumor lipids. NKLy/LL cells uptake liposomes from their own lipids 8 times as effective, whereas Ehrlich's carcinoma cells 3 times as effective as widely applied vesicles from egg lecithin. Evidence is provided that the differences discovered are consequent on the different mechanisms of liposome interaction with the cells. As far as egg lecithin is concerned, the principal mechanism of interaction is endocytosis which is unmarked in these cells. Meanwhile uptake of target cell lipids is effected by the fusion mechanism.


Rational design of high performance surface plasmon resonance sensors based on two-dimensional metallic hole arrays.
We have rationally designed two-dimensional Au and Ag hole arrays for high performing surface plasmon resonance (SPR) sensing. The figure-of-merit (FOM), which is defined as sensitivity/linewidth, is found to be highly geometry-dependent. For sensitivity, we find it is equal to the period of array when exciting low order surface plasmon modes at low incident angle. Therefore, increasing period improves sensitivity. On the other hand, narrow linewidth can be obtained from small hole size so that the radiative decay loss is minimized. By using a pair of orthogonally oriented polarizer and analyzer, the signal-to-noise ratio (SNR) can be greatly enhanced due to the elimination of the nonresonant reflection background. As a proof of our strategy, we have obtained FOM larger than 100/RIU and SNR higher than 110 from Au arrays. Our results show the importance of understanding the basic properties of surface plasmon polaritons in order to systematically optimize the performance of the plasmonic system for a given application.


Electrochemical Sandwich Immunosensor for Determination of Exosomes Based on Surface Marker-Mediated Signal Amplification.
Extracellular vesicles (EVs), namely, exosomes and microvesicles, are important mediators of intercellular communication pathways. Since EVs can be detected in a variety of biofluids and contain a specific set of biomarkers which are reminiscent of their parental cells, they show great promise in clinical diagnostics as EV analysis can be performed in minimally invasive liquid biopsies. However, reliable, fast and cost-effective methods for their determination are still needed, especially if decentralized analysis is intended. In this study, we developed an electrochemical biosensor which works with 1.5 μL sample volume and can detect as low as 200 exosomes per microliter, with a linear range spanning almost 4 orders of magnitude. The sensor is specific and readily differentiates exosomes from microvesicles in samples containing 1000-fold excess of the latter. Capability of detecting exosomes in real samples (diluted serum) was shown. This was achieved by immobilizing rabbit antihuman CD9 antibodies on gold substrates and using monoclonal antibodies against CD9 for detection of captured exosomes. Signal amplification is presumably obtained from the fact that multiple detector antibodies bind to the surface of each captured vesicle. Detection is performed based on electrochemical reduction of 3,3',5,5'-tetramethyl benzidine (TMB) after addition of horseradish peroxidase (HRP)-conjugated anti-IgG antibodies. This amperometric biosensor can be easily incorporated into future miniaturized and semiautomatic devices for EV determination.


Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in Behçet's disease: which and when to use?
Behçet's disease (BD) is an uncommon autoimmune/autoinflammatory disease. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were investigated in many diseases as a marker of inflammation. In this study, we investigated NLR and PLR in patients with BD as a marker of disease activity and its association with different clinical manifestations. The study included 23 BD patients; their mean age was (32.5 ± 6.76) and M:F ratio was 16:7. Complete blood picture was done for all patients. NLR and PLR were compared in both active and inactive BD patients and its relation with different clinical manifestations was assessed. NLR was higher in active BD patients than in inactive BD patients (P < 0.01). Although both NLR and PLR were correlated with Behçet's Disease Current Activity Form (BDCAF), the correlation of NLR with BDCAF was much stronger than that of PLR. NLR was associated with some mucocutaneous lesions. Both NLR and PLR were associated with articular and GIT manifestations, but also NLR showed more significant results. In our studied patients, both NLR and PLR were not informative about any ongoing ocular activity (P > 0.05). Both ratios were not affected by the presence of neurologic deficits nor previous vascular events (P > 0.05). NLR was superior to PLR as an indicator of disease activity. NLR was closely related to skin manifestations while PLR was not. In our study, both were not considered reliable in representing ocular activity.


Combined bimolecular fluorescence complementation and Forster resonance energy transfer reveals ternary SNARE complex formation in living plant cells.
Various fluorophore-based microscopic methods, comprising Förster resonance energy transfer (FRET) and bimolecular fluorescence complementation (BiFC), are suitable to study pairwise interactions of proteins in living cells. The analysis of interactions between more than two protein partners using these methods, however, remains difficult. In this study, we report the successful application of combined BiFC-FRET-fluorescence lifetime imaging microscopy and BiFC-FRET-acceptor photobleaching measurements to visualize the formation of ternary soluble N-ethylmaleimide-sensitive factor attachment receptor complexes in leaf epidermal cells. This method expands the repertoire of techniques to study protein-protein interactions in living plant cells by a procedure capable of visualizing simultaneously interactions between three fluorophore-tagged polypeptide partners.


Evaluation of ventilatory efficiency during exercise in patients with idiopathic scoliosis undergoing spinal fusion.
A prospective evaluation of ventilatory function following spinal fusion in adolescent idiopathic scoliosis. To prospectively evaluate pulmonary function, maximal oxygen uptake, and ventilatory efficiency during exercise in patients with adolescent idiopathic scoliosis before surgery and a minimum of 2 years postoperation. For reasons that are unclear, patients with untreated adolescent idiopathic scoliosis tend to avoid aerobic exercise. Their reluctance may be the result of low ventilatory efficiency, as they often approach their ventilatory ceiling at maximum oxygen uptake despite forced vital capacities that are near normal. This inefficiency of ventilation with exercise may explain the reluctance of patients with scoliosis to pursue aerobic fitness. No study has evaluated the effect spinal fusion has on the ventilatory function of patients with scoliosis during exercise. Forty-two patients with adolescent idiopathic scoliosis (36 female and 6 male) at an average age of 14 +/- 3 years (range 10-18 years) underwent spinal fusion. Twenty patients underwent a posterior spinal fusion alone, 20 an anterior spinal fusion alone, and 2 an anterior spinal fusion and posterior spinal fusion. The average Cobb measurement was 55 degrees (range 40-85 degrees). Pulmonary function values (forced vital capacity, total lung capacity, maximum voluntary ventilation), maximum oxygen uptake (VO2max), and ventilatory efficiency were obtained before surgery and a minimum of 2 years postoperation. For all patients, forced vital capacity percent predicted decreased from 88.1% to 81.4% (P < 0.0001). Total lung capacity also declined from 90.5% to 88.5% but was not statistically significant (P = 0.189). Percent predicted maximum oxygen uptake (VO2max) declined from 93.6% to 85.1% (P = 0.00029). Ventilatory efficiency, as measured by VEmax/maximum voluntary ventilation, improved from 0.76 to 0.68 (P = 0.005), whereas measured by VEmax/FEV1 x 40 was unchanged from 0.69 to 0.70 (P = 0.172) postoperation. The choice of operative approach [anterior (n = 20) versus posterior (n = 20)] or whether rib graft was harvested (n = 33) versus iliac crest graft (n = 7) did not change these results. Improvement in ventilatory efficiency during exercise does not occur in the majority of patients with adolescent idiopathic scoliosis following spinal fusion and thus cannot be relied on to foster increases in aerobic activity.


Amine-Linked Covalent Organic Frameworks as a Platform for Postsynthetic Structure Interconversion and Pore-Wall Modification.
Covalent organic frameworks have emerged as a powerful synthetic platform for installing and interconverting dedicated molecular functions on a crystalline polymeric backbone with atomic precision. Here, we present a novel strategy to directly access amine-linked covalent organic frameworks, which serve as a scaffold enabling pore-wall modification and linkage-interconversion by new synthetic methods based on Leuckart-Wallach reduction with formic acid and ammonium formate. Frameworks connected entirely by secondary amine linkages, mixed amine/imine bonds, and partially formylated amine linkages are obtained in a single step from imine-linked frameworks or directly from corresponding linkers in a one-pot crystallization-reduction approach. The new, 2D amine-linked covalent organic frameworks, rPI-3-COF, rTTI-COF, and rPy1P-COF, are obtained with high crystallinity and large surface areas. Secondary amines, installed as reactive sites on the pore wall, enable further postsynthetic functionalization to access tailored covalent organic frameworks, with increased hydrolytic stability, as potential heterogeneous catalysts.


T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blocker Therapy.
Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: (1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; (2) in anti-TNF responders as well as in nonresponders, the frequencies of naïve CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; (3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; (4) pending confirmation, a CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA. The ClinicalTrials.gov registration number of our study is NCT03266822.


Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?
With COVID-19 vaccine roll-out ongoing in many countries globally, monitoring of breakthrough infections is of great importance. Antibodies persist in the blood after a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Since COVID-19 vaccines induce immune response to the Spike protein of the virus, which is the main serosurveillance target to date, alternative targets should be explored to distinguish infection from vaccination. Multiplex immunoassay data from 1,513 SARS-CoV-2 RT-qPCR-tested individuals (352 positive and 1,161 negative) without COVID-19 vaccination history were used to determine the accuracy of Nucleoprotein-specific immunoglobulin G (IgG) in detecting past SARS-CoV-2 infection. We also described Spike S1 and Nucleoprotein-specific IgG responses in 230 COVID-19 vaccinated individuals (Pfizer/BioNTech). The sensitivity of Nucleoprotein seropositivity was 85% (95% confidence interval: 80-90%) for mild COVID-19 in the first two months following symptom onset. Sensitivity was lower in asymptomatic individuals (67%, 50-81%). Participants who had experienced a SARS-CoV-2 infection up to 11 months preceding vaccination, as assessed by Spike S1 seropositivity or RT-qPCR, produced 2.7-fold higher median levels of IgG to Spike S1 ≥ 14 days after the first dose as compared to those unexposed to SARS-CoV-2 at ≥ 7 days after the second dose (p = 0.011). Nucleoprotein-specific IgG concentrations were not affected by vaccination in infection-naïve participants. Serological responses to Nucleoprotein may prove helpful in identifying SARS-CoV-2 infections after vaccination. Furthermore, it can help interpret IgG to Spike S1 after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.


eLearning and Embryology: Designing an Application to Improve 3D Comprehension of Embryological Structures.
Embryology and histology are subjects that are viewed as particularly challenging by students in higher education. This negative perception is the result of many factors such as restricted access to lab facilities, lack of allocated time to these labs, and the complexity of the subject itself. One main factor that influences this viewpoint is the difficulty of grasping 3D orientation of sectioned tissues, especially regarding embryology. Attempts have been made previously to create alternative teaching methods to help alleviate these issues, but few have explored 3D visualisation. We aimed to address these issues by creating 3D embryological reconstructions from serial histology sections of a sheep embryo. These were deployed in a mobile application that allowed the user to explore the original sections in sequence, alongside the counterpart 3D model. The application was tested against a currently available eHistology programme on a cohort of life sciences graduates (n = 14) through qualitative surveys and quantitative testing through labelling and orientation-based tests. The results suggest that using a 3D modality such as the one described here significantly improves student comprehension of orientation of slides compared to current methods (p = 0.042). Furthermore, the developed application was deemed more interesting, useful, and usable than current eHistology tools (p < 0.05). Modalities such as that developed here could therefore provide a more effective approach to learning these challenging subjects potentially increasing student engagement with embryology and histology.


Genetic contributions to plasma total antioxidant activity.
Oxidative stress plays important roles in a wide spectrum of pathological processes, such as atherosclerosis. Although several environmental factors are documented to influence redox metabolism, relatively little is known about genetic effects. In the present study, we evaluated genetic contributions to variation in plasma total antioxidant status (TAS), a measure of peroxyl-scavenging capacity, in 1337 members of 40 Mexican American families. TAS levels were significantly lower in women than in men (1.675+/-0.004 versus 1.805+/-0.005 mmol/L, respectively; P<0.001), and there was a significant decline of TAS levels with age in men but not in women (P<0.01 for the interaction). Quantitative genetic analysis indicated the heritability of TAS levels to be 0.509+/-0.052; ie, approximately 51% of the residual variance (after covariate adjustment) in TAS levels was due to the additive effects of genes (P<0.001). We have further observed a significant gene-by-smoking interaction (P<0.05). Additive genetic effects account for 83% of the residual phenotypic variance in TAS levels among smokers, but they account for only 49% in nonsmokers. However, genes contributing to TAS variation are the same in smokers and nonsmokers. Our study for the first time demonstrates that TAS, an indicator of redox homeostasis, is under strong genetic control, especially among smokers. With appropriate tools, such as genome screening, it should be possible to localize genes that regulate redox homeostasis and, ultimately, identify the DNA sequence variants predisposing subjects to oxidative damage.


Trajectories of discrimination among Chinese American youth: Variation, predictors, and outcomes.
Using 3 waves of longitudinal data from 444 Chinese American adolescents (Mage = 13.04 at Wave 1, 54% identified as women), the current study explored if there was variation in discrimination trajectories from early to late adolescence and whether contextual and individual factors predicted trajectories as well as if trajectories were associated with academic achievement and mental health. Three distinct discrimination trajectories were identified: low-increasing, moderate-stable, and high-decreasing. The results also revealed that neighborhood Chinese concentration and adolescents' acculturation predicted discrimination trajectories. Different trajectories were also associated with depressive symptoms; adolescents in the high-decreasing trajectory reported higher levels of depressive symptoms in late adolescence than in the other two trajectories. The findings highlight the heterogeneity in Chinese American adolescents' discrimination experience.


Association of p59(fyn) with the T lymphocyte costimulatory receptor CD2. Binding of the Fyn Src homology (SH) 3 domain is regulated by the Fyn SH2 domain.
Human CD2 is a 50-55-kDa cell surface receptor specifically expressed on the surface of T lymphocytes and NK cells. Stimulation of human peripheral blood T cells with mitogenic pairs of anti-CD2 monoclonal antibodies (mAbs) is sufficient to induce interleukin-2 production and T cell proliferation in the absence of an antigen-specific signal through the T cell receptor. CD2 has been shown previously to associate physically with the Src family protein-tyrosine kinases p56(lck) and p59(fyn). We now report that stimulation of T cells with mitogenic pairs of anti-CD2 mAbs enhanced the association of the Fyn polypeptide with the CD2 complex, whereas stimulation with single anti-CD2 mAb had minimal effect. Using glutathione S-transferase (GST) fusion proteins, we found that CD2 bound to the Src homology (SH) 3 domain of Fyn. Interestingly, the CD2-Fyn association was negatively regulated by the Fyn SH2 domain; CD2 bound poorly to GST fusion proteins expressing both the SH2 and SH3 domains of Fyn. However, the inhibitory effect of the Fyn SH2 domain on binding of the Fyn SH3 domain to CD2 was relieved by peptides containing a phosphorylated YEEI sequence that bound directly to the Fyn SH2 domain. In addition, we found that the ability of the Fyn SH2 domain to precipitate tyrosine-phosphorylated proteins, including the CD3zeta chain, was enhanced after T cell stimulation with mitogenic pairs of CD2 mAbs. Finally, overexpression of a mutated Fyn molecule, in which the ability of the Fyn SH2 domain to bind phosphotyrosine-containing proteins was abrogated, inhibited CD2-induced transcriptional activation of the nuclear factor of activated T cells (NFAT), suggesting a functional involvement of the Fyn SH2 domain in CD2-induced T cell signaling. We thus propose that stimulation through the CD2 receptor leads to the tyrosine phosphorylation of intracellular proteins, including CD3zeta itself, which in turn bind to the Fyn-SH2 domain, allowing the direct association of the Fyn SH3 domain with CD2 and the initiation of downstream signaling events.


A Cretaceous terrestrial snake with robust hindlimbs and a sacrum.
It has commonly been thought that snakes underwent progressive loss of their limbs by gradual diminution of their use. However, recent developmental and palaeontological discoveries suggest a more complex scenario of limb reduction, still poorly documented in the fossil record. Here we report a fossil snake with a sacrum supporting a pelvic girdle and robust, functional legs outside the ribcage. The new fossil, from the Upper Cretaceous period of Patagonia, fills an important gap in the evolutionary progression towards limblessness because other known fossil snakes with developed hindlimbs, the marine Haasiophis, Pachyrhachis and Eupodophis, lack a sacral region. Phylogenetic analysis shows that the new fossil is the most primitive (basal) snake known and that all other limbed fossil snakes are closer to the more advanced macrostomatan snakes, a group including boas, pythons and colubroids. The new fossil retains several features associated with a subterranean or surface dwelling life that are also present in primitive extant snake lineages, supporting the hypothesis of a terrestrial rather than marine origin of snakes.


Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.
Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus common cold infection. At low doses, COVID-19 cocktails induced glomerular injury and albuminuria in zinc fingers and homeoboxes 2 (Zhx2) hypomorph and Zhx2+/+ mice to mimic COVID-19-related proteinuria. Common Cold cocktail induced albuminuria selectively in Zhx2 hypomorph mice to model relapse of minimal change disease, which improved after depletion of TNF-α, soluble IL-4Rα, or IL-6. The Zhx2 hypomorph state increased cell membrane to nuclear migration of podocyte ZHX proteins in vivo (both cocktails) and lowered phosphorylated STAT6 activation (COVID-19 cocktail) in vitro. At higher doses, COVID-19 cocktails induced acute heart injury, myocarditis, pericarditis, acute liver injury, acute kidney injury, and high mortality in Zhx2+/+ mice, whereas Zhx2 hypomorph mice were relatively protected, due in part to early, asynchronous activation of STAT5 and STAT6 pathways in these organs. Dual depletion of cytokine combinations of TNF-α with IL-2, IL-13, or IL-4 in Zhx2+/+ mice reduced multiorgan injury and eliminated mortality. Using genome sequencing and CRISPR/Cas9, an insertion upstream of ZHX2 was identified as a cause of the human ZHX2 hypomorph state.


[Augmentation of mandibular bone with hydroxylapatite--follow-up].
A group of 31 patients whose mandibles had been augmented surgically with various methods using hydroxylapatite granules between 1984 and 1987, were followed-up to rate their subjective and objective masticatory function. The subjective assessment of the treatment result is comparable to the opinion given about vestibulo- and floor of the mouth-plasty. Masticatory function determined according to the method of fractionated sieving of the chewed food did not show any significant differences from the function measured in complete denture patients with strong alveolar bones. The need for regular follow-up is emphasized.


Interaction Between the Rubidium Cation and [2.2.2]Paracyclophane: Experimental and Theoretical Study.
By means of electrospray ionization mass spectrometry (ESI-MS), it was evidenced experimentally that the rubidium cation (Rb+) reacts with the electroneutral [2.2.2]paracyclophane ligand (C24H24) to form the cationic complex [Rb(C24H24)]+. Moreover, applying quantum chemical calculations, the most probable conformation of the proven [Rb(C24H24)]+ complex was solved. In the complex [Rb(C24H24)]+ having a symmetry very close to C3, the "central" cation Rb+, fully located in the cavity of the parent [2.2.2]paracyclophane ligand, is coordinated to all three benzene rings of [2.2.2]paracyclophane via cation-π interaction. Finally, the binding energy, E(int), of the considered cation-π complex [Rb(C24H24)]+ was evaluated as -99.3 kJ/mol, confirming the formation of this fascinating complex species as well. This means that the [2.2.2]paracyclophane ligand can be considered as a receptor for the rubidium cation in the gas phase.


