The global impact of glaucoma.
Although glaucoma is a major global cause of blindness, the lack of a uniform definition of the disease in its different forms makes it difficult to assess its public health impact. By considering the common features of glaucoma, we have analysed available data on the three main forms of the disease: congenital/hereditary glaucoma, primary open-angle, and primary angle-closure glaucoma. A simple model was then developed to estimate the extent of glaucoma on a regional basis, taking into account demographic data, e.g., age distribution, gender and ethnic groups. Overall, the results demonstrate that glaucoma is responsible for approximately 5.2 million blind (15% of the total burden of world blindness).


Fossil gaps inferred from phylogenies alter the apparent nature of diversification in dragonflies and their relatives.
The fossil record has suggested that clade growth may differ in marine and terrestrial taxa, supporting equilibrial models in the former and expansionist models in the latter. However, incomplete sampling may bias findings based on fossil data alone. To attempt to correct for such bias, we assemble phylogenetic supertrees on one of the oldest clades of insects, the Odonatoidea (dragonflies, damselflies and their extinct relatives), using MRP and MRC. We use the trees to determine when, and in what clades, changes in taxonomic richness have occurred. We then test whether equilibrial or expansionist models are supported by fossil data alone, and whether findings differ when phylogenetic information is used to infer gaps in the fossil record. There is broad agreement in family-level relationships between both supertrees, though with some uncertainty along the backbone of the tree regarding dragonflies (Anisoptera). "Anisozygoptera" are shown to be paraphyletic when fossil information is taken into account. In both trees, decreases in net diversification are associated with species-poor extant families (Neopetaliidae, Hemiphlebiidae), and an upshift is associated with Calopterygidae + Polythoridae. When ghost ranges are inferred from the fossil record, many families are shown to have much earlier origination dates. In a phylogenetic context, the number of family-level lineages is shown to be up to twice as high as the fossil record alone suggests through the Cretaceous and Cenozoic, and a logistic increase in richness is detected in contrast to an exponential increase indicated by fossils alone. Our analysis supports the notion that taxa, which appear to have diversified exponentially using fossil data, may in fact have diversified more logistically. This in turn suggests that one of the major apparent differences between the marine and terrestrial fossil record may simply be an artifact of incomplete sampling. Our results also support previous notions that adult colouration plays an important role in odonate radiation, and that Anisozygoptera should be grouped in a single inclusive taxon with Anisoptera, separate from Zygoptera.


Recognising facial surfaces.
The extent to which faces depicted as surfaces devoid of pigmentation and with minimal texture cues ('head models') could be matched with photographs (when unfamiliar) and identified (when familiar) was examined in three experiments. The head models were obtained by scanning the three-dimensional surface of the face with a laser, and by displaying the surface measured in this way by using standard computer-aided design techniques. Performance in all tasks was above chance but far from ceiling. Experiment 1 showed that matching of unfamiliar head models with photographs was affected by the resolution with which the surface was displayed, suggesting that subjects based their decisions, at least in part, on three-dimensional surface structure. Matching accuracy was also affected by other factors to do with the view-points shown in the head models and test photographs, and the type of lighting used to portray the head model. In experiment 2 further evidence for the importance of the nature of the illumination used was obtained, and it was found that the addition of a hairstyle (not that of the target face) did not facilitate matching. In experiment 3 identification of the head models by colleagues of the people shown was compared with identification of photographs where the hair was concealed and eyes were closed. Head models were identified less well than these photographs, suggesting that the difficulties in their recognition are not solely due to the lack of hair. Women's heads were disproportionately difficult to recognise from the head models. The results are discussed in terms of their implications for the use of such three-dimensional head models in forensic and surgical applications.


Initial localization of regulatory regions of the cardiac sarcolemmal Na(+)-Ca2+ exchanger.
We have analyzed the regulatory properties of the wild-type cardiac Na(+)-Ca2+ exchanger expressed in Xenopus laevis oocytes using the giant excised patch technique. The exchanger is activated by cytoplasmic application of chymotrypsin and exhibits a number of properties that can be changed or abolished by chymotrypsin treatment, including cytoplasmic Na(+)-dependent inactivation, secondary regulation by free cytoplasmic Ca2+, and inhibition by exchanger inhibitory peptide. Thus, the cloned exchanger expressed in oocytes exhibits regulatory properties similar to those of the native sarcolemmal exchanger. The exchanger protein contains a large (520 amino acids) hydrophilic domain modeled to be intracellular. The role of this region in exchanger function and regulation was examined by deletion mutagenesis. Mutants with residues 240-679 and 562-685 deleted exhibited exchange activity, indicating that this extensive region is not essential for transport function. Both mutants were stimulated by chymotrypsin treatment. Neither mutant demonstrated regulation by free cytoplasmic Ca2+ (Ca2+i) or inhibition by exchanger inhibitory peptide (XIP). However, mutant delta 562-685 but not delta 240-679 displayed Na(+)-dependent inactivation. The data suggest that the binding sites for XIP and regulatory Ca2+ may reside in the region encompassed by residues 562-685. A chimera made from renal and cardiac exchangers has normal regulatory characteristics and helps to further define these sites.


Design of short peptides to block BTLA/HVEM interactions for promoting anticancer T-cell responses.
Antibody based immune-checkpoint blockade therapy is a major breakthrough in oncology, leading to clinical benefit for cancer patients. Among the growing family of inhibitory receptors, the B and T lymphocyte attenuator (BTLA), which interacts with herpes virus entry mediator (HVEM), is a promising target for immunotherapy. Indeed, BTLA inhibits T-cell proliferation and cytokine production. The crystal structure of the BTLA/HVEM complex has shown that the HVEM(26-38) fragment is directly involved in protein binding. We designed and analyzed the capacity of several analogs of this fragment to block the ligation between BTLA and HVEM, using competitive ELISA and cellular assay. We found that the HVEM(23-39) peptide can block BTLA/HVEM ligation. However, the blocking ability was due to the Cys encompassed in this peptide and that even free cysteine targeted the BTLA protein and blocked its interaction with HVEM. These data highlight a Cys-related artefact in vitro, which should be taken in consideration for future development of BTLA/HVEM blocking compounds.


A periodic structure mimics a metamaterial.
We show that properties attributed to planar metamaterials that support resonances due to an appropriately shaped unit cell can also be identified in a medium that exhibits a resonance evoked by its period only. By choosing a subwavelength period, the effective material parameters of such a medium can be retrieved from the complex reflected and transmitted amplitude. The parameters exhibit Lorentzian line shapes in the spectral vicinity of the resonances associated with the period. If this material is stacked to form a three-dimensional medium, a stop gap is observed in transmission in the frequency range where the real part of one effective material parameter becomes negative. The resonance at the origin of the response is related to the excitation of a higher-order Bloch mode. Because their negligible excitation is a prerequisite for deriving effective material parameters, the analyzed structure mimics only the response of a metamaterial but cannot be regarded as a metamaterial.


Toward a Trust Evaluation Mechanism in the Social Internet of Things.
In the blooming era of the Internet of Things (IoT), trust has been accepted as a vital factor for provisioning secure, reliable, seamless communications and services. However, a large number of challenges still remain unsolved due to the ambiguity of the concept of trust as well as the variety of divergent trust models in different contexts. In this research, we augment the trust concept, the trust definition and provide a general conceptual model in the context of the Social IoT (SIoT) environment by breaking down all attributes influencing trust. Then, we propose a trust evaluation model called REK, comprised of the triad of trust indicators (TIs) Reputation, Experience and Knowledge. The REK model covers multi-dimensional aspects of trust by incorporating heterogeneous information from direct observation (as Knowledge TI), personal experiences (as Experience TI) to global opinions (as Reputation TI). The associated evaluation models for the three TIs are also proposed and provisioned. We then come up with an aggregation mechanism for deriving trust values as the final outcome of the REK evaluation model. We believe this article offers better understandings on trust as well as provides several prospective approaches for the trust evaluation in the SIoT environment.


Behçet's disease and genetic interactions between HLA-B*51 and variants in genes of autoinflammatory syndromes.
Behçet's disease (BD) is an immune-mediated systemic disorder with a well-established genetic base. In a previous study, using a next generation sequencing approach, we found many rare variants and some functional polymorphisms in genes related to autoinflammatory syndromes (AID): CECR1, MEFV, MVK, NLRP3, NOD2, PSTPIP1 and TNFRSF1A in our BD cohort. Our strategy did not allow us to establish either number of patients with variants, proportion of individuals accumulating them or relationship with other genetic factors. With the goal to answer these questions, the individual samples were sequenced. Additionally, three functional polymorphisms: NLRP3 p.Gln703Lys, NOD2 p.Arg702Trp and p.Val955Ile were genotyped using TaqMan assays. A total of 98 patients (27.6%) carried at least one rare variant and 13 of them (3.7%) accumulated two or three. Functional regression model analysis suggests epistatic interaction between B51 and MEFV (P = 0.003). A suggestive protective association of the minor allele of NOD2 p.Arg702Trp (P = 0.01) was found in both, B51 positive and negative individuals. Therefore, a high percentage of patients with BD have rare variants in AID genes. Our results suggest that the association of MEFV with BD could be modulated by the HLA molecules; whereas the protective effect of NOD2 p.Arg702Trp would be independent of HLA.


