Biotransformation of catechin and extraction of active polysaccharide from green tea leaves via simultaneous treatment with tannase and pectinase.
Green tea is a dietary source of bioactive compounds for human health. Enzymatic treatments induce the bioconversion of bioactive components, which can improve biological activities. In this study, we investigated the effect of simultaneous treatment with tannase and Rapidase on biotransformation of catechins and extraction of polysaccharide from green tea extract (GTE). Tannase and pectinase treatments induced the biotransformation of catechins and altered tea polysaccharide () content. The addition of GTE to the enzyme reaction resulted in a significant increase in degallated catechins, including gallic acid, a product of the tannase reaction (314.5-4076.0 µg mL(-1)) and a reduction in epigallocatechin gallate (EGCG). Biotransformation of catechins improved the radical scavenging activity of GTE. Pectinase treatment led to change of TPS composition in GTE by hydrolyzing polysaccharides. In addition, pectinase-driven hydrolysis in polysaccharides significantly increased TPS-induced Interleukin 6 (IL-6) production in macrophages. In particular, treatment of Rapidase (TPS-Ra) led to the highest IL-6 production among TPS samples, similar to treatment of highly purified pectinase (TPS-GTE), a positive control. Simultaneous processing with tannase and Rapidase can be an efficient method for the extraction of bioactive polysaccharides and biotransformation of catechins with enhanced radical scavenging activity from green tea.


Binding of Candida albicans enolase to plasmin(ogen) results in enhanced invasion of human brain microvascular endothelial cells.
Infection by the human opportunistic fungal pathogen Candida albicans has been increasing over recent years. In an attempt to understand the molecular mechanism of Candida invasion across host tissues, the relationship of C. albicans enolase to human plasminogen/plasmin was investigated. C. albicans enolase is a cell-surface protein and an immunodominant antigen in infected patients' sera. Plasminogen is an abundant plasma protein. Several lines of evidence support the binding of C. albicans enolase to human plasminogen. Firstly, it was found that various Candida strains were able to bind to plasminogen and its active form, plasmin. Secondly, recombinant Candida enolase was retained in a nickel-chelating affinity column matrix that can bind (125)I-labelled plasminogen or plasmin in a dose-dependent manner. Plasmin(ogen)-specific inhibitors, such as epsilon -aminocaproic acid and aprotinin, can effectively block plasmin-binding activity. Thirdly, as with many plasminogen receptors, binding of Candida enolase to plasmin(ogen) is lysine-dependent, whereas little inhibition occurred with arginine, aspartate and glutamate. Fourthly, immobilized enolase enhanced plasminogen's affinity for streptokinase at least tenfold, as demonstrated by its activation of plasmin activity. To elucidate the biological significance of this result, it was demonstrated that the plasmin(ogen)-bound Candida cells were able to induce fibrinolysis activity in a matrix-gel assay. Furthermore, plasmin-bound Candida cells had an increased ability to cross an in vitro blood-brain barrier system. The results given here indicate that Candida enolase is a plasminogen- and plasmin-binding protein and that the interaction of C. albicans enolase with the plasminogen system may contribute to invasion of the tissue barrier.


Cellular and extracellular protein antigens of Treponema pallidum synthesized during in vitro incubation of freshly extracted organisms.
A new medium that permits radiolabeling of freshly extracted cells of Treponema pallidum with [35S]methionine very efficiently has been devised. Although treponemes were not purified free of contaminating rabbit tissue, label was incorporated exclusively into treponemal protein in a linear manner for at least the first 16 h of in vitro incubation. Throughout this period, virtually a full complement of treponemal proteins was synthesized, based on a sodium dodecyl sulfate-polyacrylamide gel electrophoresis comparison of the radiolabeled protein profile with the Coomassie blue-stained profile of gradient-purified treponemes. The radiolabeled protein profiles obtained with three pathogenic strains were very similar but not identical. Using solubilized treponemal extracts and a sensitive radioimmunoprecipitation procedure, we identified the protein antigens of T. pallidum that were recognized by immunoglobulin G antibodies in various rabbit and human syphilitic sera. A simple fractionation procedure has been used to separate soluble and membrane-bound treponemal proteins. A number of the membrane proteins are exposed on the cell surface, since intact radiolabeled treponemes bound antibodies directed against these proteins. In addition, a unique class of low-molecular-weight extracellular treponemal proteins has been identified. The cell surface-exposed proteins were among the earliest proteins recognized by immunoglobulin G antibodies after experimental infection of rabbits with T. pallidum.


Loss of linker histone H1 in cellular senescence.
Cellular senescence is a tumor-suppressing mechanism that is accompanied by characteristic chromatin condensation called senescence-associated heterochromatic foci (SAHFs). We found that individual SAHFs originate from individual chromosomes. SAHFs do not show alterations of posttranslational modifications of core histones that mark condensed chromatin in mitotic chromosomes, apoptotic chromatin, or transcriptionally inactive heterochromatin. Remarkably, SAHF-positive senescent cells lose linker histone H1 and exhibit increased levels of chromatin-bound high mobility group A2 (HMGA2). The expression of N-terminally enhanced green fluorescent protein (EGFP)-tagged histone H1 induces premature senescence phenotypes, including increased levels of phosphorylated p53, p21, and hypophosphorylated Rb, and a decrease in the chromatin-bound endogenous histone H1 level but not in p16 level accumulation or SAHF formation. However, the simultaneous ectopic expression of hemagglutinin-tagged HMGA2 and N-terminally EGFP-tagged histone H1 leads to significant SAHF formation (P < 0.001). It is known that histone H1 and HMG proteins compete for a common binding site, the linker DNA. These results suggest that SAHFs are a novel type of chromatin condensation involving alterations in linker DNA-binding proteins.


Iron deficiency decreases dopamine D1 and D2 receptors in rat brain.
Iron deficiency (ID) in early life is known to alter neurological development and functioning, but data regarding specific effects on dopamine biology are lacking. The objective of this study was to determine the extent of functional alterations in dopamine receptors in two dopaminergic tracts in young, growing, iron-deficient rats. Forty male and 40 female weanling Sprague-Dawley rats were fed either an iron-deficient (ID) diet or control (CN) diet for 6 weeks. ID decreased densities of D(1) and D(2) receptors in the caudate-putamen and decreased D(2) receptor densities in the nucleus accumbens. There were no apparent effects of ID on the affinities for the ligands in either receptor in several brain regions. In situ hybridization studies for both dopamine receptors revealed no significant effect of ID on mRNA expression for either receptor. Iron-deficient rats had a significantly higher ED(50) for raclopride-induced hypolocomotion in male and female rats compared to control rats of each sex. The loss of iron in the striatum due to dietary ID was significantly correlated with the decrease in D(2) receptor density; however, this relationship was not apparent in other brain regions. These experiments thus demonstrate abnormal dopamine receptor density and functioning in several brain regions that are related to brain regional iron loss. Importantly, the impact of ID on dopamine was more pronounced in males than females, demonstrating sex-related different sensitivities to nutrient deprivation.


Double-Edged Role of Interleukin 17A in Streptococcus pneumoniae Pathogenesis During Influenza Virus Coinfection.
We sought to determine the role of host interleukin 17A (IL-17A) response against colonizing Streptococcus pneumoniae, and its transition to a pathogen during coinfection with an influenza virus, influenza A H1N1 A/Puerto Rico/8/1934 (PR8). Wild-type (WT) C57BL/6 mice were intranasally inoculated with S. pneumoniae serotype 6A to establish colonization and later infected with the influenza strain, PR8, resulting in invasive S. pneumoniae disease. The role of the IL-17A response in colonization and coinfection was investigated in WT, RoRγt-/- and RAG1-/- mice with antibody-mediated depletion of IL-17A (WT) and CD90 cells (RAG1-/-). RAG1-/- mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoRγt-/- mice also had reduced clearance. S. pneumoniae-PR8 coinfection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced S. pneumoniae invasive disease. RoRγt-/- mice also had reduced S. pneumoniae disease in a coinfection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced S. pneumoniae invasion in RAG1-/- mice. Our data show that although IL-17A reduces S. pneumoniae colonization, coinfection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and S. pneumoniae disease in the nasopharynx.


Regulation of hard α-keratin mechanics via control of intermediate filament hydration: matrix squeeze revisited.
Mammalian hard α-keratins are fibre-reinforced biomaterials that consist of 10 nm intermediate filaments (IFs) embedded in an elastomeric protein matrix. Recent work suggests that the mechanical properties of IFs are highly sensitive to hydration, whereas hard α-keratins such as wool, hair and nail are relatively hydration insensitive. This raises the question of how mammalian keratins remain stiff in water. The matrix squeeze hypothesis states that the IFs in hard α-keratins are stiffened during an air-drying step during keratinization, and subsequently locked into a dehydrated state via the oxidation and cross-linking of the keratin matrix around them. The result is that even when hard α-keratins are immersed in water, their constituent IFs remain essentially 'dry' and therefore stiff. This hypothesis makes several predictions about the effects of matrix abundance and function on hard α-keratin mechanics and swelling behaviour. Specifically, it predicts that high matrix keratins in water will swell less, and have a higher tensile modulus, a higher yield stress and a lower dry-to-wet modulus ratio. It also predicts that disruption of the keratin matrix in water should lead to additional swelling, and a drop in modulus and yield stress. Our results are consistent with these predictions and suggest that the keratin matrix plays a critical role in governing the mechanical properties of mammalian keratins via control of IF hydration.


Modeling the Effects of Duration and Size of the Control Zones on the Consequences of a Hypothetical African Swine Fever Epidemic in Denmark.
African swine fever (ASF) is a notifiable infectious disease. The disease is endemic in certain regions in Eastern Europe constituting a risk of ASF spread toward Western Europe. Therefore, as part of contingency planning, it is important to continuously explore strategies that can effectively control an epidemic of ASF. A previously published and well documented simulation model for ASF virus spread between herds was used to examine the epidemiologic and economic impacts of the duration and size of the control zones around affected herds. In the current study, scenarios were run, where the duration of the protection and surveillance zones were reduced from 50 and 45 days to 35 and 25 days or to 35 and 25 days, respectively. These scenarios were run with or without enlargement of the surveillance zone around detected herds from 10 to 15 km. The scenarios were also run with only clinical or clinical and serological surveillance of herds within the zones. Sensitivity analysis was conducted on influential input parameters in the model. The model predicts that reducing the duration of the protection and surveillance zones has no impact on the epidemiological consequences of the epidemics, while it may result in a substantial reduction in the total economic losses. In addition, the model predicts that increasing the size of the surveillance zone from 10 to 15 km may reduce both the epidemic duration and the total economic losses, in case of large epidemics. The ranking of the control strategies by the total costs of the epidemics was not influenced by changes of input parameters in the sensitivity analyses.