[Electron transport chain of the Candida mycoderma mutant lacking cytochromes b and a+a3].
Two electrontransport chains--"oxygen" and "peroxidase"--were found to operate in the mutant of Candida mycoderma lacking cytochromes b and a+a3; the terminal acceptors of electrons are oxygen and hydrogen peroxide, respectively. The "oxygen" chain lacks cytochromes but contains pyridine nucleotides and flavoproteins; it is inhibited by rotenone and benzhydroxamic acid. The "peroxidase" chain consists of pyridine nucleotides, cytochrome c, and cytochrome c peroxidase; it is inhibited by cyanide.


Chronic AMP-activated protein kinase activation and a high-fat diet have an additive effect on mitochondria in rat skeletal muscle.
Factors that stimulate mitochondrial biogenesis in skeletal muscle include AMP-activated protein kinase (AMPK), calcium, and circulating free fatty acids (FFAs). Chronic treatment with either 5-aminoimidazole-4-carboxamide riboside (AICAR), a chemical activator of AMPK, or increasing circulating FFAs with a high-fat diet increases mitochondria in rat skeletal muscle. The purpose of this study was to determine whether the combination of chronic chemical activation of AMPK and high-fat feeding would have an additive effect on skeletal muscle mitochondria levels. We treated Wistar male rats with a high-fat diet (HF), AICAR injections (AICAR), or a high-fat diet and AICAR injections (HF + AICAR) for 6 wk. At the end of the treatment period, markers of mitochondrial content were examined in white quadriceps, red quadriceps, and soleus muscles, predominantly composed of unique muscle-fiber types. In white quadriceps, there was a cumulative effect of treatments on long-chain acyl-CoA dehydrogenase, cytochrome c, and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) protein, as well as on citrate synthase and beta-hydroxyacyl-CoA dehydrogenase (beta-HAD) activity. In contrast, no additive effect was noted in the soleus, and in the red quadriceps only beta-HAD activity increased additively. The additive increase of mitochondrial markers observed in the white quadriceps may be explained by a combined effect of two separate mechanisms: high-fat diet-induced posttranscriptional increase in PGC-1alpha protein and AMPK-mediated increase in PGC-1alpha protein via a transcriptional mechanism. These data show that chronic chemical activation of AMPK and a high-fat diet have a muscle type specific additive effect on markers of fatty acid oxidation, the citric acid cycle, the electron transport chain, and transcriptional regulation.


[Rebound tonometry in a clinical setting. Comparison with applanation tonometry].
Rebound tonometry has recently been modified for its use in humans. The purpose of our study was to determine the precision of the ICare(R) rebound tonometer (RBT) as compared with the Goldmann applanation tonometer (GAT). Patients were recruited from our Hospital's Glaucoma Unit. In each patient, intraocular pressure (IOP) was measured without anaesthesia using the RBT and ten minutes later using the GAT. Central corneal thickness (CCT) was measured by pachymetry. Sixty-eight patients were recruited (132 eyes). Mean IOP readings with RBT were 18.9 +/- 7.2 (SD) mmHg and were 15.5 +/- 5.7 mmHg with GAT (p<0.001). There was a good correlation between both instruments (r = 0.87, p<0.001). In most cases (84.6%) the IOP measured with the RBT was greater than that measured with the GAT. The mean difference between both instruments was 3.4 +/- 3.6 mmHg. There was a trend towards greater differences between those obtained using the RBT than the GAT when IOP values were higher. A statistically significant correlation was found between IOP readings with both tonometers and CCT, with higher differences being seen as the CCT increased. The RBT can be employed in a clinical setting taking into account that it usually overestimates IOP as compared with the GAT. It could be especially useful in glaucoma screening campaigns since it can be operated by a trained technician.


Properties of calcium channels in guinea-pig gastric myocytes.
1. The inward membrane current in enzymatically dispersed guinea-pig gastric myocytes was studied using whole-cell voltage clamp technique. 2. Only one inward membrane current was found in gastric myocytes which was identified as the Ca2+ current based on its inhibition by Ni2+, Cd2+ and Co2+, its dependence on [Ca2+]o, and its insensitivity to variations of [Na+]o. 3. Ca2+ current activated at -20 mV, peaked around +10 mV and was markedly enhanced when the holding potential was increased from -40 to -90 mV. The enhancement of ICa at negative holding potentials did not alter the activation threshold of ICa. When Ba2+ was substituted for Ca2+, IBa was similarly enhanced at more negative potentials. 4. In cells where internal Ca2+ was buffered with 10 mM-EGTA, the time course of inactivation was fitted with two exponentials, with time constants: tau f = 53.4 +/- 18.1 ms and tau s = 175.2 +/- 46.1 ms. When Ba2+ was the charge carrier through the channel, the time course of inactivation could be fitted often by only one exponential which approximated tau s for inactivation of ICa. The voltage dependence of steady-state inactivation of Ca2+ channels was not significantly altered when Ba2+ was the charge carrier. 5. Using different buffering systems (EGTA, EDTA and citrate), we found that citrate maintained the ICa and slowed inactivation more effectively than the other buffers tested. Because the calculated change in [Ca2+]i did not differ significantly between buffer systems, we speculate that suppression of inactivation by citrate is related to increased accessability of the buffer to cytoplasmic Ca2+ near the Ca2+ channel. Changes in [Mg2+]i affected peak ICa but not the kinetics of inactivation indicating that [Mg2+]i may regulate the steady-state inactivation or the availability of the Ca2+ channels. 6. The divalent selectivity of the Ca2+ channel had the following sequence: Ba2+ greater than Ca2+ greater than or equal to Sr2+ much greater than Mg2+. In very low extracellular Ca2+ (less than 10(-7) M), the Ca2+ channel conducted Na+. 7. Increasing [H+]o appeared to differentially affect peak and maintained components of ICa. At pH less than 6.5, the maintained component of ICa was suppressed more than the peak component indicating possible time- and voltage-dependent inhibition of ICa by protons. 8. Nifedipine, D600 and diltiazem inhibited ICa in a voltage-dependent manner. The order of potency for inhibition of peak ICa was nifedipine approximately D600 much greater than diltiazem.(ABSTRACT TRUNCATED AT 400 WORDS)


Lateral gene transfer as a support for the tree of life.
Lateral gene transfer (LGT), the acquisition of genes from other species, is a major evolutionary force. However, its success as an adaptive process makes the reconstruction of the history of life an intricate puzzle: If no gene has remained unaffected during the course of life's evolution, how can one rely on molecular markers to reconstruct the relationships among species? Here, we take a completely different look at LGT and its impact for the reconstruction of the history of life. Rather than trying to remove the effect of LGT in phylogenies, and ignoring as a result most of the information of gene histories, we use an explicit phylogenetic model of gene transfer to reconcile gene histories with the tree of species. We studied 16 bacterial and archaeal phyla, representing a dataset of 12,000 gene families distributed in 336 genomes. Our results show that, in most phyla, LGT provides an abundant phylogenetic signal on the pattern of species diversification and that this signal is robust to the choice of gene families under study. We also find that LGT brings an abundant signal on the location of the root of species trees, which has been previously overlooked. Our results quantify the great variety of gene transfer rates among lineages of the tree of life and provide strong support for the "complexity hypothesis," which states that genes whose products participate to macromolecular protein complexes are relatively resistant to transfer.


Blood levels of CD11b+ memory T lymphocytes are selectively upregulated in patients with active rheumatoid arthritis.
The adhesion molecules CD11b (a beta2-integrin component) and CD54 (ICAM-1) on blood leukocytes were studied by flow cytometry in patients with rheumatoid arthritis (RA). The fractions of CD4+ cells co-expressing CD11b were elevated in 16 patients with active RA compared with those in 16 RA patients who improved during therapy and 8 healthy controls: 0.8+/-0.12% (mean+/-SEM) versus 0.3+/-0.06% (p<0.002) and 0.3+/-0.06% (p<0.005), respectively. Increased levels of CD11b+CD45R0+ cells were observed in patients with active RA compared to those with improved RA and controls: 12.6+/-3.9% versus 4.8+/-2.7% (p<0.002) and 6.1+/-1.2% (p<0.003), respectively. Disease activity, determined by C-reactive protein, correlated with the numbers of CD11b+CD45R0+ cells: r=0.62 (p<0.001). Seven patients were followed during induction of remission with methotrexate and glucocorticoids. The numbers of CD11b+CD4+ and CD11b+CD45R0+ cells fell significantly after clinical improvement. The levels of CD11b+CD14+ cells (monocytes) did not differ between the groups. The number of CD11b+CD15+ cells (neutrophils) was elevated in patients with RA irrespective of disease activity. The levels of CD54+ cells were not different between the RA and control groups. We conclude that the increased numbers of CD11b+ memory T cells may arise from exposure to stimuli outside the synovial compartment.


Light reflected from red mulch to ripening strawberries affects aroma, sugar and organic acid concentrations.
Strawberry (Fragaria ananassa) fruit size and flavor are important to both growers and consumers. Plastic mulches are frequently used in raised-bed culture to conserve water, control weeds with less herbicides, keep fruit clean and produce ripe berries earlier in the season. The most commonly used plastic mulch color is black. We hypothesized that changing mulch color to reflect more far-red (FR) and red light (R) and a higher FR/R photon ratio would keep those benefits and improve berry size and flavor by altering phytochrome-mediated regulation of pathways in ripening berries. Size and chemical composition of berries developed in sunlight over a specially formulated red plastic were compared with those that developed over standard black plastic mulch. Berries that ripened over red were about 20% larger, had higher sugar to organic acid ratios and emitted higher concentrations of favorable aroma compounds. We conclude that FR and the FR/R ratio in light reflected from the red mulch on the soil surface acted through the natural phytochrome system within the growing plants to modify gene expression enough to result in increased fruit size and improved concentrations of phytonutrient, flavor and aroma compounds.