Patterns of viral decline during PEG-interferon alpha-2b therapy in HBeAg-positive chronic hepatitis B: relation to treatment response.
In chronic hepatitis B, it is difficult to predict an early therapeutic response. We investigated the viral decline during therapy with pegylated interferon alpha-2b (PEG-IFN) with or without lamivudine in 266 HBeAg-positive chronic hepatitis B patients. In patients treated with PEG-IFN and lamivudine, a uniform biphasic viral decline pattern was found during therapy and there were no marked differences in viral load between those who lost HBeAg at the end of follow-up (response) or not. In contrast, those treated with PEG-IFN monotherapy exhibited different viral decline patterns. A delayed decline of at least two log from baseline HBV DNA after week 4 but before week 32 was associated with the highest response rate (63%). In comparison, response was 52% for patients with an early decline (week 0-4), 38% for a late decline (week 32-52), 27% for a posttreatment decline (week 52-78) and 11% for patients with no substantial decline. The HBsAg loss was 22% in the delayed decline pattern compared to 4% for those with early decline and none for other decline patterns. In conclusion, different patterns of decline in viral load during treatment with PEG-IFN monotherapy were associated with different rates of HBeAg and HBsAg loss at the end of follow-up. Since there was a considerable response, even in patients with a late or posttreatment decline pattern, prediction of response based on viral decline during the first months of therapy was difficult.


Small-molecule-based inhibition of histone demethylation in cells assessed by quantitative mass spectrometry.
Post-translational modifications on histones are an important mechanism for the regulation of gene expression and are involved in all aspects of cell growth and differentiation, as well as pathological processes including neurodegeneration, autoimmunity, and cancer. A major challenge within the chromatin field is to develop methods for the quantitative analysis of histone modifications. Here we report a mass spectrometry (MS) approach based on ultraperformance liquid chromatography high/low collision switching (UPLC-MS(E)) to monitor histone modifications in cells. This approach is exemplified by the analysis of trimethylated lysine-9 levels in histone H3, following a simple chemical derivatization procedure with d(6)-acetic anhydride. This method was used to study the inhibition of histone demethylases with pyridine-2,4-dicarboxylic acid (PDCA) derivatives in cells. Our results show that the PDCA-dimethyl ester inhibits JMJD2A catalyzed demethylation of lysine-9 on histone H3 in human HEK 293T cells. Demethylase inhibition, as observed by MS analyses, was supported by immunoblotting with modification-specific antibodies. The results demonstrate that PDCA derived small molecules are cell permeable demethylase inhibitors and reveal that quantitative MS is a useful tool for measuring post-translational histone modifications in cells.


Ectopic Pregnancy in Tigray, Ethiopia: A Cross-Sectional Survey of Prevalence, Management Outcomes, and Associated Factors.
Ectopic pregnancy is a neglected and challenging gynecologic problem in developing countries including Ethiopia. The present study is aimed at assessing the prevalence of ectopic pregnancy, its management outcomes, and factors associated with management outcomes in Tigray, North Ethiopia. We employed a four-year retrospective cross-sectional study from September 2015 to August 2019. We extracted data about all pregnant mothers who were admitted and managed for EPs in Axum, Tigray. Ectopic pregnancy and its outcomes (favorable and unfavorable) were the dependent variables, and age, residence, ethnicity, religion, parity, history of abortion, history of EP, pelvic infections, history of surgical procedures, and use contraceptives were the independent variables. We employed descriptive statistics and bivariate and multivariate logistic regression analyses using SPSS. Ethical clearance was obtained from Axum University, Tigray, Ethiopia. The overall prevalence of ectopic pregnancy was 0.52% of total deliveries, which equates to 1 : 193 deliveries. Surgery for ectopic pregnancy accounts for 7.6% of all gynecological surgeries. Most participants were in the age group 26-30 years and lived in rural areas. Among the different EP implantation sites, most cases (92.4%) occurred in the fallopian tube, followed by 5.1% in the ovary and 2.5% in abdominal EPs. Surgical management (laparotomy) was undertaken for all the 79 women diagnosed with EPs, including laparotomy (100%), salpingo-oophorectomy (17.7%), salpingectomy (73.9%), oophorectomy (3.4%), cornual resection (2.5%), and removal of concepts tissue 2.5. The record reports that intraoperative procedure was correctly managed for 47 (59.5%) women but the condition of EP procedure was ruptured for about two-thirds (63.3%) of the women. Thirty (38%) patients had developed some complications after surgery including anemia (hemoglobin < 10.5) (n = 12), fever (n = 10), wound infection (n = 2), and pneumonia (n = 2). Women who were from urban (AOR = 11.2, 95% CI: 2.65-47.2) and who had normal hemoglobin at presentation (AOR = 9.94, 95% CI: 2.03-48.7) were associated with favorable maternal outcomes. More than one-third of women with ectopic pregnancies had an unfavorable maternal outcome, which was higher among rural residents and anemic mothers. Women living in rural areas and anemia during pregnancy should seek special attention in the management of EPs. We also recommend improving the data management of hospitals in Ethiopia.


An elevated free cytosolic Ca2+ wave follows fertilization in eggs of the frog, Xenopus laevis.
The eggs of most or all animals are thought to be activated after fertilization by a transient increase in free cytosolic Ca2+ concentration ([Ca2+]i). We have applied Ca2+-selective microelectrodes to detect such an increase in fertilized eggs of the frog, Xenopus laevis. As observed with an electrode in the animal hemisphere, [Ca2+]i increased from 0.4 to 1.2 microM over the course of 2 min after fertilization, and returned to its original value during the next 10 min. No further changes in [Ca2+]i were detected through the first cleavage division. In eggs impaled with two Ca2+ electrodes, the Ca2+ pulse was observed to travel as a wave from the animal to the vegetal hemisphere, propagating at a rate of approximately 10 microns/s across the animal hemisphere. The apparent delay between the start of the fertilization potential and initiation of the Ca2+ wave at the sperm entry site as approximately 1 min. Through these observations describe only the behavior of subcortical [Ca2+]i, we suggest that our data represent the subcortical extension of the cortical Ca2+ wave thought to trigger cortical granule exocytosis, and we present evidence that both the timing and magnitude of the Ca2+ pulse we observed are consistent with this identity. This first quantification of subcortical [Ca2+]i during fertilization indicates that the Ca2+ transient is available to regulate processes (e.g., protein synthesis) in the subcortical cytosol.


Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines.
The cell line KG1 derived from a patient with erythroleukemia in myeloblastic relapse has the composite phenotype and functional repertoire of myeloblasts. In marked contrast, its subline KG1a has lost myeloid features, acquired new karyotypic markers, and has three characteristics associated with immature T cells: low-level expression of the T cell receptor beta mRNA (but not alpha) transcribed from a germline gene; high-level expression of T3 delta mRNA and intracellular, but not cell surface, T3 protein; and expression of the CD7/gp40 T cell-associated membrane antigen. Both KG1 and KG1a transcribe unrearranged IgH genes. These data suggest that either the KG1 cell line was derived from a common myeloid-lymphoid progenitor or that the KG1a subline phenotype is aberrant.


Depression as a psychosocial consequence of occupational injury in the US working population: findings from the medical expenditure panel survey.
Empirical evidence describing the psychosocial consequences of occupational injury is still limited. The effect of occupational injury on depression might pose unique challenges in workers compared with other kinds of injury. This study aimed to assess the differential impact of workplace injury compared with non-workplace injury on depression over time, and to identify the potential risk factors associated with post-injury depression in the US working population. Using pooled panel data from the Medical Expenditure Panel Survey 2000-2006, a total of 35,155 workers aged 18-64 years who had been followed for about 18 months in each panel were analyzed. Injuries in the 4-5 months before baseline, and subsequent depression incidence during follow-up, were identified using ICD-9 codes for the medical conditions captured in personal interviews. A discrete time-proportional odds model was used. A total of 5.5% of workers with occupational injury at baseline reported depression at follow-up, compared with 4.7% of workers with non-occupational injury and 3.1% of workers without injuries. Those with occupational injuries had more severe injuries and required longer treatment, compared with those with non-occupational injuries. Only 39% of workers with workplace injuries were paid Workers' Compensation (WC). The association between injury and depression appeared to be stronger for workplace injury, and the adjusted odds ratio for depression was 1.72 for those with occupational injury (95% CI: 1.27-2.32), and 1.36 for those with non-occupational injury (95% CI: 1.07-1.65) compared with the no-injury group, after controlling for relevant covariates. Occupational injury was associated with higher odds of developing depression over time. WC as a source of medical payment was associated with 33% higher odds of developing depression (95% CI: 1.01-1.74). Part-time work, shorter job tenure, and long working hours were independently associated with post-injury depression risk. Workers with occupational injury were more likely to become depressed than those with non-occupational injury. The psychosocial consequences of occupational injury, including depression, deserve further exploration to adequately support those injured at work. This finding also emphasizes a need for early intervention to reduce the burden of depression associated with occupational injury.


Increased levels of irisin in people with long-standing Type 1 diabetes.
Irisin stimulates browning of white adipose tissue and improves metabolic control in mice. Betatrophin, another recently described hormone, improves metabolic control in mice by inducing β-cell proliferation. In vitro, irisin stimulates the expression of betatrophin in rat adipocytes. There is a great interest in developing drugs that target or use these hormones for the treatment of obesity and diabetes. We have previously reported on increased levels of betatrophin in people with Type 1 diabetes, but the levels of irisin are currently unknown. To characterize the levels of irisin in Type 1 diabetes and investigate a potential correlation with betatrophin. Irisin and betatrophin were measured by enzyme-linked immunosorbant assay (ELISA) in 45 individuals with Type 1 diabetes and in 25 healthy controls. Irisin levels were increased in people with Type 1 diabetes, and especially in women. Negative correlations between irisin levels and age at onset of Type 1 diabetes and plasma triacylglycerol levels were observed. Interestingly, in women with Type 1 diabetes a negative correlation between irisin and insulin doses was also observed. When computing correlations for all study participants, a positive correlation between irisin and total betatrophin was observed, but not between irisin and full-length betatrophin. We report on increased circulating levels of irisin in people with Type 1 diabetes, especially in women. For women with Type 1 diabetes, the levels of irisin correlated with lower insulin requirements. Further studies are clearly needed to determine the role of irisin in Type 1 diabetes.