High grazer toxicity of [D-Asp(3),(E)-Dhb(7)]microcystin-RR of Planktothrix rubescens as compared to different microcystins.
Planktothrix rubescens, the dominant cyanobacterium in Lake Zürich, is generally considered to be toxic to zooplankton. The major toxin was determined by NMR spectroscopy and chemical analysis to be [D-Asp(3),(E)-Dhb(7)]microcystin-RR. The compound was isolated in high purity, and its 24-h acute grazer toxicity was compared with microcystin-LR, microcystin-RR, microcystin-YR, and nodularin using a Thamnocephalus platyurus bioassay. Based on LC(50) values [D-Asp(3),(E)-Dhb(7)]microcystin-RR was the most toxic microcystin tested. Nodularin was slightly more toxic under the conditions of the assay. The large number of individuals available for the grazer bioassay allowed the determination of dose-response curves of the different microcystins. These curves showed marked differences in their steepness. Microcystin-RR, which had nearly the same LC(50) as microcystin-LR and microcystin-YR, exhibited a very flat dose-response curve. This flat curve indicates that, for some individuals, lower concentrations of this microcystin are much more toxic than are the other two microcystins. Mortality of 100% requires much higher concentrations of microcystin-RR, indicating the resistance of some animals to the toxin. The purified [D-Asp(3),(E)-Dhb(7)]microcystin-RR exhibited a higher molar absorption coefficient determined by quantitative amino acid analysis than the coefficients generally used for other microcystins. This observation has consequences for the risk assessment for microcystins and makes a structural determination of microcystins an absolute requirement. The presence of the dehydrobutyrine residue may be the reason for the higher specific toxicity of [D-Asp(3),(E)-Dhb(7)]microcystin-RR when compared to the N-methyldehydroalanine-containing microcystins.


The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization.
Patients with classic fibrodysplasia ossificans progressiva, a disorder characterized by extensive extraskeletal endochondral bone formation, share a recurrent mutation (R206H) within the glycine/serine-rich domain of ACVR1/ALK2, a bone morphogenetic protein type I receptor. Through a series of in vitro assays using several mammalian cell lines and chick limb bud micromass cultures, we determined that mutant R206H ACVR1 activated BMP signaling in the absence of BMP ligand and mediated BMP-independent chondrogenesis that was enhanced by BMP. We further investigated the interaction of mutant R206H ACVR1 with FKBP1A, a glycine/serine domain-binding protein that prevents leaky BMP type I receptor activation in the absence of ligand. The mutant protein exhibited reduced binding to FKBP1A in COS-7 simian kidney cell line assays, suggesting that increased BMP pathway activity in COS-7 cells with R206H ACVR1 is due, at least in part, to decreased binding of this inhibitory factor. Consistent with these findings, in vivo analyses of zebrafish embryos showed BMP-independent hyperactivation of BMP signaling in response to the R206H mutant, resulting in increased embryonic ventralization. These data support the conclusion that the mutant R206H ACVR1 receptor in FOP patients is an activating mutation that induces BMP signaling in a BMP-independent and BMP-responsive manner to promote chondrogenesis, consistent with the ectopic endochondral bone formation in these patients.


Reducing thermal crosstalk in ten-channel tunable slotted-laser arrays.
Given the tight constraints on the wavelength stability of sources in optical networks, the thermal crosstalk between operating devices in a ten-channel thermally-tunable slotted laser array for DWDM applications has been investigated. It was found experimentally the current standard thermal solution with the laser array chip mounted on an AlN carrier does not allow for wavelength stability of ± 25 GHz ( ± 2 K) with a temperature rise of 5 K measured in a device with 100 mA (CW) applied to a neighbouring laser (device spacing = 360 µm). A combined experimental/numerical approach revealed solid state submounts comprising diamond or highly ordered pyrolytic graphite are inadequate to reduce crosstalk below an allowable level. Numerical simulations of advanced cooling technologies reveal a microfluidic enabled substrate would reduce thermal crosstalk between operational devices on the chip to acceptable levels. Critically our simulations show this reduced crosstalk is not at the expense of device tunability as the thermal resistance of individual lasers remains similar for the base and microfluidic cases.


[Parasitoids of Chrysomya megacephala (Fabricius) collected in Itumbiara, Goias, Brazil].
This study determined the species of parasitoids associated with Chrysomya megacephala, collected on bovine kidney baits, in Itumbiara, State of Goias, Brazil. The pupae were obtained by flotation. They were individually placed in gelatin capsules until the emergence of the adult flies or their parasitoids. The overall prevalence of parasitism was 18.6%. Brachymeria podagrica, Nasonia vitripennis and Pachycrepoideus vindemiae presented frequencies of 8.6%, 8.6% and 1.4%, respectively. This work reports for the first time the occurrence of Brachymeria podagrica in pupae of Chrysomya megacephala.


Non-Invasive Evaluation of Hepatic Fibrosis: The Diagnostic Performance of Magnetic Resonance Elastography in Patients with Viral Hepatitis B or C.
To compare the accuracy of magnetic resonance elastography (MRE) with that of aspartate aminotransferase-to-platelet ratio index (APRI) for estimating the stage of hepatic fibrosis in patients with chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection. We retrospectively enrolled 160 patients with chronic hepatitis and 25 healthy living liver donors. Fibrosis stage (METAVIR, F0 to F4) was determined histopathologically for all patients. APRI was recorded at the time of histopathologic examination and liver stiffness values were measured on MRE quantitative stiffness maps. The cutoff values, sensitivity, and specificity of MRE and APRI for each fibrosis stage were determined using receiver operating characteristic (ROC) analysis. MRE had a significantly greater area under the ROC curve than APRI score for discriminating among METAVIR stages F2-F4. Using a cutoff value of 2.80 kPa, MRE had a sensitivity of 94.4% and a specificity of 97.8% for detecting significant fibrosis (≥F2). There were no significant differences in fibrosis stage between patients with HBV and those with HCV infection. For ≥F2, the cutoffs were 2.47 kPa (100% sensitivity), 2.80 kP (maximum sum of sensitivity and specificity), and 3.70 kPa (100% specificity). MRE is a more accurate modality than APRI for detecting significant fibrosis in patients with chronic HBV or HCV infection. Antiviral treatment should be considered in patients with liver stiffness values ≥ 2.8 kPa.


Single-cell analysis of insulin-regulated fatty acid uptake in adipocytes.
Increased body fat correlates with the enlargement of average fat cell size and reduced adipose tissue insulin sensitivity. It is currently unclear whether adipocytes, as they accumulate more triglycerides and grow in size, gradually become less insulin sensitive or whether obesity-related factors independently cause both the enlargement of adipocyte size and reduced adipose tissue insulin sensitivity. In the first instance, large and small adipocytes in the same tissue would exhibit differences in insulin sensitivity, whereas, in the second instance, adipocyte size per se would not necessarily correlate with insulin response. To analyze the effect of adipocyte size on insulin sensitivity, we employed a new single-cell imaging assay that resolves fatty acid uptake and insulin response in single adipocytes in subcutaneous adipose tissue explants. Here, we report that subcutaneous adipocytes are heterogeneous in size and intrinsic insulin sensitivity. Whereas smaller adipocytes respond to insulin by increasing lipid uptake, adipocytes with cell diameters larger than 80-100 microm are insulin resistant. We propose that, when cell size approaches a critical boundary, adipocytes lose insulin-dependent fatty acid transport. This negative feedback mechanism may protect adipocytes from lipid overload and restrict further expansion of adipose tissue, which leads to obesity and metabolic complications.


PTH elevates inositol polyphosphates and diacylglycerol in a rat osteoblast-like cell line.
Parathyroid hormone (PTH)-stimulated signal transduction through mechanisms alternate to adenosine 3',5'-cyclic monophosphate (cAMP) production were studied in UMR 106-01 cells, a cell line with an osteoblastic phenotype. PTH produced transient, dose-related increases in cytosolic calcium [( Ca2+]i), inositol trisphosphates, and diacylglycerol (DAG). Both inositol 1,4,5-trisphosphate (Ins-1,4,5P3) and inositol 1,3,4-trisphosphate (Ins-1,3,4P3) production were rapidly stimulated by PTH. Consistent with the production of Ins-1,3,4P3, rapid stimulation of late eluting inositol tetrakisphosphate was observed. The effects on the inositol phosphates were induced rapidly, consistent with roles as signals for changes in [Ca2+]i. In saponin-permeabilized UMR 106-01 cells, Ins-1,4,5P3 stimulated 45Ca release from a nonmitochondrial intracellular pool. Thus the hypothesis that PTH-stimulated Ins-1,4,5P3 production initiates Ca2+ release and contributes to transient elevations of [Ca2+]i is supported. Pretreatment of UMR 106-01 cells with pertussis toxin had no effect on PTH stimulation of inositol phosphates. Pertussis toxin reduced PTH-stimulated elevations of [Ca2+]i, but cAMP analogues had an even greater effect than pertussis toxin. These data suggest that stimulation of cAMP production during PTH stimulation may negatively affect production of rises in [Ca2+]i during PTH stimulation. The inactivation of the inhibitory G protein of adenylate cyclase by pertussis toxin could explain its action similar to cAMP analogues. Cyclic nucleotides diminish the effects of PTH on [Ca2+]i, probably interacting on a biochemical step subsequent to or independent of Ins-1,4,5P3 release.