Pyrimethamine decreases levels of SOD1 in leukocytes and cerebrospinal fluid of ALS patients: a phase I pilot study.
The mutated SOD1 protein appears to have a gene dose-dependent effect on the severity and progression of ALS. Lowering of SOD1 protein levels might reduce severity and progression of the disease. The antimalarial drug pyrimethamine (PYR) was identified to cause a dose-dependent reduction in SOD1 protein levels in human cells in vitro. To determine if there was a similar effect in humans, we performed a phase I pilot study in 16 ALS patients with SOD1 mutations, 18 weeks in duration. Blood samples were obtained during all visits. The actin normalized leukocyte SOD1 levels were analyzed using Western blot. SOD1 content in the cerebrospinal fluid (CSF) was determined by ELISA and the SOD1 enzymic activity by spectrophotometric analysis using KO2. Clinical assessment of disease severity was assessed using Appel ALS scale and ALSFRS-R. The leukocyte SOD1 levels showed a significant reduction (p > 0.0001) by the third study visit and this reduction was sustained throughout the remainder of the study. CSF also showed a decrease in SOD1 protein content and enzymic activity in the two patients so tested. Thus, PYR use may be associated with a reduction in SOD1 in ALS patients. The significance is uncertain and further detailed study is required.


Trends in Severe Pediatric Emergency Conditions in a National Cohort, 2008 to 2014.
The objective of this study was to determine the incidence and recent trends in serious pediatric emergency conditions. We conducted a cross-sectional study of the Nationwide Emergency Department Sample from 2008 through 2014, and included patients with age below 18 years with a serious condition, defined as each diagnosis group in the diagnosis grouping system with a severity classification system score of 5. We calculated national incidences for each serious condition using annualized weighted condition counts divided by annual United States census child population counts. We determined the highest-incidence serious conditions over the study period and calculated percentage changes between 2008 and 2014 for each serious condition using a Poisson model. The 2008 incidence of serious conditions across the national child population was 1721 visits per million person-years (95% confidence interval, 1485-1957). This incidence increased to 2020 visits per million person-years (95% confidence interval, 1661-2379) in 2014. The most common serious conditions were serious respiratory diseases, septicemia, and serious neurologic diseases. Anaphylaxis was the condition with the largest change, increasing by 147%, from 101 to 249 visits per million person-years. The most common serious condition in children presenting to United States emergency departments is serious respiratory disease. Anaphylaxis is the fastest increasing serious condition. Additional research attention to these diagnoses is warranted.


[Treatment of gastroduodenal ulcer by plasmapheresis and transfusion of thawed-out autologous plasma].
Curative plasmapheresis was performed in 21 patients with duodenal ulcer (DU) and in 3 patients with gastric ulcer (12 DU patients and 3 patients with gastric ulcer were taken as controls). The controls were treated by common pharmaceuticals (except Tagamet). Altogether 117 sessions of plasmapheresis were performed (an average of 5 sessions for each patient 2-3 times a week). Fibrogastroscopy was performed before and after a series of plasmapheresis (2-3 weeks after the start of therapy). In the DU patients treated by plasmapheresis ulcer cicatrization occurred in 18 days, in the controls in 27 days (p less than 0.001). In 3 patients with gastric ulcer treated by plasmapheresis cicatrization occurred on the 24th day, in the controls on the 41st day (p greater than 0.2). This method was proposed for patients with severe conditions due to the fact that a positive effect was also obtained in persons with persistently recurrent ulcers.


Physical activity and incident type 2 diabetes mellitus: a systematic review and dose-response meta-analysis of prospective cohort studies.
Inverse associations between physical activity (PA) and type 2 diabetes mellitus are well known. However, the shape of the dose-response relationship is still uncertain. This review synthesises results from longitudinal studies in general populations and uses non-linear models of the association between PA and incident type 2 diabetes. A systematic literature search identified 28 prospective studies on leisure-time PA (LTPA) or total PA and risk of type 2 diabetes. PA exposures were converted into metabolic equivalent of task (MET) h/week and marginal MET (MMET) h/week, a measure only considering energy expended above resting metabolic rate. Restricted cubic splines were used to model the exposure-disease relationship. Our results suggest an overall non-linear relationship; using the cubic spline model we found a risk reduction of 26% (95% CI 20%, 31%) for type 2 diabetes among those who achieved 11.25 MET h/week (equivalent to 150 min/week of moderate activity) relative to inactive individuals. Achieving twice this amount of PA was associated with a risk reduction of 36% (95% CI 27%, 46%), with further reductions at higher doses (60 MET h/week, risk reduction of 53%). Results for the MMET h/week dose-response curve were similar for moderate intensity PA, but benefits were greater for higher intensity PA and smaller for lower intensity activity. Higher levels of LTPA were associated with substantially lower incidence of type 2 diabetes in the general population. The relationship between LTPA and type 2 diabetes was curvilinear; the greatest relative benefits are achieved at low levels of activity, but additional benefits can be realised at exposures considerably higher than those prescribed by public health recommendations.


Neural induction of taste buds.
Bilateral innervation allows more than 80% of the 610 vallate taste buds to survive removal of one IXth nerve in adult rats. Removal of both IXth nerves in neonatal or adult rats results in the absence of taste buds. In studying development, we found that removing or crushing one IXth nerve in three-day-old neonates profoundly decreased the number of vallate taste buds that subsequently developed. Specifically, after removal of one IXth nerve at 3 days, only 228 taste buds formed, compared with 496 taste buds that one nerve would maintain in adults. Thus, during normal development, the right and left IXth nerves interact synergistically, as at least 150 more taste buds develop than predicted by the sum of the independent action of each IXth nerve. This suggests that vallate taste buds are induced by the IXth nerve. A second example of synergism, representing evidence for the neural induction of taste buds, came from experiments in which we crushed the left IXth nerve 3 days after birth and found that these regenerated IXth nerve axons induced 4 times as many taste buds in the presence of the normal right IXth nerve (118 taste buds) as in its early absence (30 taste buds). We conclude that taste buds are neurally induced and that axons of the IXth nerve interact synergistically in inducing them, rather than competing for targets. We propose that in development innervated progenitor cells form stem cells which lead to taste bud cells.


Heart rate regulation during cycle-ergometer exercise via bio-feedback.
This paper explains our developed control system which regulates the heart rate (HR) to track a desired trajectory. The controller is indeed a non-conventional non-model-based proportional, integral and derivative (PID) controller. The controller commands are interpreted as biofeedback auditory commands. These commands can be heard and implemented by the exercising subject as a part of the control-loop. However, transmitting a feedback signal while the pedals are not in the appropriate position to efficiently exert force may lead to a cognitive disengagement of the user from the feedback controller. This note explains a novel form of control system regarding as "actuator-based event-driven control system", designed specifically for the purpose of this project. We conclude that the developed event-driven controller makes it possible to precisely regulate HR to a predetermined HR profile.


Green clay and aloe vera peel-off facial masks: response surface methodology applied to the formulation design.
This article describes the optimization of a peel-off facial mask formulation. An investigation was carried out on the parameters of the formulation that most affect the desirable characteristics of peel-off facial masks. Cereal alcohol had a significant effect on the drying time at concentrations of 1-12% (w/w). The applicability of the evaluated formulations was influenced by both carbomer (0-2.4%; w/w) and polyvinyl alcohol (PVA; 2.5-17.5%; w/w) content due to their ability to alter the formulation viscosity. Inverse concentrations of carbomer and PVA led to formulations with optimum viscosity for facial application. Film-forming performance was influenced only by the PVA concentration, achieving maximum levels at concentrations of around 11% (w/w). The optimized formulation, determined mathematically, contained 13% (w/w) PVA and 10% (w/w) cereal alcohol with no addition of carbomer. This formulation provided high levels of applicability and film-forming performance, the lowest drying time possible and excellent homogeneity of the green clay particles and aloe vera before and after drying. The preliminary stability study indicated that the optimized formulation is stable under normal storage conditions. The microbiological stability evaluation indicated that the preservative was efficient in terms of avoiding microbial growth. RSM was shown to be a useful statistical tool for the determination of the behavior of different compounds and their concentrations for the responses studied, allowing the investigation of the optimum conditions for the production of green clay and aloe vera peel-off facial masks.


New platinum (II) and palladium (II) complexes of coumarin-thiazole Schiff base with a fluorescent chemosensor properties: Synthesis, spectroscopic characterization, X-ray structure determination, in vitro anticancer activity on various human carcinoma cell lines and computational studies.
A new coumarin-thiazole based Schiff base (Ligand, L) and its Pd(II), Pt(II) complexes; ([Pd(L)2] and [Pt(L)2]), were synthesized and characterized using spectrophotometric techniques (NMR, IR, UV-vis, LC-MS), magnetic moment, and conductivity measurements. A single crystal X-ray analysis for only L was done. The crystals of L have monoclinic crystal system and P21/c space group. To gain insight into the structure of L and its complexes, we used density functional theory (DFT) method to optimize the molecules. The photophysical properties changes were observed after deprotonation of L with CN- via intermolecular charge transfer (ICT). Additionally, as the sensor is a colorimetric and fluorimetric cyanide probe containing active sites such as coumarin-thiazole and imine (CH=N), it showed fast color change from yellow to deep red in the visible region, and yellow fluorescence after CN- addition to the imine bond, in DMSO. The reaction mechanisms of L with CN-, F- and AcO- ions were evaluated using 1H NMR shifts. The results showed that, the reaction of L with CN- ion was due to the deprotonation and addition mechanisms at the same time. The anti-cancer activity of L and its Pd(II) and Pt(II) complexes were evaluated in vitro using MTT assay on the human cancer lines MCF-7 (human breast adenocarcinoma), LS174T (human colon carcinoma), and LNCAP (human prostate adenocarcinoma). The anti-cancer effects of L and its complexes, on human cells, were determined by comparing the half maximal inhibitory concentration (IC50) values. The activity results showed that, the Pd(II) complex of L has higher anti-tumor effect than L and its Pt(II) complex against the tested human breast adenocarcinoma (MCF-7), human prostate adenocarcinoma (LNCAP), and human colon carcinoma (LS174T) cell lines.