Regional hemodynamic effects of antihypertensive renomedullary lipids in conscious rats.
Renomedullary tissue has been proposed to exert an antihypertensive endocrine-like action. The antihypertensive polar renomedullary lipids (APRL) and neutral renomedullary lipids (ANRL) are potential mediators of this action. We evaluated the blood pressure and regional hemodynamic responses to APRL administered peripherally (i.v.) and to the central nervous system (CNS) in normal rats and rats with sinoaortic deafferentation (SAD) to remove baroreflex buffering. Rats were chronically instrumented with Doppler flow probes for measurement of mesenteric, renal, and hind-quarter vascular resistance, with arterial pressure and intravenous catheters, and with lateral cerebroventricular cannuli for intracerebroventricular (i.c.v.) administration. Intravenous APRL (0.01 to 1.0 micrograms) produced a dose-dependent decrease in blood pressure, tachycardia, and dilation of all vascular beds studied. The dose-response relationships were shifted to the left in SAD animals. APRL administered i.c.v. had no effect on intact or SAD rats. Pressor and regional vasoconstrictor responses to norepinephrine, angiotensin, and vasopressin were markedly reduced in SAD animals during constant infusion of APRL. In a second group of conscious SAD animals instrumented for blood pressure and heart rate measurements, intravenous ANRL (500 micrograms) decreased both arterial pressure (-45 +/- 16 mm Hg) and heart rate (-50 +/- 16 bpm). When given i.c.v., however, ANRL (10-100 micrograms) had no significant effect on resting blood pressure or heart rate. These studies suggest that APRL and ANRL produce no significant cardiovascular effects that are mediated through the CNS. However, both lipids are potent depressor agents, and APRL exhibits a strong peripheral vasodilator action and nonspecifically reduces reactivity to vasoconstrictor agents.


Mechanisms shaping fast excitatory postsynaptic currents in the central nervous system.
How different factors contribute to determine the time course of the basic element of fast glutamate-mediated excitatory postsynaptic currents (mEPSCs) in the central nervous system has been a focus of interest of neurobiologists for some years. In spite of intensive investigations, these mechanisms are not well understood. In this review, basic hypotheses are summarized, and a new hypothesis is proposed, which holds that desensitization of AMPA receptors plays a major role in shaping the time course of fast mEPSCs. According to the new hypothesis, desensitization shortens the time course of mEPSCs largely by reducing the buffering of glutamate molecules by AMPA receptors. The hypothesis accounts for numerous findings on fast mEPSCs and is expected to be equally fruitful as a framework for further experimental and theoretical investigations.


Does handwriting on a tablet screen affect students' graphomotor execution? A comparison between Grades Two and Nine.
We sought to ascertain how handwriting with a plastic-tipped pen on the screen of a digital tablet affects graphomotor execution in students, compared with handwriting on paper with a ballpoint pen. We predicted that the modification to propriokinesthetic feedback induced by the screen/plastic tip combination would differently disturb younger and older students, who rely on perceptual feedback either to form letters (former) or to adjust movement execution (latter). Twenty-eight students from Grades Two and Nine were asked to handwrite the alphabet and their names and surnames under the two conditions. Kinematics were recorded using the tablet, controlled by Eye and Pen software. Results showed that handwriting on the tablet surface with a plastic-tipped pen primarily affected pen pauses in the second graders and pen movements in the ninth graders, suggesting a disturbance in segment trajectory calculation in the younger participants and reduced control of muscular adjustment in the older children.


Efficacy and Safety of Flexible Versus Fixed Dosing Intervals of Insulin Glargine 300 U/mL in People with Type 2 Diabetes.
Insulin glargine 300 U/mL (Gla-300) has a more constant and prolonged action profile than insulin glargine 100 U/mL and in clinical studies is associated with similar glycemic control but less hypoglycemia. Whether its effects are altered by variability of injection time was examined in two 3-month substudies. Eligible participants completing 6 months of optimized treatment with Gla-300 in EDITION 1 (n = 109) and EDITION 2 (n = 89), having a mean hemoglobin A1c (HbA1c) level of 7.3 % (SD 1.0 %), were randomized (1:1) to groups advised to increase variability of between-injection intervals to 24 ± up to 3 h or to maintain fixed 24-h intervals for 3 months. Changes of HbA1c level and other efficacy and safety measures were assessed. In the fixed-dosing group, 64% of participants reported all intervals within the 23-25-h range, compared with 15% of those advised flexible dosing. In the fixed- and flexible-dosing groups, 12% and 41%, respectively, of between-injection intervals were outside the 23-25-h range, and 2% and 16%, respectively, were outside the 21-27-h range. Least squares mean between-group difference in HbA1c change from baseline was 0.05 % (95% confidence interval [CI], -0.13 to 0.23); for fasting plasma glucose, 2.7 mg/dL (95% CI, -9.0 to 14.4); and for daily basal insulin dose, 0.00 U/kg (95% CI, -0.02 to 0.03). Frequencies of hypoglycemia and adverse events did not differ between groups. The efficacy and safety of Gla-300 demonstrated in EDITION 1 and EDITION 2 are maintained in substudies when the insulin was injected up to 3 h before or after the usual time of administration.


Refinement of F-actin model against fiber diffraction data by long-range normal modes.
The atomic model of F-actin was refined against fiber diffraction data using long-range normal modes as adjustable parameters to account for the collective long-range filamentous deformations. To determine the effect of long-range deformations on the refinement, each of the four domains of G-actin was treated as a rigid body. It was found that among all modes, the bending modes make the most significant contributions to the improvement of the refinement. Inclusion of only 7-9 bending modes as adjustable parameters yielded a lowest R-factor of 6.3%. These results demonstrate that employing normal modes as refinement parameters has the advantage of using a small number of adjustable parameters to achieve a good fitting efficiency. Such a refinement procedure may therefore prevent the refinement from overfitting the structural model. More importantly, the results of this study demonstrate that, for any fiber diffraction data, a substantial amount of refinement error is due to long-range deformations, especially the bending, of the filaments. The effects of these intrinsic deformations cannot be easily compensated for by adjusting local structural parameters, and must be properly accounted for in the refinement to achieve improved fit of refined models with experimental diffraction data.


Mycobacterial lipoarabinomannan recognition requires a receptor that shares components of the endotoxin signaling system.
Phagocytic leukocytes respond to a variety of bacterial products including Gram-negative bacterial LPS and mycobacterial lipoarabinomannan (LAM). Anti-CD14 mAbs have been shown to block LPS and LAM activation of myeloid cells, suggesting that CD14 is required for cellular recognition of both ligands. Activation of undifferentiated promonomyelocytic THP-1 cells with LAM or LPS under serum-free conditions was enhanced in the presence of recombinant soluble CD14 (rsCD14). LPS binding protein (LBP), which is present in normal serum, further enhanced the sensitivity of undifferentiated THP-1 cells to both ligands even in the absence of rsCD14. Although CD14-transfected Chinese hamster ovary and human HT1080 fibrosarcoma cell lines can be activated by LPS, neither cell line was activated by LAM. Furthermore, U373 astrocytoma cells, which respond to LPS using sCD14 and LBP, failed to be activated by LAM in the presence of rsCD14 and rLBP. We then tested the effects of lipid IVA and Rhodobacter sphaeroides lipid A, compounds that function as endotoxin inhibitors in human cells by interacting with a molecule thought to be a CD14-dependent LPS signal transducer. Both lipid IVA and R. sphaeroides lipid A inhibited the effects of LPS and LAM in THP-1 cells. Thus, the LPS and LAM receptors share CD14, LBP, and a putative endotoxin antagonist-inhibitable signal transducing component. However, the LAM signaling system appears to require an additional receptor component whose expression is restricted to cells of hemopoietic origin.


Overexpression of basic fibroblast growth factor (FGF-2) downregulates Bcl-2 and promotes apoptosis in MCF-7 human breast cancer cells.
Basic fibroblast growth factor (bFGF, FGF-2), a classical transforming factor, mitogen, and survival factor in multiple cell types, and has a paradoxic role in mammary epithelial cell transformation and proliferation. We have also demonstrated that recombinant FGF-2 uncharacteristically promotes cell death in MCF-7 human breast cancer cells. In this study, we investigated the effects of FGF-2 overexpression on survival in the same MCF-7 cells. In eight breast cancer cell lines and two nontransformed mammary epithelial cell lines, we demonstrated that high levels of Bcl-2 are only expressed in cells with undetectable levels of FGF-2 on western blot. In retrovirally transduced MCF-7 cells expressing both cytoplasm- and nucleus-localizing FGF-2 species and ones expressing only cytoplasm-localizing FGF-2 species, Bcl-2 levels were strongly decreased at both the mRNA and protein levels. Immunoprecipitation of Bax demonstrated a decreased association of Bax with Bcl-2 in these cells. Levels of Bax did not correlate with expression of FGF-2 in the 10 cell lines or in MCF-7 cells. The clonogenic potential of MCF-7 cells in tissue culture was decreased by the expression of FGF-2 and was additively suppressed by the chemotherapeutic agents etoposide and 5-fluorouracil in a dose and time dependent manner. MCF-7 cells overexpressing FGF-2 had a greater rate of programmed cell death at baseline and in response to etoposide and 5-fluorouracil in a TUNEL assay by immunofluorescent microphotography and by flow cytometric quantitation. The pro-apoptotic effect of FGF-2 overexpression on the chemosensitivity of these cells was confirmed by quantitative morphologic determination. These data demonstrate that the expression of FGF-2 downregulates Bcl-2 and promotes programmed cell death in MCF-7 human breast cancer cells.