Incidence of ambulatory care visits after needlestick and sharps injuries among healthcare workers in Taiwan: a nationwide population-based study.
Healthcare professionals have a high risk of needlestick and sharps injuries (NSIs), which have a high potential for disease transmission. Ambulatory care follow up is essential, but is usually overlooked. This study aimed to investigate the annual and cumulative (age-, sex-, and subtype-specific) incidences of ambulatory care visits after NSIs. This study was also designed to evaluate the incidences of blood-borne diseases associated with NSIs among Taiwanese health professionals in Taiwan between 2004 and 2010. Data were obtained from the National Health Insurance Research Database, which contains anonymized records representing approximately 99% of the Taiwan population. A total of 4443 nurse healthcare workers (NHCWs) and 3138 non-nurse healthcare workers (NNHCWs), including physicians, medical technologists, and other health professionals were included in this longitudinal study. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The Mantel-Haenszel method was used to adjust for sex, age, and type of affiliation. Results showed that the annual incidence of ambulatory care visits of NHCWs increased from 0.7% in 2004 to 1.9% in 2010; this incidence was significantly higher than that of NNHCWs (from 0.3% in 2004 to 0.5% in 2010) in any yearly comparison (p < 0.05). The sex-adjusted 7-year cumulative incidence rate was 3.23 (95% CI = 1.23-8.45) in males and 3.92 (95% CI = 2.70-5.69) in females (p < 0.05). The age-adjusted 7-year cumulative incidence rate was 2.74 (95% CI = 1.99-3.77) and 2.14 (95% CI = 1.49-3.07) in subjects ≤ 30 and ≥31 years old, respectively (p < 0.0005). The affiliation-adjusted 7-year cumulative incidence rate was 1.89 (95% CI = 1.21-2.94) in medical centers and 3.33 (95% CI = 2.51-4.41) in nonmedical centers (p < 0.01). In conclusion, NSIs increased steadily from 2004 to 2010 in Taiwan with NHCWs having higher NSIs incidences than NNHCWs. A routine ambulatory care visit after NSIs can prevent blood-borne transmission, especially for NHCWs. Educational programs may be helpful for reducing the incidence of NSIs and increasing ambulatory care visit ratios after NSIs.


Advanced Photoresponsive Materials Using the Metal-Organic Framework Approach.
When fabricating macroscopic devices exploiting the properties of organic chromophores, the corresponding molecules need to be condensed into a solid material. Since optical absorption properties are often strongly affected by interchromophore interactions, solids with a well-defined structure carry substantial advantages over amorphous materials. Here, the metal-organic framework (MOF)-based approach is presented. By appropriate functionalization, most organic chromophores can be converted to function as linkers, which can coordinate to metal or metal-oxo centers so as to yield stable, crystalline frameworks. Photoexcitations in such chromophore-based MOFs are surveyed, with a special emphasis on light-switchable MOFs from photochromic molecules. The conventional powder form of MOFs obtained using solvothermal approaches carries certain disadvantages for optical applications, such as limited efficiency resulting from absorption and light scattering caused by the (micrometer-sized) powder particles. How these problems can be avoided by using MOF thin films is demonstrated.


Treatment of elderly patients with glioblastoma: a systematic evidence-based analysis.
Despite improvements in survival with aggressive chemoradiation, outcomes for patients diagnosed as having glioblastoma multiforme (GBM) remain poor. Survival is further limited in elderly patients, who are often unable to tolerate multimodality therapy. The appropriate treatment approach for elderly patients (aged >65 years) with GBM remains unclear. While the literature supports the use of standard radiotherapy (60 Gy), several recent studies have suggested that treatment with temozolomide monotherapy or short-course radiotherapy may be a reasonable alternative. To review literature reporting survival data related to treatment of elderly patients with GBM using either temozolomide alone or radiotherapy alone. We performed a systematic review to identify articles from the temozolomide era (2005-present) that reported survival data related to treatment of elderly patients with GBM using either temozolomide alone or radiotherapy alone, with consideration of O6-methylguanine-DNA-methyltransferase gene (MGMT) promoter methylation status. PubMed was searched for articles between January 1, 2005, and August 31, 2013, using the search terms glioblastoma, elderly, temozolomide, radiation, hypofractionated, and survival, and references from relevant articles were searched. Selected articles reported overall survival data associated with either temozolomide alone or radiotherapy alone in elderly patients (aged ≥60 years) with GBM; articles were excluded if they did not report survival data from radiotherapy alone or temozolomide alone, were not restricted to an elderly population, did not report original data, were not restricted to patients with primary GBM, were a subgroup analysis of a prior article, were a case report, or could not be located in entirety. Articles were interrogated as per the criteria designated by the Oxford Centre for Evidence-Based Medicine to determine the level of evidence presented, and data from level 1 and 2 studies were used for analysis. From a review of 185 articles, 23 were selected for inclusion and final analysis. From these, we identified 2 level 1 studies and 1 level 2 study that reported overall survival in elderly patients treated with temozolomide alone, and 4 level 1 studies and 2 level 2 studies that reported overall survival in elderly patients treated with radiotherapy alone. This review of the literature revealed several limitations. First, there is a paucity of randomized clinical studies comparing temozolomide alone with radiotherapy alone in elderly patients with GBM. Second, there is a lack of coherence in the literature for the definition of elderly. Third, the treatment paradigms used are not consistent from study to study. Regardless, the available data did allow the formulation of a recommendation based on level 1 and 2 data. The literature supports the use of hypofractionated radiotherapy or temozolomide monotherapy in the treatment of elderly patients with GBM. In patients with MGMT promoter methylation, temozolomide monotherapy may have greater benefit than radiotherapy.


Test-retest reliability of three different countermovement jumping tests.
In studies of physical performance comprising muscle strength and power, a vertical jump is a test method that frequently is used. It is important to have access to accurate measuring tools providing data with high reproducibility. Studies have shown that body composition also may play an important part in physical performance. The purpose of this study was to determine test-retest reliability for 3 different kinds of vertical jumps and to correlate jump height with body composition. Thirty-four normally trained subjects (women n = 17) between 18 and 25 years participated. Test-retest, on 3 kinds of vertical jumps, was performed with a median of 7 days between jumps. Methods used were a countermovement jump (CMJ) on a contact mat, with and without arm swing, and an Abalakow jump (AJ) using measuring tape, with arm swing. Body composition was assessed with the use of bioelectric impedance analysis. The results showed that high intraclass correlation coefficients (ICCs) were observed between testing occasions for all 3 vertical jumps (ICC between 0.48 and 0.88). The AJ in women presented the lowest ICC. Also the correlation between CMJ and AJ was high (rs = 0.88). Moderate-to-high correlations could be shown between body composition and CMJ in women (rs = -0.57-0.76). In conclusion, very high test-retest reliability for CMJ on a contact mat was found. For the AJ using a measuring tape, ICC were overall high, but a moderate nonsignificant ICC were found in women, indicating poor reproducibility. The data from the CMJ and AJ may be compared if approximately 25% of the AJ value is subtracted. In practice, this means that vertical jump tests have high reproducibility and can be used as measures of power development.


Expectations, goals, and perceived effectiveness of child health supervision: a study of mothers in a pediatric practice.
The purpose of the study was to assess parent expectations and goals in child health supervision and variability by socioeconomic status (SES), family size, social support, and pediatrician. Home interviews were conducted with mothers and their pediatricians were surveyed. Two hundred mothers with at least one child age 2-3 years who see one of five pediatricians in a staff model health maintenance organization were asked to participate. Mothers' and pediatricians' goals in the following seven areas of health supervision were assessed: biomedical, development, behavior, family functioning, safety education, and interpersonal and system interaction. Mothers stated physicians were their main source of parenting information. Assurance of physical health and normal development were more important than discussion of behavioral, family, or safety issues. Mothers of low SES were more likely to feel that physical aspects of health should be the focus and were less interested in psychosocial issues. Physicians stressed interpersonal, safety, and behavioral goals more than mothers. Individual physician responses did not predict the responses of mothers in their practice. Our data suggest either that mothers do not feel that psychosocial and safety issues are the highest priorities in health supervision or that physicians are not effectively reaching mothers on these issues.


Nursing inputs and outcomes of hospital care: an empirical analysis of Ontario's acute-care hospitals.
The authors analyze the association between intensity of nursing care (as measured by nursing hours per patient day), hospital bed days, and patient outcomes in acute-care hospitals in the province of Ontario, Canada, to determine whether higher levels of nursing inputs are associated with shorter lengths of stay (LOS) and, if so, whether these shorter LOS are achieved at the expense of health outcomes. After controlling for supply of nurses, workload, community characteristics, and hospital type, the authors found that nursing hours per patient day had a significant negative effect on LOS but had no significant effect on patient satisfaction, hospital mortality, or readmission rates. Further, there was no evidence that shorter than expected LOS were associated with poorer patient health. Such information is relevant for efforts to deploy efficient mixes of health-care resources and to identify future human resource requirements to support the efficient provision of health human resources.


Desistance From Intimate Partner Violence: A Conceptual Model and Framework for Practitioners for Managing the Process of Change.
Intimate partner violence (IPV) is an international issue that social and criminal justice workers will encounter regularly. It has been identified that men can, and do stop using, or desist from, IPV although it is unclear how this process of change develops. This article introduces a conceptual model to outline how the process of desistance evolves and what it encompasses. Using thematic analysis of interview data from partner-violent men, survivors, and treatment facilitators, the resulting model demonstrates that the process of change is a dynamic one where men's use of, and cessation from, violence needs to be understood within the context of each individual's life. Three global themes were developed: (a) lifestyle behaviors (violent): what is happening in the men's lives when they use violence; (b) catalysts for change: the triggers and transitions required to initiate the process of change; and (c) lifestyle behaviors (non-violent): what is different in the men's lives when they have desisted from IPV. The purpose of this model is to offer a framework for service providers to assist them to manage the process of change in partner-violent men.