Amino Acid transporter inventory of the selaginella genome.
Amino acids play fundamental roles in a multitude of functions including protein synthesis, hormone metabolism, nerve transmission, cell growth, production of metabolic energy, nucleobase synthesis, nitrogen metabolism, and urea biosynthesis. Selaginella as a member of the lycophytes is part of an ancient lineage of vascular plants that had arisen ∼400 million years ago. In angiosperms, which have attracted most of the attention for nutrient transport so far, we have been able to identify many of the key transporters for nitrogen. Their role is not always fully clear, thus an analysis of Selaginella as a representative of an ancient vascular plant may help shed light on the evolution and function of these diverse transporters. Here we annotated and analyzed the genes encoding putative transporters involved in cellular uptake of amino acids present in the Selaginella genome.


Quantitative analyses of T2-weighted MRI as a potential marker for response to somatostatin analogs in newly diagnosed acromegaly.
In growth hormone (GH)-producing adenomas, T2-weighted MRI signal intensity is a marker for granulation pattern and response to somatostatin analogs (SSA). Prediction of treatment response is necessary for individualized treatment, and T2 intensity assessment might improve preoperative classification of somatotropinomas. The objectives of this study are (I) to explore the feasibility of quantitative T2-weighted MRI histogram analyses in newly diagnosed somatotroph adenomas and their relation to clinical and histological parameters and (II) to compare the quantitative method to conventional, visual assessment of T2 intensity. The study was a retrospective cohort study of 58 newly diagnosed patients. In 34 of these, response to primary SSA treatment after median 6 months was evaluated. Parameters from the T2 histogram analyses (T2 intensity ratio and T2 homogeneity ratio) were correlated to visually assessed T2 intensity (hypo-, iso-, hyperintense), baseline characteristics, response to SSA treatment, and histological granulation pattern (anti-Cam5.2). T2 intensity ratio was lowest in the hypointense tumors and highest in the hyperintense tumors (0.66 ± 0.10 vs. 1.07 ± 0.11; p < 0.001). T2 intensity at baseline correlated with reduction in GH (r = -0.67; p < 0.001) and IGF-1 (r = -0.36; p = 0.037) after primary SSA treatment (n = 34). The T2 homogeneity ratio correlated with adenoma size reduction (r = -0.45; p = 0.008). Sparsely granulated adenomas had a higher T2 intensity than densely or intermediately granulated adenomas. T2 histogram analyses are an applicable tool to assess T2 intensity in somatotroph adenomas. Quantitatively assessed T2 intensity ratio in GH-producing adenomas correlates with conventional assessment of T2 intensity, baseline characteristics, response to SSA treatment, and histological granulation pattern.


Evaluating the 2010 New York State HIV testing law in NYC ambulatory practices using electronic health records.
In 2010, the New York State Legislature made it mandatory to offer an HIV test to people aged 13-64 years receiving hospital or primary care services, with limited exceptions. In this study, we used data from New York City practices to evaluate the impact of the law on HIV testing rates in ambulatory care. We collected quarterly testing data from the electronic health records of 218 practices. We calculated overall and stratified crude testing rates. Using univariate and multivariate generalized estimating equation models, we assessed the odds of testing in the year before the law (baseline) versus the first and second year after the law's implementation (year 1 and year 2). During baseline, the odds of testing did not increase significantly. During year 1, the odds of testing significantly increased by 50% in the univariate model and 200% after adjusting for confounders. During year 2, the odds of testing increased 10%. This was only significant in the univariate model. The crude quarterly testing rate increased from 2.8% to 5.7% from baseline to year 2. Our evaluation showed that after the implementation of the HIV testing law, there was an increase in HIV testing among NYC ambulatory practices. Testing rates remained modest, but considerable improvement was seen in community health centers, in age ranges targeted by the law and in practices that were screening for HIV at baseline. This study suggests that legislation may be effective when used in a comprehensive prevention strategy.


Primary human T lymphocytes engineered with a codon-optimized IL-15 gene resist cytokine withdrawal-induced apoptosis and persist long-term in the absence of exogenous cytokine.
IL-15 is a common gamma-chain cytokine that has been shown to be more active than IL-2 in several murine cancer immunotherapy models. Although T lymphocytes do not produce IL-15, murine lymphocytes carrying an IL-15 transgene demonstrated superior antitumor activity in the immunotherapy of B16 melanoma. Thus, we sought to investigate the biological impact of constitutive IL-15 expression by human lymphocytes. In this report we describe the generation of a retroviral vector encoding a codon-optimized IL-15 gene. Alternate codon usage significantly enhanced the translational efficiency of this tightly regulated gene in retroviral vector-transduced cells. Activated human CD4+ and CD8+ human lymphocytes expressed IL-15Ralpha and produced high levels of cytokine upon retroviral transduction with the IL-15 vector. IL-15-transduced lymphocytes remained viable for up to 180 days in the absence of exogenous cytokine. IL-15 vector-transduced T cells showed continued proliferation after cytokine withdrawal and resistance to apoptosis while retaining specific Ag recognition. In the setting of adoptive cell transfer, IL-15-transduced lymphocytes may prolong lymphocyte survival in vivo and could potentially enhance antitumor activity.


Ordered nanopore arrays with large interpore distances via one-step anodization.
Preparation of pre-patterned alumina substrates using bottom-up techniques compatible with nanotechnology applications is still a challenge. We present a novel methodology to achieve superior order in 'anodic' alumina with large interpore distances by a convenient one-step anodization process. The use of transparent insulators renders such anodic layers applicable as templates for nanostructured photovoltaic or photoelectrochemical devices.


Antidyslipidemic Capacity of Cleome arabica (L.) in Streptozotocin-Induced Diabetic Rats.
The aim of the study was to assess the effect of Cleome arabica on lipid metabolism. Cleome arabica (L.) is a medicinal plant used traditionally by the population of North Africa for managing diabetes mellitus. This study was designed to evaluate the antidyslipidemic and antiatherogenic capacities of Cleome arabica (L.) in normal and streptozotocin(STZ)-induced diabetic rats. The hypolipidemic, antihyperglycemic and antiatherogenic effects of oral administration of the aqueous extract of Cleome arabica (CAAE) (100 mg/kg) were evaluated in normal and diabetic rats. In addition, the quantification of polyphenols, flavonoids and tannins as well as the antioxidant activity were performed. The results showed that the extract (CAAE) revealed an antidyslipidemic action by attenuating plasma levels of Total Cholesterol (TC), Triglycerides (TGs), Low-Density Lipoprotein cholesterol (LDL-c), Very low-density lipoprotein cholesterol (VLDL-c) and glucose. Additionally, CAAE exhibited a potent antiatherogenic activity by reducing Atherogenic Coefficient (AC), Castelli's Risk index-I (cri-I), and Castelli's Risk Index-II (CRI-II). Furthermore, the findings indicated that CAAE is abundant with polyphenols, flavonoids and tannins, and exhibited an important antioxidant capacity. The study demonstrates that aqueous Cleome arabica extract was able to ameliorate lipid abnormalities associated with diabetes mellitus. This pharmacological activity might be due to the antioxidant capacities of phytochemical compounds.


Canine eyelid granular cell tumor: a report of eight cases.
To describe a previously unreported neoplasm of the medial canthus and eyelid in dogs. Clinical and pathologic features of granular cell tumors in the dog were reviewed. Granular cell tumors, arising from the medial canthal eyelid of eight dogs, were identified from the archives of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW). The affected dogs ranged in age from 5 to 12 years (mean of 9.25 years). Follow-up information was available for seven of the eight cases. The clinical presentation included swollen hyperemic lids (4/8), ulcerated skin overlying the mass (2/8), and red conjunctiva (7/8). All eight of the cases had firm masses extending from the palpebral conjunctiva to the eyelid margin at the medial canthus. Histologically, the tissue was composed of a highly collagenous neoplastic growth. The neoplastic cells were oval to strap-like cells with an oval bland appearing nucleus and abundant amounts of granular cytoplasm with very distinct cell boundaries. These granular cells were embedded in a dense collagen matrix. A PAS stain faintly highlighted the granular appearance of the neoplastic cells, which is a defining characteristic of this tumor. There was no recurrence in the seven cases available for follow-up. Canine granular cell tumors of the medial canthus present clinically and histologically as a benign neoplasm. Granular cell tumors have a characteristic histological appearance. Granular cell tumors should be on the differential list for nodules of the medial canthus in dogs.