Adaptive image contrast enhancement using generalizations of histogram equalization.
This paper proposes a scheme for adaptive image-contrast enhancement based on a generalization of histogram equalization (HE). HE is a useful technique for improving image contrast, but its effect is too severe for many purposes. However, dramatically different results can be obtained with relatively minor modifications. A concise description of adaptive HE is set out, and this framework is used in a discussion of past suggestions for variations on HE. A key feature of this formalism is a "cumulation function," which is used to generate a grey level mapping from the local histogram. By choosing alternative forms of cumulation function one can achieve a wide variety of effects. A specific form is proposed. Through the variation of one or two parameters, the resulting process can produce a range of degrees of contrast enhancement, at one extreme leaving the image unchanged, at another yielding full adaptive equalization.


Association of Speech Recognition Thresholds With Brain Volumes and White Matter Microstructure: The Rotterdam Study.
Brain volumetric declines may underlie the association between hearing loss and dementia. While much is known about the peripheral auditory function and brain volumetric declines, poorer central auditory speech processing may also be associated with decreases in brain volumes. Central auditory speech processing, measured by the speech recognition threshold (SRT) from the Digits-in-Noise task, and neuroimaging assessments (structural magnetic resonance imaging [MRI] and fractional anisotropy and mean diffusivity from diffusion tensor imaging), were assessed cross-sectionally in 2,368 Rotterdam Study participants aged 51.8 to 97.8 years. SRTs were defined continuously and categorically by degrees of auditory performance (normal, insufficient, and poor). Brain volumes from structural MRI were assessed on a global and lobar level, as well as for specific dementia-related structures (hippocampus, entorhinal cortex, parahippocampal gyrus). Multivariable linear regression models adjusted by age, age-squared, sex, educational level, alcohol consumption, intracranial volume (MRI only), cardiovascular risk factors (hypertension, diabetes, obesity, current smoking), and pure-tone average were used to determine associations between SRT and brain structure. Poorer central auditory speech processing was associated with larger parietal lobe volume (difference in mL per dB increase= 0.24, 95% CI: 0.05, 0.42), but not with diffusion tensor imaging measures. Degrees of auditory performance were not associated with brain volumes and white matter microstructure. Central auditory speech processing in the presence of both vascular burden and pure-tone average may not be related to brain volumes and white matter microstructure. Longitudinal follow-up is needed to explore these relationships thoroughly.


Plasticity in the neural coding of auditory space in the mammalian brain.
Sound localization relies on the neural processing of monaural and binaural spatial cues that arise from the way sounds interact with the head and external ears. Neurophysiological studies of animals raised with abnormal sensory inputs show that the map of auditory space in the superior colliculus is shaped during development by both auditory and visual experience. An example of this plasticity is provided by monaural occlusion during infancy, which leads to compensatory changes in auditory spatial tuning that tend to preserve the alignment between the neural representations of visual and auditory space. Adaptive changes also take place in sound localization behavior, as demonstrated by the fact that ferrets raised and tested with one ear plugged learn to localize as accurately as control animals. In both cases, these adjustments may involve greater use of monaural spectral cues provided by the other ear. Although plasticity in the auditory space map seems to be restricted to development, adult ferrets show some recovery of sound localization behavior after long-term monaural occlusion. The capacity for behavioral adaptation is, however, task dependent, because auditory spatial acuity and binaural unmasking (a measure of the spatial contribution to the "cocktail party effect") are permanently impaired by chronically plugging one ear, both in infancy but especially in adulthood. Experience-induced plasticity allows the neural circuitry underlying sound localization to be customized to individual characteristics, such as the size and shape of the head and ears, and to compensate for natural conductive hearing losses, including those associated with middle ear disease in infancy.


Cerebellar hemorrhage: reliability of clinical evaluation.
Surgery without confirmatory radiological contrast studies has been advocated in patients suspected of having a cerebellar hemorrhage. To determine the reliabiligy of the clinical evaluation, records were reviewed of 33 patients in whom the diagnosis of cerebellar hemorrhage was initially suspected or subsequently confirmed. In 13 patients the correct diagnosis had been made initially by clinical evaluation, but in ten patients the correct diagnosis was not suspected at the initial evaluation. The remaining ten patients had typical backgrounds, symptoms, and signs of a spontaneous cerebellar hemorrhage, but radiological contrast studies and clinical observation indicated that other neurological lesions were responsible. Thus, utilizing solely the clinical evaluation, the diagnosis of cerebellar hemorrhage may be made only with difficulty and not with the certainty required for emergency surgery.


Nonalcoholic fatty liver disease and vascular disease: state-of-the-art.
Nonalcoholic fatty liver disease (NAFLD), the most common of chronic liver disease in Western Country, is closely related to insulin resistance and oxidative stress and includes a wide spectrum of liver diseases ranging from steatosis alone, usually a benign and non-progressive condition, to nonalcoholic steatohepatitis (NASH), which may progress to liver fibrosis and cirrhosis. NAFLD is considered the hepatic manifestation of the metabolic syndrome with which shares several characteristics, however recent data suggest that NAFLD is linked to increased cardiovascular risk independently of the broad spectrum of risk factors of metabolic syndrome. Accumulating evidence suggests that the clinical burden of NAFLD is not restricted to liver-related morbidity and mortality, with the majority of deaths in NAFLD patients related to cardiovascular disease and cancer and not to the progression of liver disease. Retrospective and prospective studies provide evidence of a strong association between NAFLD and subclinical manifestation of atherosclerosis (increased intima-media thickness, endothelial dysfunction, arterial stiffness, impaired left ventricular function and coronary calcification). A general agreement emerging from these studies indicates that patients with NASH are at higher risk of cardiovascular diseases than those with simple steatosis, emphasizing the role of chronic inflammation in the pathogenesis of atherosclerosis of these patients. It is very likely that the different mechanisms involved in the pathogenesis of atherosclerosis in patients with NAFLD have a different relevance in the patients according to individual genetic background. In conclusion, in the presence of NAFLD patients should undergo a complete cardiovascular evaluation to prevent future atherosclerotic complications. Specific life-style modification and aggressive pharmaceutical modification will not only reduce the progression of liver disease, but also reduce morbidity for cardiovascular disease improving overall prognosis and survival.


The brain-gut axis in irritable bowel syndrome--clinical aspects.
Irritable bowel syndrome (IBS) is the most common chronic gastrointestinal (GI) disorder, affecting about 20% of the world's population. Chronic abdominal pain or discomfort relieved by defecation and associated with altered bowel habits are the mainstay in diagnosis. The pathophysiology of IBS remains unknown. This biopsychosocial disorder involves dysregulation of the nervous system, altered intestinal motility, and increased visceral sensitivity. All of these result from dysregulation of the bidirectional communication between the gut with its enteric nervous system and the brain (the brain-gut axis), modulated by various psychosocial and environmental factors (e.g. infection, inflammation). Numerous neurotransmitters are found in the brain and gut that regulate GI activities, including 5-hydroxytryptamine (5-HT, serotonin) and its 5-HT3 and 5-HT4 receptors. The current approach to IBS patients is based on a positive diagnosis of the symptom complex, exclusion of underlying organic disease, and institution of a therapeutic trial. Traditional symptomatic treatment has included antidiarrheals, laxatives and bulking agents/fiber, low-dose tricyclic antidepressants, antispasmodics for pain, and "alternative" therapies (e.g. psychotherapy, hypnotherapy). The scientific evidence supporting this therapy is limited. Novel approaches include visceral analgesics and serotonin agonists and antagonists. In patients with severe diarrhea, 5-HT3 receptor antagonists (e.g. alosetron) and selective M3-type anticholinergics are indicated, in constipation 5-HT4 agonists (e.g. tegaserod), and in pain alfa2-adrenergics (e.g. clonidine), cholecystokinin antagonists, kappa-opioid agonists (e.g. fedotozine), and neurokinin antagonists; some of these agents are still being investigated. Understanding the brain-gut axis is crucial in the development of effective therapies for IBS.


Tuberculosis management by private practitioners in Mumbai, India: has anything changed in two decades?
Mumbai, India. A study conducted in Mumbai two decades ago revealed the extent of inappropriate tuberculosis (TB) management practices of private practitioners. Over the years, India's national TB programme has made significant progress in TB control. Efforts to engage private practitioners have also been made with several successful documented public-private mix initiatives in place. To study prescribing practices of private practitioners in the treatment of tuberculosis, two decades after a similar study conducted in the same geographical area revealed dismal results. Survey questionnaire administered to practicing general practitioners attending a continuing medical education programme. The participating practitioners had never been approached or oriented by the local TB programme. Only 6 of the 106 respondents wrote a prescription with a correct drug regimen. 106 doctors prescribed 63 different drug regimens. There was tendency to over treat with more drugs for longer durations. Only 3 of the 106 respondents could write an appropriate prescription for treatment of multidrug-resistant TB. With a vast majority of private practitioners unable to provide a correct prescription for treating TB and not approached by the national TB programme, little seems to have changed over the years. Strategies to control TB through public sector health services will have little impact if inappropriate management of TB patients in private clinics continues unabated. Large scale implementation of public-private mix approaches should be a top priority for the programme. Ignoring the private sector could worsen the epidemic of multidrug-resistant and extensively drug-resistant forms of TB.