Spectrum of epithelial neoplasms in end-stage renal disease: an experience from 66 tumor-bearing kidneys with emphasis on histologic patterns distinct from those in sporadic adult renal neoplasia.
Most (up to 71%) of renal cell neoplasms occurring in patients with end-stage renal disease (ESRD), particularly with acquired cystic disease of the kidney (ACDK), have been reported to be papillary renal cell carcinoma (RCC). Our initial experience with tumors in such a setting indicated that many tumors were histologically difficult to classify into the known subtypes of RCC or had features that were different from those in sporadically occurring RCCs. In this study on 66 ESRD kidneys (52 of which showed features of ACDK) removed because tumors were detected in them, we found two major groups of RCC. Overall, there were 261 grossly identified tumors in these kidneys, and many additional tumors were observed on microscopic evaluation in some. Of the two major groups of RCCs, one consisted of tumors similar to those seen in sporadic settings (ie, clear-cell, papillary, and chromophobe RCC), and these formed the dominant mass in 12 (18%), 10 (15%), and 5 (8%) of the 66 kidneys, respectively. The other group consisted of two subtypes of RCC that appear quite unique to ESRD. The more common tumor that we have designated as "acquired cystic disease-associated RCC" was seen as the dominant mass in 24 (36%) of 66 of the kidneys, and it formed the most common tumor type among the smaller nondominant masses, as well. It was characterized by a typical microcystic architecture, eosinophilic cytoplasm with Fuhrman's grade 3 nuclei, and frequent association with intratumoral oxalate crystals. Additionally, these tumors frequently, but usually focally, exhibited papillary architecture, and clear cytoplasm. These tumors occurred only in kidneys with ACDK, and not in noncystic ESRD. The other category was "clear-cell papillary RCC of the end-stage kidneys," present as the dominant mass in 15 (23%) of the 66 kidneys and occurring in both the ACDK and noncystic ESRD. These predominantly cystic tumors showed prominent papillary architecture with purely clear-cell cytology. Immunohistochemical studies in tumors with histology similar to the known subtypes of sporadic RCC showed immunoprofiles similar to that reported in sporadically occurring tumors. The two subtypes of RCC unique to ESRD had distinctive immunoprofiles supporting their separate morphologic subcategorization. Only the acquired cystic disease-associated RCC showed lymph node metastases in 2 cases and sarcomatoid features in 2 more cases. One of the latter 2 died with widespread metastatic disease within 34 months of nephrectomy. Thus, a broad spectrum of renal cell tumors exist in ESRD, only some of which resemble the sporadic RCCs. Acquired cystic disease-associated RCC is the commonest tumor subtype in ESRD, and biologically it appears to be more aggressive than the other tumor subtypes in ESRD.


Exercises for mechanical neck disorders.
Neck pain is common, disabling and costly. Exercise is one treatment approach. To assess the effectiveness of exercises to improve pain, disability, function, patient satisfaction, quality of life and global perceived effect in adults with neck pain. We searched MEDLINE, MANTIS, ClinicalTrials.gov and three other computerized databases up to between January and May 2014 plus additional sources (reference checking, citation searching, contact with authors). We included randomized controlled trials (RCTs) comparing single therapeutic exercise with a control for adults suffering from neck pain with or without cervicogenic headache or radiculopathy. Two review authors independently conducted trial selection, data extraction, 'Risk of bias' assessment and clinical relevance. The quality of the evidence was assessed using GRADE. Meta-analyses were performed for relative risk and standardized mean differences (SMD) with 95% confidence intervals (CIs) after judging clinical and statistical heterogeneity. Twenty-seven trials (2485 analyzed /3005 randomized participants) met our inclusion criteria.For acute neck pain only, no evidence was found.For chronic neck pain, moderate quality evidence supports 1) cervico-scapulothoracic and upper extremity strength training to improve pain of a moderate to large amount immediately post treatment [pooled SMD (SMDp) -0.71 (95% CI: -1.33 to -0.10)] and at short-term follow-up; 2) scapulothoracic and upper extremity endurance training for slight beneficial effect on pain at immediate post treatment and short-term follow-up; 3) combined cervical, shoulder and scapulothoracic strengthening and stretching exercises varied from a small to large magnitude of beneficial effect on pain at immediate post treatment [SMDp -0.33 (95% CI: -0.55 to -0.10)] and up to long-term follow-up and a medium magnitude of effect improving function at both immediate post treatment and at short-term follow-up [SMDp -0.45 (95%CI: -0.72 to -0.18)]; 4) cervico-scapulothoracic strengthening/stabilization exercises to improve pain and function at intermediate term [SMDp -14.90 (95% CI:-22.40 to -7.39)]; 5) Mindfulness exercises (Qigong) minimally improved function but not global perceived effect at short term. Low evidence suggests 1) breathing exercises; 2) general fitness training; 3) stretching alone; and 4) feedback exercises combined with pattern synchronization may not change pain or function at immediate post treatment to short-term follow-up. Very low evidence suggests neuromuscular eye-neck co-ordination/proprioceptive exercises may improve pain and function at short-term follow-up.For chronic cervicogenic headache, moderate quality evidence supports static-dynamic cervico-scapulothoracic strengthening/endurance exercises including pressure biofeedback immediate post treatment and probably improves pain, function and global perceived effect at long-term follow-up. Low grade evidence supports sustained natural apophyseal glides (SNAG) exercises.For acute radiculopathy, low quality evidence suggests a small benefit for pain reduction at immediate post treatment with cervical stretch/strengthening/stabilization exercises. No high quality evidence was found, indicating that there is still uncertainty about the effectiveness of exercise for neck pain. Using specific strengthening exercises as a part of routine practice for chronic neck pain, cervicogenic headache and radiculopathy may be beneficial. Research showed the use of strengthening and endurance exercises for the cervico-scapulothoracic and shoulder may be beneficial in reducing pain and improving function. However, when only stretching exercises were used no beneficial effects may be expected. Future research should explore optimal dosage.


Gender Differences in Physician Service Provision Using Medicare Claims Data.
To determine differences in the provision of Medicare services based on physician gender in the United States. Participants included all 2013 Medicare fee-for-service physicians and their patients, a population that is predominantly older than 65 years. The 2013 Medicare Provider Utilization and Payment Data for services rendered between January 1, 2013, and December 31, 2013, were combined with the 2015 Physician Compare National Downloadable files and 2015 Berenson-Eggers Type of Service classification files. Total fee-for-service Medicare payments and Healthcare Common Procedure Coding System procedure codes for all fee-for-service beneficiaries were aggregated according to physician gender, specialty, years since medical school graduation, and type of service classifications. Excluding drug reimbursement, the mean total Medicare payments per female physician, compared with those for male physicians, were 41% in surgical specialties, 72% in hospital-based specialties, and 55% across all specialties (P<.001). The mean overall number of unique beneficiary visits per female physician was 59% of that for male physicians (P<.001). By using the Berenson-Eggers Type of Service classification, procedures and other services by female physicians were of 54% lower overall average intensity (allowed payments/number of unique patients) compared with those of male physicians. These differences persisted irrespective of years since medical school graduation (P<.001). Female physicians had smaller average total Medicare payments and fewer unique beneficiary visits than male physicians in the care of fee-for-service Medicare beneficiaries in 2013. The differences persisted across specialty types and years in practice. These data can identify variation but cannot determine causation or explain the reasons behind gender differences. These findings suggest, but do not prove, that female physician Medicare payments are lower due to different practice patterns, consisting of fewer patients cared for and lower intensity of care.


Prevalence of health promotion programs in primary health care units in Brazil.
Assessment of prevalence of health promotion programs in primary health care units within Brazil's health system. We conducted a cross-sectional descriptive study based on telephone interviews with managers of primary care units. Of a total 42,486 primary health care units listed in the Brazilian Unified Health System directory, 1,600 were randomly selected. Care units from all five Brazilian macroregions were selected proportionally to the number of units in each region. We examined whether any of the following five different types of health promotion programs was available: physical activity; smoking cessation; cessation of alcohol and illicit drug use; healthy eating; and healthy environment. Information was collected on the kinds of activities offered and the status of implementation of the Family Health Strategy at the units. Most units (62.0%) reported having in place three health promotion programs or more and only 3.0% reported having none. Healthy environment (77.0%) and healthy eating (72.0%) programs were the most widely available; smoking and alcohol use cessation were reported in 54.0% and 42.0% of the units. Physical activity programs were offered in less than 40.0% of the units and their availability varied greatly nationwide, from 51.0% in the Southeast to as low as 21.0% in the North. The Family Health Strategy was implemented in most units (61.0%); however, they did not offer more health promotion programs than others did. Our study showed that most primary care units have in place health promotion programs. Public policies are needed to strengthen primary care services and improve training of health providers to meet the goals of the agenda for health promotion in Brazil.


An ex-vivo human intestinal model to study Entamoeba histolytica pathogenesis.
Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion.


Moving backwards, moving forward: the experiences of older Filipino migrants adjusting to life in New Zealand.
To explore the experiences of older Filipino migrants adjusting to living permanently in New Zealand. The qualitative descriptive approach taken in this study involved 17 individual face-to-face interviews of older Filipino migrants in New Zealand. Three main themes emerged from the data. The first theme was "moving backwards and moving forward", which described how these older Filipino migrants adjusted to challenges they experienced with migration. The second theme was "engaging with health services" and presented challenges relating to the New Zealand healthcare system, including a lack of knowledge of the nature of health services, language barriers, and differences in cultural views. The third theme, "new-found home", highlighted establishing a Filipino identity in New Zealand and adjusting to the challenges of relocation. Adjustment to life in New Zealand for these older Filipino migrants meant starting over again by building new values through learning the basics and then moving forward from there.


[Epstein-Barr virus-associated post-transplant lymphoproliferative disorder diagnosed by the episode of intestinal perforation following allogeneic hematopoietic stem cell transplantation].
A 64-year-old man was diagnosed as having acute myeloid leukemia. We performed sequential treatment with chemotherapy and reduced-intensity stem cell transplantation from an unrelated donor while the patient was in partial remission. After engraftment, he developed acute graft-versus-host disease of the gut on day 42 and steroid therapy was started. Despite transient aggravation of diarrhea, his symptoms slowly improved and the dose of steroid was tapered. On day 159, he complained of acute left lower abdominal pain. A CT scan showed perforation of the digestive tract and ileectomy was performed. At surgery, multiple ulcers of the intestine were found and one of the ulcers was perforated. Pathologically, transmural and diffuse proliferation of atypical cells in the ulcer were confirmed. Since these cells were positive for CD20 and Epstein-Barr-virus (EBV) encoded RNA, we made a diagnosis of EBV-associated post-transplant lymphoproliferative disorder (PTLD). Reduction in the dose of immunosuppressive agents and rituximab led to complete remission of PTLD. PTLD after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is relatively rare, and the development of gastrointestinal perforation after allo-HSCT is very rare.