Inactivating effects of the lactoperoxidase system on bacterial lyases involved in oral malodour production.
The main components of oral malodour have been identified as volatile sulfur compounds (VSCs), including hydrogen sulfide (H(2)S) and methyl mercaptan (CH(3)SH). The lactoperoxidase (LPO) system (consisting of LPO, glucose oxidase, glucose and thiocyanate) was previously shown to exhibit antimicrobial activities against some oral bacteria in vitro and suppressive effects on VSCs in mouth air in a clinical trial. Here, we examined the in vitro effects of the LPO system on the activities of the bacterial lyases involved in the production of VSCs by oral anaerobes. The exposure of crude bacterial extracts of Fusobacterium nucleatum and Porphyromonas gingivalis or purified methionine γ-lyase to the LPO system resulted in the inactivation of their lyase activities through l-cysteine and l-methionine, which was linked to the production of H(2)S and CH(3)SH, respectively. The exposure of living F. nucleatum and P. gingivalis cells to the LPO system resulted in the suppression of cell numbers and lyase activities. The inactivation of the crude bacterial extracts of F. nucleatum and purified methionine γ-lyase by the LPO system was partly recovered by the addition of DTT. Therefore, the LPO system may inactivate bacterial lyases including methionine γ-lyase by reacting with the free cysteine residues of lyases. These results suggested that the LPO system suppresses the production of VSCs not only through its antimicrobial effects, but also by its inactivating effects on the bacterial lyases of F. nucleatum and P. gingivalis.


Peripheral arterial disease screening for hemodialysis patients using a fractional-order integrator and transition probability decision-making model.
Atherosclerosis and resultant peripheral arterial disease (PAD) are common complications in patients with type 2 diabetes mellitus or end-stage renal disease and in elderly patients. The prevalence of PAD is higher in patients receiving haemodialysis therapy. For early assessment of arterial occlusion using bilateral photoplethysmography (PPG), such as changes in pulse transit time and pulse shape, bilateral timing differences could be used to identify the risk level of PAD. Hence, the authors propose a discrete fractional-order integrator to calculate the bilateral area under the systolic peak (AUSP). These indices indicated the differences in both rise-timing and amplitudes of PPG signals. The dexter and sinister AUSP ratios were preliminarily used to separate the normal condition from low/high risk of PAD. Then, transition probability-based decision-making model was employed to evaluate the risk levels. The joint probability could be specified as a critical threshold, < 0.81, to identify the true positive for screening low or high risk level of PAD, referring to the patients' health records. In contrast to the bilateral timing differences and traditional methods, the proposed model showed better efficiency in PAD assessments and provided a promising strategy to be implemented in an embedded system.


Spatio-energetic cross talk in photon counting detectors: Detector model and correlated Poisson data generator.
An x-ray photon interacts with photon counting detectors (PCDs) and generates an electron charge cloud or multiple clouds. The clouds (thus, the photon energy) may be split between two adjacent PCD pixels when the interaction occurs near pixel boundaries, producing a count at both of the pixels. This is called double-counting with charge sharing. (A photoelectric effect with K-shell fluorescence x-ray emission would result in double-counting as well). As a result, PCD data are spatially and energetically correlated, although the output of individual PCD pixels is Poisson distributed. Major problems include the lack of a detector noise model for the spatio-energetic cross talk and lack of a computationally efficient simulation tool for generating correlated Poisson data. A Monte Carlo (MC) simulation can accurately simulate these phenomena and produce noisy data; however, it is not computationally efficient. In this study, the authors developed a new detector model and implemented it in an efficient software simulator that uses a Poisson random number generator to produce correlated noisy integer counts. The detector model takes the following effects into account: (1) detection efficiency; (2) incomplete charge collection and ballistic effect; (3) interaction with PCDs via photoelectric effect (with or without K-shell fluorescence x-ray emission, which may escape from the PCDs or be reabsorbed); and (4) electronic noise. The correlation was modeled by using these two simplifying assumptions: energy conservation and mutual exclusiveness. The mutual exclusiveness is that no more than two pixels measure energy from one photon. The effect of model parameters has been studied and results were compared with MC simulations. The agreement, with respect to the spectrum, was evaluated using the reduced χ2 statistics or a weighted sum of squared errors, χred2(≥1), where χred2=1 indicates a perfect fit. The model produced spectra with flat field irradiation that qualitatively agree with previous studies. The spectra generated with different model and geometry parameters allowed for understanding the effect of the parameters on the spectrum and the correlation of data. The agreement between the model and MC data was very strong. The mean spectra with 90 keV and 140 kVp agreed exceptionally well: χred2 values were 1.049 with 90 keV data and 1.007 with 140 kVp data. The degrees of cross talk (in terms of the relative increase from single pixel irradiation to flat field irradiation) were 22% with 90 keV and 19% with 140 kVp for MC simulations, while they were 21% and 17%, respectively, for the model. The covariance was in strong agreement qualitatively, although it was overestimated. The noisy data generation was very efficient, taking less than a CPU minute as opposed to CPU hours for MC simulators. The authors have developed a novel, computationally efficient PCD model that takes into account double-counting and resulting spatio-energetic correlation between PCD pixels. The MC simulation validated the accuracy.


Clinical presentation and predictors of outcome in patients with severe acute exacerbation of chronic obstructive pulmonary disease requiring admission to intensive care unit.
Severe acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) is a common reason for emergency room (ER) visit about which little has been documented from India. Prospective study of the clinical presentation and predictors of outcome in 116 patients presenting with severe AE-COPD requiring admission to the medical intensive care unit between January 2000 and December 2004. Their mean age was 62.1 +/- 9.8 years. There were 102 males. Mean duration of COPD was 7.2 +/- 5.8 years. All males were smokers (22.3 +/- 11.2 pack years); 35.2% smoked cigarettes and 64.8% smoked bidis. All women were exposed to domestic fuel. Associated co-morbid illnesses were present in 81 patients (69.8%); 53(45.7%) had one co-morbid illness and the remaining 28 (54.3%) had two or more co-morbid illnesses. Evidence of past pulmonary tuberculosis (PTB) was present in 28.4% patients; 5 patients who also had type II diabetes mellitus had active PTB. Arterial blood gas analysis revealed respiratory failure in 40 (33.8%) patients (type I 17.5% and type II 82.5%). Invasive mechanical ventilation was required in 18 patients. Sixteen (13.7%) patients died. Stepwise multivariate logistic regression analysis revealed need for invasive ventilation (OR 45.809, 95% CI 607.46 to 3.009;p < 0.001); presence of co-morbid illness (OR 0.126, 95% CI 0.428 to 0.037;p < 0.01) and hypercapnia (OR 0.114, 95% CI 1.324 to 0.010;p < 0.05) were predictors of death. Co-morbid conditions and metabolic abnormalities render the diagnosis of AE-COPD difficult and also contribute to mortality. High prevalence of past PTB and active PTB in patients with AE-COPD suggests an intriguing relationship between smoking, PTB and COPD which merits further study.


Expression and possible roles of extracellular signal-related kinases 1-2 (ERK1-2) in mouse primordial germ cell development.
In the present work, we described the expression and activity of extracellular signal-related kinases 1-2 (ERK1-2) in mouse primordial germ cells (PGCs) from 8.5-14.5 days post coitum (dpc) and investigated whether these kinases play a role in regulating the various processes of PGC development. Using immunofluorescence and immunoblotting to detect the active phosphorylated form of ERK1-2 (p-ERK1-2), we found that the kinases were present in most proliferating 8.5-10.5 dpc PGCs, low in 11.5 dpc PGCs, and progressively increasing between 12.5-14.5 dpc both in female and male PGCs. In vitro culture experiments showed that inhibiting activation of ERK1-2 with the MEK-specific inhibitor U0126 significantly reduced the growth of 8.5 dpc PGCs in culture but had little effect on 11.5-12.5 dpc PGCs. Moreover, we found that the inhibitor did not affect the adhesion of 11.5 dpc PGCs, but it significantly reduced their motility features onto a cell monolayer. Further, while the ability of female PGCs to begin meiosis was not significantly affected by U0126, their progression through meiotic prophase I was slowed down. Notably, the activity of ERK1-2 was necessary for maintaining the correct expression of oocyte-specific genes crucial for germ cells survival and the formation of primordial follicles.


The effectiveness of iron education through a mobile application on donor return after deferral for low hemoglobin.
Low hemoglobin level is a common cause of donor deferral and results in a huge loss of the donor pool. This study aimed to evaluate the effectiveness of a mobile application as an educational tool to enhance donor return and improve hemoglobin levels after deferral. This was an interventional study involving 382 blood donors who were deferred for low hemoglobin. The donors were divided equally into two groups: a control group and the intervention group. The control group received standard management for low hemoglobin deferral, which includes a short counseling session and a 1-month course of oral iron therapy. The intervention group used a mobile application in addition to standard management. The primary endpoint was the number of blood donors who returned during the 7 months of follow-up. The secondary endpoints were the hemoglobin increment at the first visit after the donors' deferral. The return rate was higher in the intervention group, with 81.2% of the donors returning in the 7 months of follow-up compared to 66% of the control group (p<0.001). Male and female donors had mean hemoglobin increments of 1.0 g/dL and 0.7 g/dL, respectively, in the intervention group, compared to decrements of 0.2 g/dL and 0.4 g/dL, respectively, in the control group (p<0.001). Multivariable analysis showed a significant association between intervention method, education level and donation status on donor return (p=0.015, p<0.001, and p<0.001, respectively). Higher return rate and greater hemoglobin increase in the interventional group could be attributed to features in the mobile application. Repeat donors had the highest odds of returning to donate, followed by those with a tertiary level of education, and those given the mobile application. This study showed that a mobile application was effective in enhancing donor return and increasing hemoglobin level among deferred blood donors on their first return.