Application of adaptive design and decision making to a phase II trial of a phosphodiesterase inhibitor for the treatment of intermittent claudication.
Claudication secondary to peripheral artery disease (PAD) is associated with substantial functional impairment. Phosphodiesterase (PDE) inhibitors have been shown to increase walking performance in these patients. K-134 is a selective PDE 3 inhibitor being developed as a potential treatment for claudication. The use of K-134, as with other PDE 3 inhibitors, in patients with PAD raises important safety and tolerability concerns, including the induction of cardiac ischemia, tachycardia, and hypotension. We describe the design, oversight, and implementation of an adaptive, phase II, dose-finding trial evaluating K-134 for the treatment of stable, intermittent claudication. The study design was a double-blind, multi-dose (25 mg, 50 mg, and 100 mg of K-134), randomized trial with both placebo and active comparator arms conducted in the United States and Russia. The primary objective of the study was to compare the highest tolerable dose of K-134 versus placebo using peak walking time after 26 weeks of therapy as the primary outcome. Study visits with intensive safety assessments were included early in the study period to provide data for adaptive decision making. The trial used an adaptive, dose-finding strategy to efficiently identify the highest dose(s) most likely to be safe and well tolerated, based on the side effect profiles observed within the trial, so that less promising doses could be abandoned. Protocol specified criteria for safety and tolerability endpoints were used and modeled prior to the adaptive decision making. The maximum target sample size was 85 subjects in each of the retained treatment arms. When 199 subjects had been randomized and 28-day data were available from 143, the Data Monitoring Committee (DMC) recommended termination of the lowest dose (25 mg) treatment arm. Safety evaluations performed during 14- and 28-day visits which included in-clinic dosing and assessments at peak drug concentrations provided core data for the DMC review. At the time of review, no subject in any of the five treatment arms (placebo, three K-134-containing arms, and cilostazol) had met pre-specified definitions for resting tachycardia or ischemic changes on exercise ECG. If, instead of dropping the 25-mg K-134 treatment arm, all arms had been continued to full enrollment, then approximately 43 additional research subjects would have been required to complete the trial. In this phase II, dose-finding trial of K-134 in the treatment of stable intermittent claudication, no concerning safety signals were seen at interim analysis, allowing the discontinuation of the lowest-dose-containing arm and the retention of the two highest-dose-containing arms. The adaptive design facilitated safe and efficient evaluation of K-134 in this high-risk cardiovascular population. ClinicalTrials.gov: NCT00783081.


Dual regeneration of muscle and nerve by intravenous administration of human amniotic fluid-derived mesenchymal stem cells regulated by stromal cell-derived factor-1α in a sciatic nerve injury model.
Human amniotic fluid-derived mesenchymal stem cells (AFMSCs) have been shown to promote peripheral nerve regeneration. The expression of stromal cell-derived factor-1α (SDF-1α) in the injured nerve exerts a trophic effect by recruiting progenitor cells that promote nerve regeneration. In this study, the authors investigated the feasibility of intravenous administration of AFMSCs according to SDF-1α expression time profiles to facilitate neural regeneration in a sciatic nerve crush injury model. Peripheral nerve injury was induced in 63 Sprague-Dawley rats by crushing the left sciatic nerve using a vessel clamp. The animals were randomized into 1 of 3 groups: Group I, crush injury as the control; Group II, crush injury and intravenous administration of AFMSCs (5 × 10(6) cells for 3 days) immediately after injury (early administration); and Group III, crush injury and intravenous administration of AFMSCs (5 × 10(6) cells for 3 days) 7 days after injury (late administration). Evaluation of neurobehavior, electrophysiological study, and assessment of regeneration markers were conducted every week after injury. The expression of SDF-1α and neurotrophic factors and the distribution of AFMSCs in various time profiles were also assessed. Stromal cell-derived factor-1α increased the migration and wound healing of AFMSCs in vitro, and the migration ability was dose dependent. Crush injury induced the expression of SDF-1α at a peak of 10-14 days either in nerve or muscle, and this increased expression paralleled the expression of its receptor, chemokine receptor type-4 (CXCR-4). Most AFMSCs were distributed to the lung during early or late administration. Significant deposition of AFMSCs in nerve and muscle only occurred in the late administration group. Significantly enhanced neurobehavior, electrophysiological function, nerve myelination, and expression of neurotrophic factors and acetylcholine receptor were demonstrated in the late administration group. Amniotic fluid-derived mesenchymal stem cells can be recruited by expression of SDF-1α in muscle and nerve after nerve crush injury. The increased deposition of AFMSCs paralleled the expression profiles of SDF-1α and its receptor CXCR-4 in either muscle or nerve. Administration of AFMSCs led to improvements in neurobehavior and expression of regeneration markers. Intravenous administration of AFMSCs may be a promising alternative treatment strategy in peripheral nerve disorder.


Understanding the Seed-Mediated Growth of Gold Nanorods through a Fractional Factorial Design of Experiments.
Since the development of simple, aqueous protocols for the synthesis of anisotropic metal nanoparticles, research into many promising, valuable applications of gold nanorods has grown considerably, but a number of challenges remain, including gold-particle yield, robustness to minor impurities, and precise control of gold nanorod surface chemistry. Herein we present the results of a composite fractional factorial series of experiments designed to screen seven additional potential avenues of control and to understand the seed-mediated silver-assisted synthesis of gold nanorods. These synthesis variables are the amount of sodium borohydride used and the rate of stirring when producing seed nanoparticles, the age of and the amount of seeds added, the reaction temperature, the amounts of silver nitrate and ascorbic acid added, and the age of the reduced growth solution before seed nanoparticles are added to initiate rod formation. This statistical experimental design and analysis method, besides determining which experimental variables are important and which are not when synthesizing gold nanorods (and quantifying their effects), gives further insight into the mechanism of growth by measuring the degree to which variables interact with each other by mapping out their mechanistic connections. This work demonstrates that when forming gold nanorods by the reduction of auric ions by ascorbic acid onto seed nanoparticles, ascorbic acid determines how much gold is reduced, and the amount of seeds determine how it is divided, yet both influence the intrinsic growth rates, in both width and length, of the forming nanorods. Furthermore, this work shows that the reduction of gold proceeds via direct reduction on the surface of seeds and not through a disproportionation reaction. Further control over the length of gold nanorods can be achieved by tuning the amount of silver nitrate or the reaction temperature. This work shows that silver does not directly influence rod length or width, and a new primary role for silver is proposed as a catalyst promoting the reduction of gold on the ends of forming nanorods. Furthermore, this silver catalyst is removed from the reaction by adsorption onto the surface of the growing nanorod. This work also demonstrates the importance of freshly prepared silver nitrate and ascorbic acid solutions, free from even a few hours of photodegradation, in preparing gold nanorods with high shape purity and gold yield.


Silencing of human DNA polymerase λ causes replication stress and is synthetically lethal with an impaired S phase checkpoint.
Human DNA polymerase (pol) λ functions in base excision repair and non-homologous end joining. We have previously shown that DNA pol λ is involved in accurate bypass of the two frequent oxidative lesions, 7,8-dihydro-8-oxoguanine and 1,2-dihydro-2-oxoadenine during the S phase. However, nothing is known so far about the relationship of DNA pol λ with the S phase DNA damage response checkpoint. Here, we show that a knockdown of DNA pol λ, but not of its close homologue DNA pol β, results in replication fork stress and activates the S phase checkpoint, slowing S phase progression in different human cancer cell lines. We furthermore show that DNA pol λ protects cells from oxidative DNA damage and also functions in rescuing stalled replication forks. Its absence becomes lethal for a cell when a functional checkpoint is missing, suggesting a DNA synthesis deficiency. Our results provide the first evidence, to our knowledge, that DNA pol λ is required for cell cycle progression and is functionally connected to the S phase DNA damage response machinery in cancer cells.


Occurrence of Impatiens necrotic spot virus and Tomato spotted wilt virus on Potatoes in Iran.
There have been an increasing number of records of the natural infection of various crops and ornamentals in Iran with Impatiens necrotic spot virus (INSV), Tomato spotted wilt virus (TSWV), and Tomato yellow fruit ring virus (TYFRV), a recently proposed species in the genus Topovirus (3). TYFRV, originally believed to be TSWV and named as such, has been previously reported to occur in Iranian potato fields (2). During the growing seasons of 2004 to 2006, surveys were conducted in potato fields in different potato-producing (Solanum tuberosum) provinces of Iran (Ardabil, Azarbayejan-e-sharqi, Chaharmahal-va-bakhtiyari, Esfahan, Hamedan, Kerman, Khorasan, Khuzestan, Lorestan, Tehran, Qazvin, and Zanjan) to detect the presence of Tospovirus spp. infecting this crop, including Groundnut ringspot virus (GRSV), INSV, Iris yellow spot virus (IYSV), Tomato chlorotic spot virus (TCSV), TSWV, TYFRV, and Watermelon silver mottle virus (WSMoV). Overall, 186 fields were surveyed, and 2,823 potato leaf samples from plants showing tospovirus-like symptoms of chlorotic or necrotic spots, chlorosis, and necrosis were collected before or through the flowering stage, approximately 50 to 90 days after planting. Each leaf sample was tested by double-antibody sandwich (DAS)-ELISA using specific antisera (Bioreba, Reinach, Switzerland; Loewe, Sauerlach, Germany; DSMZ, Braunschweig, Germany) for the presence of the aforementioned tospoviruses. TYFRV, TSWV, and INSV were found in 24.0, 4.1, and 0.4% of the samples collected from 133, 51, and 7 fields surveyed, respectively. None of the samples had a positive reaction in ELISA to GRSV, IYSV, TCSV, and WSMoV. To confirm this testing, a number of the leaf samples that were found to be positive for INSV, TSWV, and TYFRV in ELISA tests were mechanically inoculated on Petunia × hybrid and Nicotiana benthamiana; the inoculated plants showed typical necrotic local lesions of tospoviruses and chlorotic or necrotic spots followed by systemic infection, respectively; their infection was subsequently confirmed by ELISA. The samples also were tested by reverse transcription-PCR technique using previously described specific primers (1,4). The PCR reaction resulted in the specific amplification of a 0.59-, 0.71-, and 0.67-kb (or 1.2-kb) fragment of INSV, TSWV, and TYFRV RNAs, respectively. This study showed that tospoviruses, especially TYFRV, are widespread in Iranian potato fields. It is hoped that the results may help us to improve a seed potato certification program in the future. To our knowledge, this is the first report of INSV and TSWV from potatoes in Iran. References: (1) A. R. Golnaraghi et al. Plant Dis. 92:1280, 2008. (2) R. Pourrahim et al. Plant Dis. 84:442, 2001. (3) S. Winter et al. Plant Pathol. 55:287, 2006. (4) H. Uga and S. Tsuda. Phytopathology 95:166, 2005.