Prostaglandin receptors in lower segment myometrium during gestation and labor.
To determine if expression of relaxatory prostaglandin (PG) E2 receptors (EP2 isoform) and contractile PG F receptors (FP isoform) changes during gestation and with labor in pregnant human myometrium. Lower segment myometrium was removed at cesarean from four groups of parturients (preterm [28-36 weeks] or term [37-41 weeks], either in or not in labor, ten per group). Myometrial RNA was isolated and used for reverse transcription-polymerase chain reaction (PCR) analysis with specific primer sets for human smooth muscle protein calponin and PGEP2 or FP receptor isoform mRNA. Polymerase chain reaction products were electrophoresed on gels and visualized, band intensity was measured, and EP2 and FP receptor expression was normalized to calponin. Reverse transcription-PCR yielded products of expected sizes, and restriction enzyme cleavage confirmed identities. Prostaglandin EP2 receptor isoform mRNA expression (relative to calponin mRNA) was significantly greater in the preterm, no labor group (1.28+/-0.22, mean +/-standard error of the mean [SE]) compared with the term, no labor group (0.71+/-0.09) (P < .05 Student-Neuman-Kuels) and declined significantly with gestational age in patients not in labor (R = -.446, P = .001). Prostaglandin FP receptor isoform mRNA expression was significantly less in the term, no labor group (0.61+/-0.06) compared with all others (P < .02 Student-Neuman-Kuels). Prostaglandin FP receptor expression declined significantly with gestational age in patients not in labor (R = -.646, P = .012) and increased significantly with labor at term. Changes in prostaglandin EP2 receptor isoform expression are consistent with influence on maintenance of quiescence. Labor at term is associated with a significant increase in FP receptor expression, consistent with influence on contraction. The balance between the two receptor isoforms might mediate myometrial contractility.


Item-level psychometrics of the ADL instrument of the Korean National Survey on persons with physical disabilities.
The aim of this study is to investigate the psychometrics of the 12 items of an instrument assessing activities of daily living (ADL) using an item response theory model. A total of 648 adults with physical disabilities and having difficulties in ADLs were retrieved from the 2014 Korean National Survey on People with Disabilities. The psychometric testing included factor analysis, internal consistency, precision, and differential item functioning (DIF) across categories including sex, older age, marital status, and physical impairment area. The sample had a mean age of 69.7 years old (SD = 13.7). The majority of the sample had lower extremity impairments (62.0%) and had at least 2.1 chronic conditions. The instrument demonstrated unidimensional construct and good internal consistency (Cronbach's alpha = 0.95). The instrument precisely estimated person measures within a wide range of theta values (-2.22 logits < θ < 0.27 logits) with a reliability of 0.9. Only the changing position item demonstrated misfit (χ2 = 36.6, df = 17, p = 0.0038), and the dressing item demonstrated DIF on the impairment type (upper extremity/others, McFadden's Pseudo R 2 > 5.0%). Our findings indicate that the dressing item would need to be modified to improve its psychometrics. Overall, the ADL instrument demonstrates good psychometrics, and thus, it may be used as a standardized instrument for measuring disability in rehabilitation contexts. However, the findings are limited to adults with physical disabilities. Future studies should replicate psychometric testing for survey respondents with other disorders and for children.


Regulation of mammalian Gli proteins by Costal 2 and PKA in Drosophila reveals Hedgehog pathway conservation.
Hedgehog (Hh) signaling activates full-length Ci/Gli family transcription factors and prevents Ci/Gli proteolytic processing to repressor forms. In the absence of Hh, Ci/Gli processing is initiated by direct Pka phosphorylation. Despite those fundamental similarities between Drosophila and mammalian Hh pathways, the differential reliance on cilia and some key signal transduction components had suggested a major divergence in the mechanisms that regulate Ci/Gli protein activities, including the role of the kinesin-family protein Costal 2 (Cos2), which directs Ci processing in Drosophila. Here, we show that Cos2 binds to three regions of Gli1, just as for Ci, and that Cos2 functions to silence mammalian Gli1 in Drosophila in a Hh-regulated manner. Cos2 and the mammalian kinesin Kif7 can also direct Gli3 and Ci processing in fly, underscoring a fundamental conserved role for Cos2 family proteins in Hh signaling. We also show that direct PKA phosphorylation regulates the activity, rather than the proteolysis of Gli in Drosophilia, and we provide evidence for an analogous action of PKA on Ci.


Spectroscopic signatures of proton transfer dynamics in the water dimer cation.
Using full-dimensional EOM-IP-CCSD/aug-cc-pVTZ potential energy surfaces, the photoelectron spectrum, vibrational structure, and ionization dynamics of the water dimer radical cation, (H(2)O)(2) (+), were computed. We also report an experimental photoelectron spectrum which is derived from photoionization efficiency measurements and compares favorably with the theoretical spectrum. The vibrational structure is also compared to the recent experimental work of Gardenier et al. [J. Phys. Chem. A 113, 4772 (2009)] and the recent theoretical calculations by Cheng et al. [J. Phys. Chem. A 113, 13779 (2009)]. A reduced-dimensionality nuclear Hamiltonian was used to compute the ionization dynamics for both the ground state and first excited state of the cation. The dynamics show markedly different behavior and spectroscopic signatures depending on which state of the cation is accessed by the ionization. Ionization to the ground state cation surface induces a hydrogen transfer which is complete within 50 fs, whereas ionization to the first excited state results in a much slower process.


Phylogenomics reveals a new 'megagroup' including most photosynthetic eukaryotes.
Advances in molecular phylogeny of eukaryotes have suggested a tree composed of a small number of supergroups. Phylogenomics recently established the relationships between some of these large assemblages, yet the deepest nodes are still unresolved. Here, we investigate early evolution among the major eukaryotic supergroups using the broadest multigene dataset to date (65 species, 135 genes). Our analyses provide strong support for the clustering of plants, chromalveolates, rhizarians, haptophytes and cryptomonads, thus linking nearly all photosynthetic lineages and raising the question of a possible unique origin of plastids. At its deepest level, the tree of eukaryotes now receives strong support for two monophyletic megagroups comprising most of the eukaryotic diversity.


Dissecting first-year students' perceptions of health profession groups: potential barriers to interprofessional education.
Previous research has shown that health profession students enter interprofessional education (IPE) programs with negative perceptions of health disciplines other than their own, which could serve as possible barriers to engagement with interprofessional principles. Yet, past studies have not fully dissected these perceptions, nor have they examined how these perceptions may contrast with how students view their own future profession. A total of 638 students from six different health profession training programs completed surveys assessing their perceptions/stereotypes of their own and other health professions. ANOVA and MANCOVA analyses showed a high degree of variability in how each profession is perceived by the students, but that the students, regardless of discipline (except medical students), rated their own profession the highest on almost every attribute listed. The data provide evidence for the tenets of Social Identity Theory raised in the relevant literature. The authors also suggest that the lack of adequately formulated "professional-in-training" identity, as well as the formidability of anticipatory socialization, help to foster and perpetuate these stereotypes and that IPE programs have the potential to exacerbate these negative perceptions.


Stress reduction through mindfulness meditation. Effects on psychological symptomatology, sense of control, and spiritual experiences.
This study examined the effects of an 8-week stress reduction program based on training in mindfulness meditation. Previous research efforts suggesting this program may be beneficial in terms of reducing stress-related symptomatology and helping patients cope with chronic pain have been limited by a lack of adequate comparison control group. Twenty-eight individuals who volunteered to participate in the present study were randomized into either an experimental group or a nonintervention control group. Following participation, experimental subjects, when compared with controls, evidenced significantly greater changes in terms of: (1) reductions in overall psychological symptomatology; (2) increase in overall domain-specific sense of control and utilization of an accepting or yielding mode of control in their lives, and (3) higher scores on a measure of spiritual experiences. The techniques of mindfulness meditation, with their emphasis on developing detached observation and awareness of the contents of consciousness, may represent a powerful cognitive behavioral coping strategy for transforming the ways in which we respond to life events. They may also have potential for relapse prevention in affective disorders.


Educational inequalities in disability linked to social security coverage among older individuals in five Latin American countries.
Although Latin American populations are ageing rapidly, many countries have important shortcomings in terms of access to social security coverage. Despite significant improvements regarding access to healthcare, the coverage gap in terms of pensions represents a major challenge for public health and equity in the region. The principal aim of this study was to systematically assess the association between social security coverage and disability among older individuals in five Latin American countries, as well as the extent of existing inequalities and its determinants. To do so we use cross-sectional and comparative data for individuals aged 60 and older in Chile, Colombia, El Salvador, Paraguay and Uruguay from the Longitudinal Social Protection Survey (ELPS). We used multivariate regression to assess the association between disability and healthcare as well as pension coverage. Concentration indices (CI) and an Oaxaca-Blinder decomposition approach were used to assess overall inequalities in disability according to education as well as their components. With the exception of El Salvador, we find significant inequalities in disability disfavoring lower educated individuals. With regards to healthcare, we find no significant association of healthcare coverage with disability in any of the five countries, nor does it explain educational inequalities in disability. However, pension access was associated with lower risks of disability in Chile, Colombia, Paraguay and Uruguay, and explains a substantial share of educational inequality in Chile, Colombia and Paraguay. Whereas significant changes have already been made regarding universal healthcare coverage, the results suggest that expanding access to pensions may not only lead to improvements in health among older individuals in the region, but also substantially reduce socio-economic inequalities in health and successful ageing.