The relation between quantum and classical field theory with a classical source.
Classical field theory is about fields and how they behave in space-time. Quantum field theory, in practice, usually seems to be about particles and how they scatter. Nevertheless, classical fields must emerge from quantum field theory in appropriate limits, and Michael Duff showed how this happens for the Schwarzschild solution in perturbative quantum gravity. In a series of papers, we and others have shown how classical radiation from an accelerated charge emerges from quantum field theory when the Unruh thermal effect is taken into account. Here, we sharpen those conclusions by showing that, even at finite times, the quantum picture is meaningful and is in close agreement with the classical picture.


A Rapid, Sensitive, Low-Cost Assay for Detecting Hydrogenotrophic Methanogens in Anaerobic Digesters Using Loop-Mediated Isothermal Amplification.
Understanding how the presence, absence, and abundance of different microbial genera supply specific metabolic functions for anaerobic digestion (AD) and how these impact on gas production is critical for a long-term understanding and optimization of the AD process. The strictly anaerobic methanogenic archaea are essential for methane production within AD microbial communities. Methanogens are a phylogenetically diverse group that can be classified into three metabolically distinct lineages based on the substrates they use to produce methane. While process optimization based on physicochemical parameters is well established in AD, measurements that could allow manipulation of the underlying microbial community are seldom used as they tend to be non-specific, expensive, or time-consuming, or a combination of all three. Loop-mediated isothermal amplification (LAMP) assays combine a simple, rapid, low-cost detection technique with high sensitivity and specificity. Here, we describe the optimization of LAMP assays for the detection of four different genera of hydrogenotrophic methanogens: Methanoculleus, Methanothermobacter, Methanococcus, and Methanobrevibacter spp. By targeting archaeal elongation factor 2 (aEF2), these LAMP assays provide a rapid, low-cost, presence/absence indication of hydrogenotrophic methanogens that could be used as a real-time measure of process conditions. The assays were shown to be sensitive to 1 pg of DNA from most tested methanogen species, providing a route to a quantitative measure through simple serial dilution of samples. The LAMP assays described here offer a simple, fast, and affordable method for the specific detection of four different genera of hydrogenotrophic methanogens. Our results indicate that this approach could be developed into a quantitative measure that could provide rapid, low-cost insight into the functioning and optimization of AD and related systems.


Clinical and economic impact of implementing a comprehensive diabetes management program in managed care.
Diabetes mellitus places a significant burden on the U.S. healthcare system. Because of the potential to reduce diabetic complications and costs through intensive management, diabetes has become a primary target for disease management programs. We performed a retrospective analysis of short-term baseline and follow-up clinical, economic, and member and provider satisfaction data from approximately 7,000 people with diabetes being treated through seven managed care plans using Diabetes Treatment Centers of America's Diabetes NetCare, (Nashville, TN), a comprehensive diabetes management program. Our analysis indicates that Diabetes NetCare achieved gross economic adjusted savings of $50 per diabetic member per month (12.3%), with gross unadjusted savings of $44 (10.9%) per diabetic member per month. Hospital admissions per 1,000 diabetic member years decreased by 18%, and bed days fell by 21%. Patients with diabetes were more likely to get HbAlc tests, foot exams, eye exams, and cholesterol screenings while enrolled in the program. These data suggest that implementation of a comprehensive healthcare management program for people with diabetes can lead to substantial improvements in costs and clinical outcomes in the short-term. It is expected that improvements will increase over time, with continuing improvements in health status and a reduction in the number of future diabetic complications.


Toxicological effects of prolonged and intense use of mosquito coil emission in rats and its implications on malaria control.
Mosquito coil is a vector control option used to prevent malaria in low income counties, while some studies have addressed this issue, additional reseach is required to increase knowledge on the adverse health effects caused by the prolonged use of coils. In this study we investigated the toxicological effects of fumes from two locally manufactured mosquito coil insecticides (with pyrethroids: transfluthrin and d-allethrin as active ingredients) on male albino rats. For this, we recorded the haematological and biochemical indices, and made histopathology and mutagenicity evaluations in rats exposed to mosquito fumes during 2, 4, 8, 12 and 16 week periods. Haematological determination was performed using automated hematology analyzer to determine White Blood Cell (WBC), Packed Cell Volume (PCV), Red Blood Cell (RBC) and Platelet (PLT) counts, while biochemical evaluations were determined using available commercial kits. Gross histopathological changes were studied for the kidney, liver and lungs in sacrificed rats. The rat sperm head abnormalities assessment was used to evaluate mutagenicity. Mosquito coil fumes produced significant increase (P < 0.05) in the levels of total protein, total albumin and bilirubin, when animals were exposed from two weeks to 16 weeks with transfluthrin. Similarly, elevation in the activities of aspartate amino transferase, alanine amino transferase and alanine phosphatase, increased significantly in both insecticides. Increase in WBC, RBC and PCV were recorded for all the exposure periods, however PLT count showed no significant increase (P > 0.05). Mutagenicity assessment revealed sperm abnormality was statistically significant (P < 0.05) compared with the control at 8, 12 and 16 weeks post exposure to transfluthrin. Histological studies revealed severe lung damage evidenced by interstitial accumulations, pulmonary oedema and emphysema in exposed rats. Intracellular accumulations and severe sinusoidal congestion of liver cells were observed from 12 weeks exposure, indicating liver damage. Our studies indicate that mosquito coil fumes do initiate gradual damage to the host. These pathological effects must be taken into consideration by the malaria control program, particularly when regulating their long term and indoor usage.


Parameters of quality assurance: an evolving science.
The quality assurance field is rapidly evolving. The components of the quality assurance field, which include philosophy, assessment tools and methods, analysis and application of data, and research, are each growing in their conceptual validity and are also developing well defined relationships to each other. The philosophy underlying quality assurance has moved from a static concept of quality to conceptualising the quality of care as a dynamic state of health care. Quality assessment tools and methods are more valid and reliable, and research is emphasising outcomes of care and effectiveness studies, as well as methods of disseminating information to practitioners. This paper provides an overview of the quality assurance field, describing the changes that are taking place in each of its components and the relationships among them.


Resting energy expenditure and substrate oxidation rates in cystic fibrosis.
The resting energy expenditure (REE) and substrate oxidation rates in 16 patients with cystic fibrosis who had mild chest disease and 11 healthy controls were measured using indirect calorimetry. The mean REE (% predicted) in the patients with cystic fibrosis was 11% greater than in the controls. Five patients with cystic fibrosis were hypermetabolic but only one of these had a clinically significant reduction of respiratory function. A greater proportion of REE was derived from carbohydrate oxidation in the cystic fibrosis patients (43.5% v 29.9%). However, the 24 hour dietary intake of carbohydrate was greater in the cystic fibrosis group (49.6 v 45.8% of energy intake). These data suggest that a high dietary intake of carbohydrate may contribute to the increased oxidation of carbohydrate in these cystic fibrosis patients. All patients with cystic fibrosis, including those with apparently mild lung disease, should continue to receive a high energy diet.


Treatment and treatment trials in multiple sclerosis.
This review focuses on advances in current and novel treatment approaches in multiple sclerosis. New therapeutic approaches in multiple sclerosis are emerging. Orally available treatment strategies are more acceptable for patients and may improve adherence to therapy. An oral formulation of glatiramer acetate failed to demonstrate efficacy in a clinical trial, but other promising compounds are on the horizon, such as FTY720. Advances are currently being made in use of therapeutic monoclonal antibodies that specifically target key molecules involved in the immunopathogenesis of multiple sclerosis. Natalizumab directed against the adhesion molecule very late antigen-4 represents the first specific antibody to be added to our therapeutic armamentarium for multiple sclerosis. Further evidence that immunomodulation should be initiated as early as possible has been reported. Treatment of multiple sclerosis has changed dramatically over the past decade. Enhanced understanding of the immunopathological processes that underlie the disease, advances in biotechnology and development of powerful magnetic resonance imaging technologies, together with improvements in clinical trial design have led to a variety of valuable therapeutic approaches, which are currently being studied in detail.


Cross-linking of human FcgammaRIIIb induces the production of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor by polymorphonuclear neutrophils.
We have reported that human autoantibodies reacting with the polymorphonuclear neutrophil (PMN)-anchored FcgammaRIIIb (CD16) protect these cells from spontaneous apoptosis. In this study, we used anti-CD16 F(ab')(2) to delineate the mechanism(s) whereby the PMN life span is extended. As documented using four methods, CD16 cross-linking impeded spontaneous apoptosis, whereas anti-CD18 F(ab')(2) exerted no effect. Incubation of PMNs with anti-CD16 prevented the up-regulation of beta(2) integrins, particularly CD11b, which is the alpha-chain of complement receptor type 3, but also CD18, which is its beta-chain, as well as CD11a and CD11c. Anti-CD16-conditioned supernatant of PMNs diminished the percentage of annexin V-binding fresh PMNs after another 18 h in culture, whereas the negative control anti-CD18 had no effect. The expression of mRNA for G-CSF and GM-CSF was induced by anti-CD16, followed by the release of G-CSF and GM-CSF in a dose-dependent manner. Anti-G-CSF and anti-GM-CSF mAbs abrogated the antiapoptotic effect of the related growth factors. The delay in apoptosis was accompanied by a down-regulated expression of Bax, and a partial reduction of caspase-3 activity. These data suggest an autocrine involvement of anti-CD16-induced survival factors in the rescue of PMNs from spontaneous apoptosis. Thus, apoptosis of aged PMNs can be modulated by signaling through FcgammaRIIIb, which may occur in patients with PMN-binding anti-FcgammaRIIIb autoantibodies.