Simulations of (an)isotropic diffusion on curved biological surfaces.
We present a computational particle method for the simulation of isotropic and anisotropic diffusion on curved biological surfaces that have been reconstructed from image data. The method is capable of handling surfaces of high curvature and complex shape, which are often encountered in biology. The method is validated on simple benchmark problems and is shown to be second-order accurate in space and time and of high parallel efficiency. It is applied to simulations of diffusion on the membrane of endoplasmic reticula (ER) in live cells. Diffusion simulations are conducted on geometries reconstructed from real ER samples and are compared to fluorescence recovery after photobleaching experiments in the same ER samples using the transmembrane protein tsO45-VSV-G, C-terminally tagged with green fluorescent protein. Such comparisons allow derivation of geometry-corrected molecular diffusion constants for membrane components from fluorescence recovery after photobleaching data. The results of the simulations indicate that the diffusion behavior of molecules in the ER membrane differs significantly from the volumetric diffusion of soluble molecules in the lumen of the same ER. The apparent speed of recovery differs by a factor of approximately 4, even when the molecular diffusion constants of the two molecules are identical. In addition, the specific shape of the membrane affects the recovery half-time, which is found to vary by a factor of approximately 2 in different ER samples.


Effects of ginkgo biloba extract on cultured human retinal pigment epithelial cells under chemical hypoxia.
To investigate the effects of Ginkgo biloba extract (GBE) on expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) in retinal pigment epithelial (RPE) cells under chemical hypoxia. RPE cells (ARPE-19) were cultured in either untreated media (control group), media treated with 200 μM cobalt chloride (hypoxia group) or media treated with both 200 μM cobalt chloride and 100 μg/ml GBE (hypoxia + GBE group) for various amounts of time. HIF-1α and VEGF expression were compared between groups. HIF-1α and VEGF messenger RNA (mRNA) were quantified using real-time polymerase chain reaction (PCR). HIF-1α of extracted nuclei and VEGF of the media were quantified using enzyme-linked immunosorbent assay (ELISA). The expression of HIF-1α was also assessed with Western blot and immunocytochemistry. HIF-1α mRNA, VEGF mRNA, HIF-1α and VEGF levels were higher in the hypoxia group compared with the control group; however, real-time PCR revealed decreased expression of HIF-1α mRNA and VEGF mRNA in the hypoxia + GBE group compared with the hypoxia group. In the ELISA, the HIF-1α and VEGF protein concentrations also decreased with GBE treatment. Western blot and immunostaining showed that the intensity of HIF-1α signals in the hypoxia + GBE group was lower than that of the hypoxia group. GBE reduced HIF-1α and VEGF expression in RPE cells cultured under chemical hypoxia in vitro.


Role of the HCF-1 basic region in sustaining cell proliferation.
The human herpes simplex virus-associated host cell factor 1 (HCF-1) is a conserved human transcriptional co-regulator that links positive and negative histone modifying activities with sequence-specific DNA-binding transcription factors. It is synthesized as a 2035 amino acid precursor that is cleaved to generate an amino- (HCF-1(N)) terminal subunit, which promotes G1-to-S phase progression, and a carboxy- (HCF-1(C)) terminal subunit, which controls multiple aspects of cell division during M phase. The HCF-1(N) subunit contains a Kelch domain that tethers HCF-1 to sequence-specific DNA-binding transcription factors, and a poorly characterized so called "Basic" region (owing to a high ratio of basic vs. acidic amino acids) that is required for cell proliferation and has been shown to associate with the Sin3 histone deacetylase (HDAC) component. Here we studied the role of the Basic region in cell proliferation and G1-to-S phase transition assays. Surprisingly, much like the transcriptional activation domains of sequence-specific DNA-binding transcription factors, there is no unique sequence within the Basic region required for promoting cell proliferation or G1-to-S phase transition. Indeed, the ability to promote these activities is size dependent such that the shorter the Basic region segment the less activity observed. We find, however, that the Basic region requirements for promoting cell proliferation in a temperature-sensitive tsBN67 cell assay are more stringent than for G1-to-S phase progression in an HCF-1 siRNA-depletion HeLa-cell assay. Thus, either half of the Basic region alone can support G1-to-S phase progression but not cell proliferation effectively in these assays. Nevertheless, the Basic region displays considerable structural plasticity because each half is able to promote cell proliferation when duplicated in tandem. Consistent with a potential role in promoting cell-cycle progression, the Sin3a HDAC component can associate independently with either half of the Basic region fused to the HCF-1 Kelch domain. While conserved, the HCF-1 Basic region displays striking structural flexibility for controlling cell proliferation.


Molecular cloning and analysis of the human PCAN1 (GDEP) promoter.
Human PCAN1 (prostate cancer gene 1) is a prostate-specific gene that is highly expressed in prostate epithelial tissue, and frequently mutated in prostate tumors. To better understand the regulation of the PCAN1 gene, a 2.6-kb fragment of its 5' flanking region was obtained by PCR. Its promoter activity was examined via the dual-luciferase reporter assay after it had been cloned into a pGL(3)-basic vector generating pGL(3)-p2.6 kb and transfected into LNCaP cells. pGL(3)-basic and pGL(3)-control were respectively used as the negative and positive controls. Sequence analysis with the MatInspector database showed that some possible binding sites for the transcriptional factors, NKX3.1, P53, SP1, cEBP and the PPAR/RXR heterodimers may locate on a 2.6-kb region upstream of the PCAN1 gene. To examine the relevant regulation of PCAN1, pGL(3)-p2.6 kb was transfected into the prostate cancer cell line LNCaP, which was treated with R1881 (10(-7) approximately 10(-9) mol/l), 17beta-estradiol (17beta-E(2), 10(-7) approximately 10(-9) mol/l), all-trans-retinoic acid (all-trans-RA, 10(-5) approximately 10(-7) mol/l) or 9-cis-retinoic acid (9-cis-RA, 10(-5) approximately 10(-7) mol/l), and eukaryotic expression plasmids of NKX3.1, p53, Sp1, Pten, PPARgamma or cEBPalpha were cotransfected with pGL(3)-p2.6 kb into LNCaP cells. pRL-TK, a Renilla luciferase reporter vector, was cotransfected into all the transfection lines as an internal control. The activities of pGL(3)-p2.6 kb (PCAN1 promoter) were analyzed via the dual-luciferase reporter assay 48 h after transfection. The results showed that 9-cis-RA enhanced the PCAN1 promoter activity in a dose-dependent manner, while R1881, 17beta-E(2) and all-trans-RA had no significant effect on PCAN1 promoter activities. Cotransfection with pGL(3)-p2.6kb and the expression plasmids of NKX3.1, p53, Sp1 or Pten respectively resulted in 1.66-, 2.48-, 2.00-and 1.72-fold 2.6 kb PCAN1 promoter activity increases relative to the controls, which were cotransfected with pcDNA3.1(+), while cotransfection of PPARgamma and cEBPalpha yielded no significant effect on PCAN1 promoter activities. These results could be applied for further study of the function and transcription regulation of the PCAN1 gene in prostate development and carcinogenesis.


Intracardiac ultrasound-guided percutaneous mitral valvuloplasty.
Intracardiac echocardiography (ICE) is a relatively new method of ultrasound images useful during cardiac percutaneous interventional procedures. The first human experience with this method was published in 2000 and, since then, several original trials have enrolled this useful method, proving similar and more useful than transesophageal echocardiography in percutaneous treatment of several congenital cardiopathies, like interatrial communication, permeable oval foramen, mitral stenosis, and atrial fibrillation ablation. In this presentation, we publish a single case report of percutaneous mitral valvuloplasty under ICE guidance.


Factors associated with exclusive breastfeeding among infants under six months of age in peninsular malaysia.
Breastfeeding is accepted as the natural form of infant feeding. For mothers to be able to breastfeed exclusively to the recommended six months, it is important to understand the factors that influence exclusive breastfeeding. The aim of the study was to identify factors associated with exclusive breastfeeding in Peninsular Malaysia. This was a cross-sectional study involving 682 mother-infant pairs with infants up to six months attending maternal and child health section of the government health clinics in Klang, Malaysia. Data were collected by face-to-face interviews using a pre-tested structured questionnaire over 4 months in 2006. Data on breastfeeding were based on practice in the previous one month period. Logistic regression was used to assess the independent association between the independent variables and exclusive breastfeeding adjusting for infant age. The prevalence of exclusive breastfeeding among mothers with infants aged between one and six months was 43.1% (95% CI: 39.4, 46.8). In the multivariate model exclusive breastfeeding was positively associated with rural residence, Malay mothers, non-working and non-smoking mothers, multiparous mothers, term infants, mothers with husbands who support breastfeeding and mothers who practice bed-sharing. Interventions that seek to increase exclusive breastfeeding should focus on women who are at risk of early discontinuation of breastfeeding.