Multiple types of child maltreatment and adolescent mental health in Viet Nam.
To examine the prevalence of multiple types of maltreatment (MTM), potentially confounding factors and associations with depression, anxiety and self-esteem among adolescents in Viet Nam. In 2006 we conducted a cross-sectional survey of 2591 students (aged 12-18 years; 52.1% female) from randomly-selected classes in eight secondary schools in urban (Hanoi) and rural (Hai Duong) areas of northern Viet Nam (response rate, 94.7%). Sequential multiple regression analyses were performed to estimate the relative influence of individual, family and social characteristics and of eight types of maltreatment, including physical, emotional and sexual abuse and physical or emotional neglect, on adolescent mental health. Females reported more neglect and emotional abuse, whereas males reported more physical abuse, but no statistically significant difference was found between genders in the prevalence of sexual abuse. Adolescents were classified as having nil (32.6%), one (25.9%), two (20.7%), three (14.5%) or all four (6.3%) maltreatment types. Linear bivariate associations between MTM and depression, anxiety and low self-esteem were observed. After controlling for demographic and family factors, MTM showed significant independent effects. The proportions of the variance explained by the models ranged from 21% to 28%. The combined influence of adverse individual and family background factors and of child maltreatment upon mental health in adolescents in Viet Nam is consistent with research in non-Asian countries. Emotional abuse was strongly associated with each health indicator. In Asian communities where child abuse is often construed as severe physical violence, it is important to emphasize the equally pernicious effects of emotional maltreatment.


Variation in DNA repair genes ERCC2, XRCC1, and XRCC3 and risk of follicular lymphoma.
The reasons for the positive association between skin cancer and non-Hodgkin's lymphoma are not known but may be due to common susceptibility involving suboptimal DNA repair. Therefore, we investigated selected polymorphisms and haplotypes in three DNA repair genes, previously associated with skin cancer and DNA repair capacity, in risk of follicular lymphoma, including possible gene interaction with cigarette smoking and sun exposure. We genotyped 19 single nucleotide polymorphisms (SNP) in the ERCC2, XRCC1, and XRCC3 genes in 430 follicular lymphoma patients and 605 controls within a population-based case-control study in Denmark and Sweden. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using unconditional logistic regression and haplotype associations were assessed with a global score test. We observed no associations between variation in the ERCC2 and XRCC1 genes and follicular lymphoma risk. In XRCC3, increased risk of follicular lymphoma was suggested for rare homozygotes of three SNPs [Rs3212024: OR, 1.8 (95% CI, 1.1-2.8); Rs3212038: OR, 1.5 (95% CI, 1.0-2.4); Rs3212090: OR, 1.5 (95% CI, 1.0-2.5)]. These results were strengthened in current cigarette smokers. However, evidence of differences in XRCC3 haplotype distributions between follicular lymphoma cases and controls was weak, both overall and in current smokers. We conclude that polymorphic variation in the XRCC3 gene, but not in ERCC2 or XRCC1, may be of importance for susceptibility to follicular lymphoma, perhaps primarily in current smokers. The link between skin cancer and follicular lymphoma is unlikely to be mediated through common variation in the studied DNA repair gene polymorphisms.


Could vitamin D reduce obesity-associated inflammation? Observational and Mendelian randomization study.
Obesity is associated with inflammation but the role of vitamin D in this process is not clear. We aimed to assess the associations between serum 25-hydroxyvitamin D [25(OH)D], BMI, and 16 inflammatory biomarkers, and to assess the role of vitamin D as a potential mediator in the association between higher BMI and inflammation. Northern Finland Birth Cohort 1966 (NFBC1966) 31-y data on 3586 individuals were analyzed to examine the observational associations between BMI, 25(OH)D, and 16 inflammatory biomarkers. Multivariable regression analyses and 2-sample regression-based Mendelian randomization (MR) mediation analysis were performed to assess any role of vitamin D in mediating a causal effect of BMI on inflammatory biomarkers [soluble intercellular adhesion molecule 1 (sICAM-1), high sensitivity C-reactive protein (hs-CRP), and α1-acid glycoprotein (AGP)] for which observational associations were detected. For MR, genome-wide association study summary results ranging from 5163 to 806,834 individuals were used for biomarkers, 25(OH)D, and BMI. Findings were triangulated with a literature review of vitamin D supplementation trials. In NFBC1966, mean BMI (kg/m2) was 24.8 (95% CI: 24.7, 25.0) and mean 25(OH)D was 50.3 nmol/L (95% CI: 49.8, 50.7 nmol/L). Inflammatory biomarkers correlated as 4 independent clusters: interleukins, adhesion molecules, acute-phase proteins, and chemokines. BMI was positively associated with 9 inflammatory biomarkers and inversely with 25(OH)D (false discovery rate < 0.05). 25(OH)D was inversely associated with sICAM-1, hs-CRP, and AGP, which were positively associated with BMI. The MR analyses showed causal association of BMI on these 3 inflammatory biomarkers. There was no observational or MR evidence that circulating 25(OH)D concentrations mediated the association between BMI and these 3 inflammatory markers. Review of randomized controlled trials (RCTs) supported our findings showing no impact of vitamin D supplementation on inflammatory biomarkers. The findings from our observational study and causal MR analyses, together with data from RCTs, do not support a beneficial role of vitamin D supplementation on obesity-related inflammation.


Functional analysis of the internal translation initiation site of foot-and-mouth disease virus.
Mutagenesis of the large untranslated sequence at the 5' end of the genome of foot-and-mouth disease virus revealed that a region of approximately 450 nucleotides preceding the open reading frame of the viral polyprotein is involved in the regulation of translation initiation at two internal start sites. Variations in two domains of this region reduced the translation efficiency up to 10-fold, whereas an intermediate segment seemed to be less essential. A pyrimidine-rich sequence preceding the start codon was most sensitive in that conversion of single pyrimidine residues to purines decreased the translation efficiency strongly. The data are in agreement with a recently proposed general structural model for the internal ribosome entry site of the cardiovirusaphthovirus subgroup of picornaviruses (E. V. Pilipenko, V. M. Blinov, B. K. Chernov, T. M. Dmitrieva, and V. I. Agol, Nucleic Acids Res. 17:5701-5711, 1989). They suggest, however, that this model represents only a core structure for the internal entry of ribosomes and that foot-and-mouth disease virus and other members of the picornaviruses need additional regulatory RNA elements for efficient translation initiation.


"A man's gonna do what a man wants to do": African American and Hispanic women's perceptions about heterosexual relationships: a qualitative study.
HIV prevention efforts have given limited attention to the relational schemas and scripts of adult heterosexual women. These broader schemas and scripts of romantic and other sexual liaisons, partner selection, relationship dynamics, and power negotiations may help to better understand facilitators and barriers to HIV risk-reduction practices. We conducted exploratory qualitative interviews with 60 HIV-uninfected heterosexual African-American women from rural counties in North Carolina and Alabama, and Hispanic women from an urban county in southern Florida. Data were collected for relationship expectations; relationship experiences, and relationship power and decision-making. Interview transcripts underwent computer-assisted thematic analysis. Participants had a median age of 34 years (range 18-59), 34% were married or living as married, 39% earned an annual income of $12,000 or less, 12% held less than a high school education, and 54% were employed. Among the Hispanic women, 95% were foreign born. We identified two overarching relationship themes: contradictions between relationship expectations and desires and life circumstances that negated such ideals, and relationship challenges. Within the contradictions theme, we discovered six subthemes: a good man is hard to find; sex can be currency used to secure desired outcomes; compromises and allowances for cheating, irresponsible, and disrespectful behavior; redefining dating; sex just happens; needing relationship validation. The challenges theme centered on two subthemes: uncertainties and miscommunication, and relationship power negotiation. Gender differences in relationship intentions and desires as well as communication styles, the importance of emotional and financial support, and the potential for relationships to provide disappointment were present in all subthemes. In examining HIV risk perceptions, participants largely held that risk for HIV-infection and the need to take precautions were problems of women who differed from them (i.e., abuse drugs, are promiscuous, exchange sex). Underlying women's relational schemas was a belief that relationship priorities differed for men and women. Consequently, expectations and allowances for partner infidelity and negligent behaviors were incorporated into their scripts. Moreover, scripts endorsed women's use of sex as currency in relationship formation and endurance, and did not emphasize HIV risk. Both couple- and gender-specific group-level interventions are needed to deconstruct (breakdown) and reconstruct (rewrite) relationship scripts.


Let it be: mindful acceptance down-regulates pain and negative emotion.
Mindfulness training ameliorates clinical and self-report measures of depression and chronic pain, but its use as an emotion regulation strategy-in individuals who do not meditate-remains understudied. As such, whether it (i) down-regulates early affective brain processes or (ii) depends on cognitive control systems remains unclear. We exposed meditation-naïve participants to two kinds of stimuli: negative vs. neutral images and painful vs. warm temperatures. On alternating blocks, we asked participants to either react naturally or exercise mindful acceptance. Emotion regulation using mindful acceptance was associated with reductions in reported pain and negative affect, reduced amygdala responses to negative images and reduced heat-evoked responses in medial and lateral pain systems. Critically, mindful acceptance significantly reduced activity in a distributed, a priori neurologic signature that is sensitive and specific to experimentally induced pain. In addition, these changes occurred in the absence of detectable increases in prefrontal control systems. The findings support the idea that momentary mindful acceptance regulates emotional intensity by changing initial appraisals of the affective significance of stimuli, which has consequences for clinical treatment of pain and emotion.


Femtosecond direct-written integrated mode couplers.
We report the design and fabrication of three-dimensional integrated mode couplers operating in the C-band. These mode-selective couplers were inscribed into a boro-aluminosilicate photonic chip using the femtosecond laser direct-write technique. Horizontally and vertically written two-core couplers are shown to allow for the multiplexing of the LP11a and LP11b spatial modes of an optical fiber, respectively, with excellent mode extinction ratios (25-37 + dB) and low loss (~1 dB) between 1500 and 1580 nm. Furthermore, optimized fabrication parameters enable coupling ratios close to 100%. When written in sequence, the couplers allow for the multiplexing of all LP01, LP11a and LP11b modes. This is also shown to be possible using a single 3-dimensional three-core coupler. These integrated mode couplers have considerable potential to be used in mode-division multiplexing for increasing optical fiber capacity. The three-dimensional capability of the femtosecond direct-write technique provides the versatility to write linear cascades of such two- and three-core couplers into a single compact glass chip, with arbitrary routing of waveguides to ensure a small footprint. This technology could be used for high-performance, compact and cost-effective multiplexing of large numbers of modes of an optical fiber.