Underutilization of echocardiography for patent foramen ovale in divers with serious decompression sickness.
The presence of a patent foramen ovale (PFO) in compressed gas diving has been considered a risk factor for serious decompression illness (DCS) for more than 20 years. We conducted a ten year retrospective chart review aimed at determining if physicians treating DCS in a university medical center setting used echocardiography to assess PFO in patients with severe DCS, and if so whether PFO is over-represented in that population. Over the ten-year period, 113 divers underwent recompression therapy for decompression sickness. Of these patients, 48 had serious DCS defined by at least one objective neurological finding. We reviewed medical records for the presence of agitated saline contrast echocardiogram testing and whether or not PFO was present. Only 12 of 48 patients with serious DCS underwent transthoracic agitated saline contrast echocardiogram testing. Of these 12 patients, 6 (50%) had a resting PFO. Binomial proportion testing yielded 95% confidence limits of 21% and 79%. Given 27% PFO prevalence in the general population, PFO may be over-represented in our group of most seriously injured DCS patients yet 75% of patients with objective neurological signs did not undergo echocardiography.


Environmental health impacts of tobacco farming: a review of the literature.
To review the literature on environmental health impacts of tobacco farming and to summarise the findings and research gaps in this field. A standard literature search was performed using multiple electronic databases for identification of peer-reviewed articles. The internet and organisational databases were also used to find other types of documents (eg, books and reports). The reference lists of identified relevant documents were reviewed to find additional sources. The selected studies documented many negative environmental impacts of tobacco production at the local level, often linking them with associated social and health problems. The common agricultural practices related to tobacco farming, especially in low-income and middle-income countries, lead to deforestation and soil degradation. Agrochemical pollution and deforestation in turn lead to ecological disruptions that cause a loss of ecosystem services, including land resources, biodiversity and food sources, which negatively impact human health. Multinational tobacco companies' policies and practices contribute to environmental problems related to tobacco leaf production. Development and implementation of interventions against the negative environmental impacts of tobacco production worldwide are necessary to protect the health of farmers, particularly in low-income and middle-income countries. Transitioning these farmers out of tobacco production is ultimately the resolution to this environmental health problem. In order to inform policy, however, further research is needed to better quantify the health impacts of tobacco farming and evaluate the potential alternative livelihoods that may be possible for tobacco farmers globally.


Bone mineral density in familial Mediterranean fever.
The aim of this study was to evaluate the bone mineral density (BMD) in familial Mediterranean fever (FMF) and to search the effects of genetic factors, family history of FMF and types of clinical attacks on BMD. Forty-four attack-free patients with FMF and 36 healthy voluntary subjects were included in the study. BMD measurements of lumbar spine and left proximal femur were performed by dual energy X-ray absorptiometry (DEXA). There was no statistically significant difference between patient and control groups regarding median values of lumbar BMD (P = 0.06), lumbar T (P = 0.08) and Z (P = 0.12) scores, femoral neck BMD (P = 0.13), femoral T (P = 0.22) and Z (P = 0.16) scores and total femur BMD (P = 0.14), T (P = 0.19) and Z (P = 0.27) scores. Patients with negative FMF family history had significantly lower femoral neck BMD (P = 0.018), femoral neck T (P = 0.009) and Z (P = 0.01) scores and total femur BMD (P = 0.033) than patients with positive FMF family history. There was no significant difference among the groups regarding mutation characteristic and types of attacks in lumbar BMD, T and Z scores, femoral neck BMD, T and Z scores and total femur BMD, T and Z scores (P > 0.05). We found that the bone loss of patients with FMF is not different from that of the controls. The increased bone loss in the patients with negative family history for FMF should be further investigated with larger patient groups taking into consideration of the risk factors related to family history for osteoporosis.


Different expression and localization of aquaporin 7 and aquaporin 9 in granulosa cells, oocytes, and embryos of patients with polycystic ovary syndrome and the negatively correlated relationship with insulin regulation.
To investigate the expression of aquaporin 7 (AQP7) and aquaporin 9 (AQP9) in the granulosa cells of patients with polycystic ovary syndrome (PCOS) and healthy women and detect their localization in oocytes at the germinal vesicle (GV), metaphase I (MI), MII, embryo, and blastocyst stages and the in vitro response to insulin stimulation. Randomized, assessor-blinded study. Reproductive medical center. A total of 40 women (aged 20-38 years) comprising 29 cases of primary infertility and 11 cases of secondary infertility, of whom 17 had an initial diagnosis of PCOS and three received a PCOS diagnosis after an infertility examination. Controlling different concentrations of insulin and different treatment times in cultures of normal human granulosa cells in vitro. Expression of AQP7 and AQP9 genes and proteins in granulosa cells detected by real-time quantitative polymerase chain reaction, and localization in oocytes at the GV, MI, MII, embryo, and blastocyst stages by Western blot, immunohistochemical, and immunofluorescence assays, and concentrations of insulin in follicular fluid by enzyme-linked immunosorbent assay. The expression levels of the AQP7 mRNA and protein in the granulosa cells of patients with PCOS were higher than found in healthy controls. We found AQP7 protein expressed in human oocytes at GV, MI, MII, embryo, and blastocyst stages; it was mainly located in the nucleoplasm. In the PCOS group, the expression level of AQP9 mRNA and protein in granulosa cells was lower, and AQP9 protein was expressed in oocytes at the GV, MI, MII, embryo, and blastocyst stages; it was localized on the nuclear membrane. Compared with healthy women, the insulin expression in patients with PCOS was higher. In cultures of normal human granulosa cells in vitro, the expression of AQP7 and AQP9 mRNA and protein decreased with the increase in insulin concentration; expression statistically significantly decreased when the insulin concentration was 100 nmol/L, and after 6 to 24 hours of exposure the lowest expression levels were found at 12 hours. The different localization and expression of AQP7 and AQP9 between the two groups suggests that they might be involved in oocyte maturation and embryonic development through different regulatory pathways. The expression levels of AQP7 and AQP9 were negatively correlated with insulin regulation, suggesting that insulin might affect the maturation of PCOS follicles by changing AQP7 and AQP9 expression.


Evaluation of equine coronavirus fecal shedding among hospitalized horses.
Currently, diagnosis of equine coronavirus (ECoV) relies on the exclusion of other infectious causes of enteric disease along with molecular detection of ECoV in feces or tissue. Although this approach is complete, it is costly and may not always be achievable. We hypothesized that the overall fecal shedding of ECoV in hospitalized horses is low. Our objective was to determine whether systemically healthy horses and horses with gastrointestinal disorders shed ECoV in their feces at the time of admission to a referral hospital and after 48 hours of stress associated with hospitalization. One-hundred thirty adult horses admitted to the Washington State University Veterinary Teaching Hospital for gastrointestinal disease (n = 65) or for imaging under anesthesia (n = 65) that were hospitalized for 48 hours. Owner consent was obtained before sampling. Fecal samples were collected at admission and 48 hours later. Polymerase chain reaction (PCR) for ECoV and electron microscopy (EM) were performed on all samples. Only 1 of 258 fecal samples was PCR-positive for ECoV. Electron microscopy identified ECoV-like particles in 9 of 258 samples, parvovirus-like particles in 4 of 258 samples, and rotavirus-like particles in 1 of 258 samples. The presence of ECoV in feces of hospitalized adult horses was low. Thus, fecal samples that are PCR-positive for ECoV in adult horses that have clinical signs consistent with this viral infection are likely to be of diagnostic relevance. The clinical relevance of the viruses observed using EM remains to be investigated.


Physical mapping of the human and mouse MOG gene at the distal end of the MHC class Ib region.
Myelin/oligodendrocyte glycoprotein (MOG) is expressed specifically in the central nervous system (CNS) by myelinating glial cells, the oligodendrocytes. The external location of MOG on myelin sheaths and its late expression during myelinogenesis argue for a role of MOG in the completion of myelin and maintenance of its integrity. MOG is a target autoantigen in demyelinating diseases, such as experimental autoimmune encephalomyelitis (EAE) in animals and multiple sclerosis (MS) in humans. We previously located the gene encoding MOG to the major histocompatibility complex (MHC), both in human, by cytogenetics, and in mouse, by analysis of recombinants. To refine the position, we have now selected yeast artificial chromosome clones (YAC) which contain the MOG gene. Physical mapping of the human MOG and the mouse Mog genes by characterization of these YAC clones indicated that the gene is located at the distal end of the major histocompatibility complex (MHC) class Ib region in both species. The human MOG gene lies 60 kilobases (kb) telomeric to HLA-F in a head-to-head orientation; the mouse Mog gene lies 25 (kb) telomeric to H2-M5 in a tail-to-head orientation. These orthologous genes provide markers for comparative analysis of the evolution of the MHC in the two species. The physical mapping of MOG should facilitate analysis of its role in hereditary neurological diseases, and the YAC clones identified here will permit the identification of new genes in the region.


Functional colloidal trimers by quenched electrostatic assembly.
It is shown how to assemble three particles into a single "colloidal trimer". The particles may consist of different materials and be different sizes, and they can be assembled in a particular sequence (i.e. 1-2-3 or 2-1-3 or 2-3-1). Several trimer assemblies are demonstrated, including polystyrene-silica-polystyrene, gold-polystyrene-silver, and gold-silicon-silver. The gold-silicon-silver assembly operates as a catalytic motor, moving rapidly by autoelectrophoresis when placed in a hydrogen peroxide solution. The assemblies are made by allowing oppositely-charged particles to aggregate in a diffusion-limited manner for a time, and then quenching the aggregation by the addition of a nanoparticle coating on one of the particles. We call this method "Quenched Electrostatic Assembly", and it serves as a general, scalable method for synthesizing multi-component colloidal trimers, including those requiring a certain sequential order, but not requiring particular orientations. In addition, when polymer nanoparticles are used to quench the aggregation, they can be fused above their glass transition temperature to produce assemblies that are mechanically stable.