After-School Program for urban youth: Evaluation of a health careers course in New York City high schools.
Mentoring in Medicine (MIM) addresses an urgent national need for minority health professionals and promotes careers in health care for urban youth. The MIM After School Program (ASP or The Course) has as its primary objectives to provide academic enrichment in human biology and motivate disadvantaged youth to pursue a career in the health professions. Secondary objectives of The Course, although not evaluated here, are to improve students' health literacy and knowledge of healthy living behaviors. Since 2009, over 1500 middle and high school students have completed the New York City based Course, which is offered once a week over a 10 week semester in an out-of-school venue. This study assesses the success of The Course in achieving its primary objectives with 84 students at five New York City high schools during the fall 2014 semester. The Course curriculum was created especially for MIM, comprises the body's 11 organ systems, and is presented in discrete modules (one each semester), along with complementary educational activities, including field trips and class projects. This study reports on a formal evaluation using quantitative and qualitative methods. The quantitative evaluation found that the students significantly increased their knowledge of the Gastrointestinal System. Students across the academic spectrum appeared to have learned the MIM ASP Course content - high school GPA was not a predictor of knowledge acquisition. The students also reported that The Course significantly increased their self-confidence in their ability to succeed (self-efficacy). The students expressed a significant increase in five health care related attitudes and an additional increase in their ability to overcome personal issues to succeed in their career and significantly improving their feeling toward, and likely pursuit of, a health career. The students stated that The Course significantly increased their interest and intent to seek out more information about health care, participate in health care activities, and take more health care courses in high school. The qualitative evaluation found that the students and their parents were pleased with the MIM ASP Course's composition, presentation, and effectiveness. With a large majority of the parents stating that their child got out of The Course what they had hoped for and that The Course made it more likely that they would recommend a health career for their child. The students and instructional staff also identified The Course elements that they felt were most and least effective. Best practices that were used in designing and conducting The Course were identified. The MIM ASP Course appears to have achieved its principal educational objectives of providing academic enrichment in human biology and improving attitudes towards a health career for a self-selected population of disadvantaged, underrepresented minority high school students in an urban setting.


Access to water in the countries of the former Soviet Union.
During the Soviet period, authorities in the USSR invested heavily in collective farming and modernization of living conditions in rural areas. However, many problems remained, including poor access to many basic amenities such as water. Since then, the situation is likely to have changed; economic decline has coincided with migration and widening social inequalities, potentially increasing disparities within and between countries. To examine access to water and sanitation and its determinants in urban and rural areas of eight former Soviet countries. A series of nationally representative surveys in Armenia, Belarus, Georgia, Moldova, Kazakhstan, Kyrgyzstan, Russia and Ukraine was undertaken in 2001, covering 18,428 individuals (aged 18+ years). The percentage of respondents living in rural areas varied between 27 and 59% among countries. There are wide urban-rural differences in access to amenities. Even in urban areas, only about 90% of respondents had access to cold running water in their home (60% in Kyrgyzstan). In rural areas, less than one-third had cold running water in their homes (44% in Russia, under 10% in Kyrgyzstan and Moldova). Between one-third and one-half of rural respondents in some countries (such as Belarus, Kazakhstan and Moldova) obtained their water from wells and similar sources. Access to hot running water inside the homes was an exception in rural households, reflecting the lack of modern heating methods in villages. Similarly, indoor access to toilets is common in urban areas but rare in rural areas. Access to all amenities was better in Russia compared with elsewhere in the region. Indoor access to cold water was significantly more common among rural residents living in apartments, and in settlements served by asphalt roads rather than dirt roads. People with more assets or income and living with other people were significantly more likely to have water on tap. In addition, people who had moved in more recently were more likely to have an indoor water supply. This was the largest single study of its kind undertaken in this region, and demonstrates that a significant number of people living in rural parts of the former Soviet Union do not have indoor access to running water and sanitation. There are significant variations among countries, with the worse situation in central Asia and the Caucasus, and the best situation in Russia. Access to water strongly correlates with socio-economic characteristics. These findings suggest a need for sustained investment in rebuilding basic infrastructure in the region, and monitoring the impact of living conditions on health.


Super-capacity me! Super-capacity and violations of race independence for self- but not for reward-associated stimuli.
Participants are biased in responding to stimuli associated with themselves compared with stimuli related to other people. This self-bias may reflect the reward value of self-related stimuli (Sui, He, & Humphreys, 2012). In this article, we examined the identification of self- and reward-associated stimuli under conditions in which either single or redundant stimuli were presented. The redundant stimuli could be the same shape or they could be different shapes both associated with either the self or a friend or high or low reward. We formally tested whether the redundant stimuli violated the independent race model for the identification of multiple stimuli (Miller, 1982) and whether the redundant stimuli were processed with super- or limited-capacity (Townsend & Eidels, 2011). We found that redundant self stimuli alone both violated the independent race model and were processed with super-capacity. In contrast, the redundant high reward stimuli did not show race inequality and were associated with limited capacity processing. The data advance our theoretical understanding of self bias both by demonstrating that it can be distinguished from effects of reward, and by suggesting that self-bias can result from the enhanced integration of stimuli associated with the self. The implications for understanding self bias effects are discussed.


Mass transport at infinite regular arrays of microband electrodes submitted to natural convection: theory and experiments.
Mass transport at infinite regular arrays of microband electrodes was investigated theoretically and experimentally in unstirred solutions. Even in the absence of forced hydrodynamics, natural convection limits the convection-free domain up to which diffusion layers may expand. Hence, several regimes of mass transport may take place according to the electrode size, gap between electrodes, time scale of the experiment, and amplitude of natural convection. They were identified through simulation by establishing zone diagrams that allowed all relative contributions to mass transport to be delineated. Dynamic and steady-state regimes were compared to those achieved at single microband electrodes. These results were validated experimentally by monitoring the chronoamperometric responses of arrays with different ratios of electrode width to gap distance and by mapping steady-state concentration profiles above their surface through scanning electrochemical microscopy.


Total internal reflection-based planar waveguide solar concentrator with symmetric air prisms as couplers.
We present a waveguide coupling approach for planar waveguide solar concentrator. In this approach, total internal reflection (TIR)-based symmetric air prisms are used as couplers to increase the coupler reflectivity and to maximize the optical efficiency. The proposed concentrator consists of a line focusing cylindrical lens array over a planar waveguide. The TIR-based couplers are located at the focal line of each lens to couple the focused sunlight into the waveguide. The optical system was modeled and simulated with a commercial ray tracing software (Zemax). Results show that the system used with optimized TIR-based couplers can achieve 70% optical efficiency at 50 × geometrical concentration ratio, resulting in a flux concentration ratio of 35 without additional secondary concentrator. An acceptance angle of ± 7.5° is achieved in the x-z plane due to the use of cylindrical lens array as the primary concentrator.


Benefits and costs of ecological restoration: Rapid assessment of changing ecosystem service values at a U.K. wetland.
Restoration of degraded land is recognized by the international community as an important way of enhancing both biodiversity and ecosystem services, but more information is needed about its costs and benefits. In Cambridgeshire, U.K., a long-term initiative to convert drained, intensively farmed arable land to a wetland habitat mosaic is driven by a desire both to prevent biodiversity loss from the nationally important Wicken Fen National Nature Reserve (Wicken Fen NNR) and to increase the provision of ecosystem services. We evaluated the changes in ecosystem service delivery resulting from this land conversion, using a new Toolkit for Ecosystem Service Site-based Assessment (TESSA) to estimate biophysical and monetary values of ecosystem services provided by the restored wetland mosaic compared with the former arable land. Overall results suggest that restoration is associated with a net gain to society as a whole of $199 ha(-1)y(-1), for a one-off investment in restoration of $2320 ha(-1). Restoration has led to an estimated loss of arable production of $2040 ha(-1)y(-1), but estimated gains of $671 ha(-1)y(-1) in nature-based recreation, $120 ha(-1)y(-1) from grazing, $48 ha(-1)y(-1) from flood protection, and a reduction in greenhouse gas (GHG) emissions worth an estimated $72 ha(-1)y(-1). Management costs have also declined by an estimated $1325 ha(-1)y(-1). Despite uncertainties associated with all measured values and the conservative assumptions used, we conclude that there was a substantial gain to society as a whole from this land-use conversion. The beneficiaries also changed from local arable farmers under arable production to graziers, countryside users from towns and villages, and the global community, under restoration. We emphasize that the values reported here are not necessarily transferable to other sites.


Short-term exposure of multicellular tumor spheroids of a human glioma cell line to the glycolytic inhibitor 2-deoxy-D-glucose is more toxic than continuous exposure.
The glycolytic inhibitor 2-deoxy-D-glucose (2-DG) has been used as a therapeutic agent and as an adjuvant in cancer therapy with either weekly fractions of the treatment or daily administration. While the weekly fraction has often been found to be nontoxic and effective, other treatment regimes are tolerated to a relatively lesser extent. It was therefore, considered worthwhile to investigate the efficacy of short- and long-term exposure of tumor cells to 2-DG under the controlled conditions. Seven-day-old MTS were exposed to 2-DG (5 mM, equimolar to glucose concentration in media) for different time intervals (30 min to 24 h) trypsinized and plated for clonogenicity. Alternatively, spheroids were grown either continuously in the presence of 2-DG or were treated with 2-DG for 2 h (short-term exposure) and grown in 2-DG-free media for 21 days and assessed for spheroid growth, cell viability, apoptosis, cytogenetic damage, mitochondrial status, and oxidative stress. Exposure of spheroids to 2-DG for 2-4 h induced 30% cell death (SF 0.70) while, a 24-h exposure resulted in only a marginal decrease in clonogenicity (SF 0.95). Furthermore, the spheroids disintegrated completely by 28 days in the case of 2-h exposure to 2-DG, while spheroids grown continuously in the presence of 2-DG repopulated. The cytotoxicity following short-term exposure of MTS to 2-DG was primarily due to the induction of apoptosis revealed by morphological features as well as flow cytometric analysis of the DNA content. Interestingly however, cytogenetic damage (micronuclei induction) was observed in spheroids that were continuously exposed to 2-DG. Short-term exposure to 2-DG resulted in a significant increase in ROS levels and a reduction in the levels of unoxidized cardiolipin as measured by NAO suggesting the involvement of mitochondria leakiness leading to oxidative stress which, could be responsible for apoptotic cell death observed under these conditions. However, continuous exposure to 2-DG resulted in a moderate level of oxidative stress leading to the genomic instability. Preliminary studies also show that spheroids exposed continuously to 2-DG result in the development of resistance to certain chemotherapeutic drugs which could be correlated with elevated levels of mdr1. The present results suggest that a persistent down-regulation of glycolysis (as seen here with continuous exposure to 2-DG) could activate prosurvival responses besides inducing moderate levels of oxidative stress resulting in the development of resistance against therapeutic agents.