Remineralisation by chewing sugar-free gums in a randomised, controlled in situ trial including dietary intake and gauze to promote plaque formation.
Remineralisation has been shown to be an effective mechanism of preventing the progression of enamel caries. The aim of this double-blind, randomised, cross-over in situ study was to compare enamel remineralisation by chewing sugar-free gum with or without casein phosphopeptide amorphous calcium phosphate (CPP-ACP) where the enamel lesions were exposed to dietary intake and some were covered with gauze to promote plaque formation. Participants wore removable palatal appliances containing 3 recessed enamel half-slabs with subsurface lesions covered with gauze and 3 without gauze. Mineral content was measured by transverse microradiography, and plaque composition was analysed by real-time polymerase chain reaction. For both the gauze-free and gauze-covered lesions, the greatest amount of remineralisation was produced by the CPP-ACP sugar-free gum, followed by the gum without CPP-ACP and then the no-gum control. Recessing the enamel in the appliance allowed plaque accumulation without the need for gauze. There was a trend of less remineralisation and greater variation in mineral content for the gauze-covered lesions. The cell numbers of total bacteria and streptococci were slightly higher in the plaque from the gauze-covered enamel for 2 of the 3 treatment legs; however, there was no significant difference in Streptococcus mutans cell numbers. In conclusion, chewing sugar-free gum containing CPP-ACP promoted greater levels of remineralisation than a sugar-free gum without CPP-ACP or a no-gum control using an in situ remineralisation model including dietary intake irrespective of whether gauze was used to promote plaque formation or not.


Importance of adult literacy in understanding health disparities.
In several recent studies, the importance of education and race in explaining health-related disparities has diminished when literacy was considered. This relationship has not been tested in a nationally representative sample of U.S. adults. To understand the effect of adult literacy on the explanatory power of education and race in predicting health status among U.S. adults. Using the 1992 National Adult Literacy Survey, logistic regression models predicting health status were estimated with and without literacy to test the effect of literacy inclusion on race and education. A nationally representative sample of 23,889 noninstitutionalized U.S. adults. Poor health status was measured by having a work-impairing condition or a long-term illness. Literacy was measured by an extensive functional skills test. When literacy was not considered, African Americans were 1.54 (95% confidence interval, 1.29 to 1.84) times more likely to have a work-impairing condition than whites, and completion of an additional level of education made one 0.75 (0.69 to 0.82) times as likely to have a work-impairing condition. When literacy was considered, the effect estimates of both African-American race and education diminished 32% to the point that they were no longer significantly associated with having a work-impairing condition. Similar results were seen with long-term illness. The inclusion of adult literacy reduces the explanatory power of crucial variables in health disparities research. Literacy inequity may be an important factor in health disparities, and a powerful avenue for alleviation efforts, which has been mistakenly attributed to other factors.


Essential Metals Zinc, Selenium, and Strontium Protect against Chromosome Damage Caused by Polycyclic Aromatic Hydrocarbons Exposure.
Essential metals play important roles in maintaining cellular homeostasis, but the effects of their interaction with the environmental pollutants are still not very well-known in human subjects. The aim of this study was to evaluate the roles of essential metals and their interactions with polycyclic aromatic hydrocarbons (PAHs) on chromosome damage, an early carcinogenic event. A total of 1245 male workers were included in this study and the levels of 11 urinary essential metals, 12 urinary PAH metabolites, plasma concentrations of benzo[a]pyrene-r-7,t-8,t-9,c-10-tetrahydotetrol-albumin (BPDE-Alb) adducts, and lymphocyte micronucleus (MN) frequencies were monitored. We found that zinc (Zn), selenium (Se), and strontium (Sr) have significant inverse dose-response relationships with MN frequencies (all P < 0.05). Furthermore, the protective roles of Zn, Se, and Sr were mainly shown among subjects with high levels of BPDE-Alb adducts. Significant effect modification of BPDE-Alb adducts on the associations of Zn, Se, and Sr with MN frequencies was observed (all Pinteraction < 0.05). Our study showed evidence that Zn, Se, and Sr play protective roles in reducing chromosome damage, and these effects can be modified by PAH exposure levels. These findings add potential evidence for the preventive effects of Zn, Se, and Sr against carcinogenesis in human subjects.


Amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with evidence of both anterior horn cell and corticospinal tract degeneration. The incidence of ALS is 1 to 2.5 cases per 100,000 population and the disease occurs primarily in adult life. The etiology of sporadic ALS remains unknown, although 5 to 10% of cases are familial. The diagnosis of ALS requires the presence of both upper and lower motor neuron findings and progressive motor dysfunction. Several theories regarding the pathogenesis of ALS have emerged including glutamate excitotoxicity, free radical oxidative stress, neurofilament accumulation, and autoimmunity. Clinical trials involving antiglutamate agents, antioxidants, immunosuppressants, and growth factors have shown no substantial benefit in slowing progression, with death usually occurring 2 to 5 years following the onset of symptoms. The management of ALS patients requires a multidisciplinary team that can provide the numerous medical and physical interventions necessary to treat weakness and fatigue, bulbar dysfunction, spasticity and pain, depression, and respiratory failure.


Job Demand-Control-Support Model as Related to Objectively Measured Physical Activity and Sedentary Time in Working Women and Men.
A physically active lifestyle incurs health benefits and physically active individuals show reduced reactivity to psychosocial stressors. However, the findings are inconclusive and are based on self-reported physical activity and sedentary time. The present study aimed at studying the associations between psychological stressors (job demand, control, support, JD-C-S) and objectively measured physical activity (PA) on various intensities from sedentary (SED) to vigorous physical activity. The participants were 314 employees from a cross-sectional study. PA data were collected with the accelerometer ActiGraph GT3X (Pensacola, FL, USA), SED data with the inclinometer activPAL (PAL Technologies Ltd., Glasgow, Scotland, UK), and psychosocial stressors with a web questionnaire. Results showed that vigorous-intensity PA was negatively associated with demand (β -0.15, p < 0.05), even when adjusted for the covariates. SED was negatively associated to support (β -0.13, p < 0.05). Stress significantly moderated relations between support and sedentary time (β -0.12, p < 0.05). Moderate PA (MVPA) was negatively associated with demand, but only when controlling for overtime (β -0.13, p < 0.05). MVPA was also negatively associated with control (β -0.15, p < 0.05) but not when work engagement was included in the model. Being more physically active and spending less time sedentary may help to handle job situations with high demand and low support.


Two pathways converge at CED-10 to mediate actin rearrangement and corpse removal in C. elegans.
The removal of apoptotic cells is essential for the physiological well being of the organism. In Caenorhabditis elegans, two conserved, partially redundant genetic pathways regulate this process. In the first pathway, the proteins CED-2, CED-5 and CED-12 (mammalian homologues CrkII, Dock180 and ELMO, respectively) function to activate CED-10 (Rac1). In the second group, the candidate receptor CED-1 (CD91/LRP/SREC) probably recognizes an unknown ligand on the apoptotic cell and signals via its cytoplasmic tail to the adaptor protein CED-6 (hCED-6/GULP), whereas CED-7 (ABCA1) is thought to play a role in membrane dynamics. Molecular understanding of how the second pathway promotes engulfment of the apoptotic cell is lacking. Here, we show that CED-1, CED-6 and CED-7 are required for actin reorganization around the apoptotic cell corpse, and that CED-1 and CED-6 colocalize with each other and with actin around the dead cell. Furthermore, we find that the CED-10(Rac) GTPase acts genetically downstream of these proteins to mediate corpse removal, functionally linking the two engulfment pathways and identifying the CED-1, -6 and -7 signalling module as upstream regulators of Rac activation.


Ketamine as treatment for post-traumatic stress disorder: a review.
Post-traumatic stress disorder (PTSD) continues to make headlines given multiple military engagements across the world and civilian traumas, and resultant PTSD development continues at an even pace. Currently, antidepressant and cognitive-behavioral therapy have the greatest evidence base but still do not yield a remission of PTSD symptoms in many patients. Off-label and novel treatments continue to be considered for more refractory and disabling cases of PTSD. Ketamine is one such treatment that has been discussed and utilized more often for treatment-resistant major depressive disorder (MDD). Its mechanism is controversial regarding its potential to create anxiety, but the perceived benefit of a rapid reduction of symptoms makes it worthy for study in animal models of, and possibly human studies in, PTSD. The current literature and theoretical mechanism of action is discussed in this manuscript.


Search for heavy neutrinos and right-handed W bosons in events with two leptons and jets in pp collisions at [Formula: see text] with the ATLAS detector.
This letter reports on a search for hypothetical heavy neutrinos, N, and right-handed gauge bosons, WR, in events with high transverse momentum objects which include two reconstructed leptons and at least one hadronic jet. The results were obtained from data corresponding to an integrated luminosity of 2.1 fb-1 collected in proton-proton collisions at [Formula: see text] with the ATLAS detector at the CERN Large Hadron Collider. No excess above the Standard Model background expectation is observed. Excluded mass regions for Majorana and Dirac neutrinos are presented using two approaches for interactions that violate lepton and lepton-flavor numbers. One approach uses an effective operator framework, the other approach is guided by the Left-Right Symmetric Model. The results described in this letter represent the most stringent limits to date on the masses of heavy neutrinos and WR bosons obtained in direct searches.


A randomized clinical trial of a group cognitive-behavioral therapy to reduce alcohol use among human immunodeficiency virus-infected outpatients in western Kenya.
Culturally relevant and feasible interventions are needed to address limited professional resources in sub-Saharan Africa for behaviorally treating the dual epidemics of HIV and alcohol use disorder. This study tested the efficacy of a cognitive-behavioral therapy (CBT) intervention to reduce alcohol use among HIV-infected outpatients in Eldoret, Kenya. Randomized clinical trial. A large HIV outpatient clinic in Eldoret, Kenya, affiliated with the Academic Model Providing Access to Healthcare collaboration. A total of 614 HIV-infected outpatients [312 CBT; 302 healthy life-styles (HL); 48.5% male; mean age: 38.9 years; mean education 7.7 years] who reported a minimum of hazardous or binge drinking. A culturally adapted six-session gender-stratified group CBT intervention compared with HL education, each delivered by paraprofessionals over six weekly 90-minute sessions with a 9-month follow-up. Primary outcome measures were percentage of drinking days (PDD) and mean drinks per drinking day (DDD) computed from retrospective daily number of drinks data obtained by use of the time-line follow-back from baseline to 9 months post-intervention. Exploratory analyses examined unprotected sex and number of partners. Median attendance was six sessions across condition. Retention at 9 months post-intervention was high and similar by condition: CBT 86% and HL 83%. PDD and DDD marginal means were significantly lower in CBT than HL at all three study phases. Maintenance period, PDD - CBT = 3.64 (0.696), HL = 5.72 (0.71), mean difference 2.08, 95% confidence interval (CI) = 0.13 - 4.04; DDD - CBT = 0.66 (0.96), HL = 0.98 (0.098), mean difference = 0.31, 95% CI = 0.05 - 0.58. Risky sex decreased over time in both conditions, with a temporary effect for CBT at the 1-month follow-up. A cognitive-behavioral therapy intervention was more efficacious than healthy lifestyles education in reducing alcohol use among HIV-infected Kenyan outpatient drinkers.


Endothelial cells augment T cell interleukin 2 production by a contact-dependent mechanism involving CD2/LFA-3 interaction.
We have demonstrated that endothelial cells (EC) augment IL-2 production by PHA-stimulated PBMC or purified CD4+ T cells and that the increase is apparent both in the amount of soluble IL-2 secreted and in the level of specific mRNA detectable by Northern blot hybridization. The ability of EC to affect levels of IL-2 cannot be reproduced by soluble factors, including the cytokines IL-1, IL-6, IFN-gamma, or TNF, conditioned medium from resting EC or IL-1, IFN-gamma- or TNF-treated EC, or from resting PBMC + EC cultures. Separation of the EC and PBMC by a Transwell membrane demonstrated that cell contact was required for augmentation of IL-2 synthesis and that this effect was unlikely to be mediated by a short-lived soluble signal. The cell-cell interaction required the ligand pair CD2/LFA-3, since augmentation could be inhibited by antibodies to these structures. Antibodies to ICAM-1, LFA-1, CD4, and MHC class II were without effect. A contact-dependent pathway involving CD2/LFA-3 interactions also may be used by EC to augment IL-2 production from T cells stimulated more specifically through the TCR/CD3 complex with antibody OKT3. This pathway provides a proliferative advantage to T cells stimulated with OKT3 in the presence of EC and may also be involved in the proliferative response of resting T cells to allogeneic class II MHC-expressing EC. We propose that EC augmentation of T cell IL-2 synthesis may be critical in the ability of EC to elicit primary T cell antigen responses and may have consequences for the development of localized cell-mediated immune reactions.


A study of synthetic approaches to 2-acyl DHA lysophosphatidic acid.
Lysophosphatidic acid (LPA) is a chemical mediator with a very simple glycerophospholipid structure. 1-Acyl LPA and 2-acyl LPA are biosynthesized in vivo. Unlike 1-acyl LPA, the biological function of 2-acyl LPA has been hardly elucidated and even organic synthesis of 2-acyl LPA had not been established. We suppressed acyl migration by formation of a salt with a phosphate group in order to synthesize 2-acyl LPA condensed with docosahexaenoic acid.


Two Distinct Isolates of Tomato yellow leaf curl virus Threaten Tomato Production in Arizona and Sonora, Mexico.
Severe yellow leaf curl and plant stunting symptoms were observed in tomato plants from two home gardens in central Arizona (Phoenix area) and a tomato field in Sonora, Mexico during the fall of 2006. Disease symptoms were reminiscent of those reported in Florida during 1994 (4) and more recently in tomato fields in the Pacific Coast state of Sinaloa, Mexico found to be infected with the exotic Tomato yellow leaf curl virus (TYLCV) (2). Total DNA was extracted from two symptomatic tomato plants from Arizona and Sonora and used as a template in PCR. PCR products of the core region of the begomovirus coat protein gene (Cp) were cloned (n = 3) and the DNA sequence was determined. BLAST analysis of the 579 bases with sequences available in the NCBI GenBank database indicated the closest match was to an isolate of the monopartite begomovirus TYLCV from Israel, which was known to have been introduced into the Caribbean region, including Puerto Rico, the southeastern United States, and Mexico from 1990 to 1996 (1,4). The full-length TYLCV genome (approximately 2,800 bases) was amplified for a field isolate from each location by rolling circle amplification (RCA) using TempliPhi (Amersham Biosciences, Piscataway, NJ). RCA products were cloned into the plasmid vector pGEM7 (Promega, Madison, WI) that had been previously digested with SacI endonuclease. The complete TYLCV genome sequence was determined for six clones from each RCA product. Nucleotide analysis indicated that the complete TYLCV genome sequences from Sonora and Arizona, respectively, shared 97.6 and 97.7% nt identity. The comparative sequence analysis indicated that TYLCV-Sonora (TYLCV-Son) (GenBank Accession No. EF210555) was 99.1% nt identical to TYLCV reported recently from Culiacan, Mexico (GenBank Accession No. DQ631892). In contrast, TYLCV-AZ (GenBank Accession No. EF210554) shared 99.3% identity with an isolate from Texas, TYLCV-TX (GenBank Accession No. EF110890) (3). Interestingly, the TX and AZ TYLCV isolates contained a unique 29-nt deletion in the intergenic region (IR) between the TATA-box and the nonanucleotide, initiating at nt coordinate 2696. Except for the deletion in the IR region of the AZ and TX isolates, these viruses shared 97.6 to 99.1% nt identity to other TYLCV isolates reported in the Western Hemisphere. The genome sequence for TYLCV-Son shares high nt identity with TYLCV isolates identified in the Yucatan Peninsula and Pacific Coast of Mexico (2), the Caribbean region, and the southeastern United States, suggesting that a single TYLCV species was introduced and has spread throughout North America and the Caribbean (4). The absence of other TYLCV isolates in the Western Hemisphere with the novel 29-nt deletion noted for the TX and AZ isolates suggests that the latter two isolates originated from the same U.S. source. In Mexico, TYLCV was first introduced in the east coast and Yucatan region approximately in 1996. From there, this isolate has spread to the western part of the country (Sinaloa and Sonora) from 2004 to 2006 (2). Similarly, in the United States, TYLCV was introduced and spread in the eastern U.S. states beginning in 1994 (4), where it had been confined until it was discovered in Texas (3) and now Arizona during 2006. References: (1) J. Bird et al. Plant Dis. 85:1028, 2001. (2) J. K. Brown and A. M. Idris. Plant Dis. 90:1360, 2006. (3) T. Isakeit et al. Plant Dis. 91:466, 2007. (4) J. E. Polston et al. Plant Dis. 78:831, 1994.


When it is better to estimate a slope with only one point.
When investigating the change in a biomarker, it is often believed that at least two measurements are needed from each participant, and that those with only one measurement should be excluded. In this short note, we explain why this could lead to imprecise and biased estimates. Furthermore, we discuss a standard statistical method that handles such issues.


The health of single mothers and fathers in Germany.
In every fifth family in Germany, one parent lives alone with children in the household. Life as a single parent is often marked by challenges that include adopting sole responsibility for the child's education and care, alongside employment commitments, and the difficulties of reconciling work and family life. Moreover, despite comparatively high employment rates, single parents - and their children - are greatly affected by poverty. This paper compares the health of single parents and parents living in partnership and analyses the extent to which single parents' health varies according to their socio-economic and employment status, and social support. The analysis was conducted using data from the German Health Update (GEDA) study in 2009, 2010 and 2012 on fair or poor self-rated general health, as well as depression, back pain, obesity, smoking, sporting inactivity and the non-utilization of dental check-ups. The analyses are based on data from 9,806 women and 6,279 men living in a household with at least one child under the age of 18. The study identified a significantly higher prevalence for all health indicators (apart from obesity) among single mothers compared to mothers living with a partner. In the case of single fathers, higher prevalences were found for depression, smoking and the non-utilization of dental check-ups. On average, the lower socio-economic status of women can explain a certain proportion of the health impairment of single parents, but not for men. However, a lower socio-economic status or social support do not account for the health impairments of single parents. Therefore, the higher prevalence of health impairments among single parents cannot simply be attributed to differences in employment status or to lower levels of social support; rather, certain health indicators show a cumulative effect between single-parents status and the social factors mentioned above. The results presented here provide a differentiated view of the relationship between the health and social situation of single parents. Improving the financial position of one-parent families and making it easier to reconcile work and family life are important steps that would help improve the health of single parents.


Welsh Primary Schoolchildren's Perceptions of Electronic Cigarettes: A Mixed Methods Study.
There are concerns that the growing popularity of e-cigarettes promotes experimentation among children. Given the influence of the early years on attitude and habit formation, better understanding of how younger children perceive vaping before experimentation begins is needed, to prevent uptake and inform tobacco control strategies. We explored Welsh primary schoolchildren's (aged 7-11) awareness of e-cigarettes relative to tobacco smoking, their understanding of the perceived risks and benefits and their intentions and beliefs about vaping. Data was collected using a mix of methods in June and July 2017 from 8 purposively selected primary schools across Wales. Four hundred and ninety-five children (52% female) aged 7 years (n = 165), 9 years (n = 185) and 11 years (n = 145) completed a class-administered booklet encompassing a draw and write exercise and survey. Ninety-six children participated in 24 peer discussion groups comprised of 2 boys and 2 girls from each year group. Data were analysed independently and findings triangulated. Survey analyses used frequencies, descriptive statistics and chi-squared tests. Content analysis was undertaken on the draw and write data and peer discussion groups were analysed thematically. Study findings highlight that primary schoolchildren have general awareness of e-cigarettes. Vaping was perceived to be healthier than smoking and there was some recognition that e-cigarettes were used for smoking cessation. Understanding of any health harms was limited. Few children intended to smoke or vape in the future but almost half thought it was okay for grownups. Children's perceptions were influenced by exposure through family and friends. Findings suggest a need for e-cigarette education in primary schools, to highlight the associated risks of e-cigarette experimentation including the potential for tobacco initiation.