Studies on hypocholesterolemic activity of rice bran oil.
The serum total, free esterified and (LDL + VLDL)-cholesterol levels of rats maintained on a 10% refined rice bran oil diet were significantly lower than those on a 10% groundnut oil diet; HDL-cholesterol showed a tendency to be higher. Addition of oryzanol at 0.5% level to the diet containing rice bran oil showed a further significant decrease in serum total cholesterol. Liver lipids of rats fed bran oil were also markedly lower than their groundnut oil fed counterparts. Though the liver lipids of rats fed oryzanol along with RBO showed a further lowering, it was not statistically significant. The cholesterol lowering ability of rice bran oil appears to be due to oryzanol and to some other components of the unsaponifiable matter.


Thymus vulgaris L. extract has antimicrobial and anti-inflammatory effects in the absence of cytotoxicity and genotoxicity.
This study evaluated the biological effects of the T. vulgaris L. extract., such as antimicrobial activity on planktonic cultures and mono- and polymicrobial biofilms, cytotoxicity, anti-inflammatory activity and genotoxicity. Monomicrobial biofilms of Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and Pseudomonas aeruginosa and polymicrobial biofilms composed by C. albicans with each bacterium were formed for 48h and exposed for 5min to the plant extract. Murine macrophages (RAW 264.7), human gingival fibroblasts (FMM-1), human breast carcinoma cells (MCF-7) and cervical carcinoma cells (HeLa) were also exposed to the plant extract for 5min and the cell viability were analyzed by MTT, neutral red (NR) and crystal violet (CV) assays. Interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) produced by RAW 264.7 was quantified by ELISA, after 24h exposure to the plant extract, both in the absence and presence of lipopolysaccharide (LPS) from Escherichia coli. Genotoxicity of the plant extract was evaluated by micronucleus formation (MN) in 1000 cells. The results were analyzed by T-Test or ANOVA and Tukey's Test (P≤0.05). All biofilms showed significant reductions in CFU/mL (colony-forming units per milliliter). Cell viability was above 50% for all cell lines. Anti-inflammatory effect on the synthesis of IL-1β and TNF-α was observed. The MN was similar or lower than the control group in all cells. T. vulgaris L. extract was effective against all biofilms, promoted high cell viability, anti-inflammatory effect and presented no genotoxicity.


Patterns of dietary intake and serum carotenoid and tocopherol status are associated with biomarkers of chronic low-grade systemic inflammation and cardiovascular risk.
Dietary modification may affect inflammatory processes and protect against chronic disease. In the present study, we examined the relationship between dietary patterns, circulating carotenoid and tocopherol concentrations, and biomarkers of chronic low-grade systemic inflammation in a 10-year longitudinal study of Scottish postmenopausal women. Diet was assessed by FFQ during 1997-2000 (n 3237, mean age 54·8 (SD 2·2) years). Participants (n 2130, mean age 66·0 (SD 2·2) years) returned during 2007-11 for follow-up. Diet was assessed by FFQ (n 1682) and blood was collected for the analysis of serum high-sensitivity C-reactive protein (hs-CRP), IL-6, serum amyloid A, E-selectin, lipid profile and dietary biomarkers (carotenoids, tocopherols and retinol). Dietary pattern and dietary biomarker (serum carotenoid) components were generated by principal components analysis. A past 'prudent' dietary pattern predicted serum concentrations of hs-CRP and IL-6 (which decreased across the quintiles of the dietary pattern; P= 0·002 and P= 0·001, respectively; ANCOVA). Contemporary dietary patterns were also associated with inflammatory biomarkers. The concentrations of hs-CRP and IL-6 decreased across the quintiles of the 'prudent' dietary pattern (P= 0·030 and P= 0·006, respectively). hs-CRP concentration increased across the quintiles of a 'meat-dominated' dietary pattern (P= 0·001). Inflammatory biomarker concentrations decreased markedly across the quintiles of carotenoid component score (P< 0·001 for hs-CRP and IL-6, and P= 0·016 for E-selectin; ANCOVA). Prudent dietary pattern and carotenoid component scores were negatively associated with serum hs-CRP concentration (unstandardised β for prudent component: -0·053, 95% CI -0·102, -0·003; carotenoid component: -0·183, 95% CI -0·233, -0·134) independent of study covariates. A prudent dietary pattern (which reflects a diet high in the intakes of fish, yogurt, pulses, rice, pasta and wine, in addition to fruit and vegetable consumption) and a serum carotenoid profile characteristic of a fruit and vegetable-rich diet are associated with lower concentrations of intermediary markers that are indicative of CVD risk reduction.


NK, NKT and Invariant-NKT Cells in Tumor Draining Lymph Nodes of Patients with Breast Cancer.
NK (natural killer) and NKT (natural killer T) cells, as components of innate immune system, play a crucial role in tumor progression and dissemination. To investigate the percentages of NK cells, NKT cells, iNKT (invariant natural killer T) cells, total T lymphocytes as well as activated T lymphocytes, in tumor draining lymph nodes (TDLNs) of patients with breast cancer (BC) and their association with different clinic-pathological features of the patients. Axillary lymph nodes were obtained from 30 Iranian women with breast cancer. After routine pathological evaluations, mononuclear cells were separated from their lymph nodes and incubated with appropriate fluorochrome conjugated monoclonal antibodies specific for CD3, HLA-DR, CD16/56, and Vα24Jα18-TCR. Data were collected on a four-color flow cytometer and analyzed by CellQuest software. The mean percentages of NK (CD3-CD16/56+), NKT (CD3+CD16/56+) and iNKT (Vα24Jα18-TCR+) cells in TDLNs mononuclear cells of BC patients were 2.04%, 2.44% and 0.1%, respectively. A significant decrease in the percentages of NK and iNKT subsets in patients with grade I was observed compared to grade III (p=0.03 and p=0.01, respectively). Moreover, NK cells were increased in patients with grade III of BC compared to grade II (p= 0.003). The increase in the percentage of NK and iNKT cells in TDLNs of patients with higher grade of BC might suggest a suppressive phenotype for these cells in breast cancer, which merit more functional investigation.


Two-dimensional transition metal dichalcogenide/conducting polymer composites: synthesis and applications.
The exploration of hybridizing transition metal dichalcogenide (TMD) nanosheets with other materials as a unique approach for engineering their properties has attracted considerable attention from the scientific community for both basic studies and numerous potential applications. Among the various kinds of functional materials in hand, the utilization of intrinsically conducting polymers (CPs) in the construction of advanced hybrid composites with TMD nanosheets is considered as a fascinating approach. In this review, we aim at providing a survey of the literature on recent progress in composites based on 2D TMD and CPs. In this regard, we first discuss the different synthetic strategies used for the fabrication of two-dimensional transition metal dichalcogenide/conducting polymer (2D TMD/CP) composites in detail. Subsequently, we demonstrate the state-of-the-art advances in the utilization of these novel composites in promising applications such as energy storage, sensing devices, hydrogen production and so on. Finally, we also highlight some perspectives on the major challenges and future directions in this field of research.


Cancer in elderly: A study of hospital-based cancer registry in the Western Turkey.
The aim of the study is to evaluate the data of cases who were 65 years and older among cancer records from the data of Izmir Cancer Registry (ICR), in Izmir Ataturk Research Training Hospital (IAEAH), according to topography, histology, sex and having multiple tumors and to compare them with the data of cases younger than 65 years. Twenty thousands eight hundred and thirty (20,830) cases (7148 cases are ≥65 years) recorded during the period of 1993-2005 by office of ICR, located in IAEAH, were analyzed. Assessment of data was carried out by SPSS 10.0 for Windows package program. For statistical analysis Pearson's Chi-Square Test and Yates 'corrections were performed. Of 20,830 cases with cancer, recorded in the hospital data-base during 1993-2005, 34.3% were diagnosed at the age of 65 years and older. The most frequent tumor localizations in the cases younger than 65 years were breast, larynx, digestive system, skin and hematopoietic-reticuloendothelial system whereas the tumors in the, skin, digestive system and the urogenital system were more common in cases older than 65 years. When histological diagnoses were taken into consideration, basal cell carcinomas and squamous and transitional cell carcinoma were seen more frequent in the group of cases 65 years or older. The incidence of synchronous and metachronous tumors were not different in the cases younger or older than 65 years. There is a strong need to establish a communication between national and international database systems, which would yield an opportunity in the comparison of the incidence of the diseases.


The impact of out-of-pocket payments for dental care on household finances in low and middle income countries.
Dental care is extremely costly and beyond most people means in developing countries. The primary aim of this study was to determine the impact of out-of-pocket payments for dental care on household finances in 40 low and middle income countries. A second aim was to compare the burden of payments for dental care with that for other health services. We used data from 174,257 adults, aged 18 years and above, who reported their total and itemized household expenditure in the past four weeks as part of the World Health Surveys. The financial burden on households was measured using the catastrophic health expenditure (CHE) and impoverishment approaches. A household was classified as facing CHE if it spent 40% or more of its capacity to pay, and as facing impoverishment if it fell below the country-specific poverty line after spending on health care was subtracted from household expenditure. The odds of experiencing CHE and impoverishment due to expenditure on dental care were estimated from two-level logistic regression models, controlling for various individual- and country-level covariates. Households that paid for dental care had 1.88 (95% Confidence Interval: 1.78-1.99) greater odds of incurring CHE and 1.65 (95% CI: 1.52-1.80) greater odds of facing impoverishment, after adjustment for covariates. Furthermore, the impact of paying for dental care was lower than that for medications or drugs, inpatient care, outpatient care and laboratory tests but similar to that of health care products, traditional medicine and other health services. Households with recent dental care spending were more likely to use a large portion of their disposable income and fall below the poverty line. Policy makers ought to consider including dental care as part of universal health care and advocate for the inclusion of dental care coverage in health insurance packages.


Avoidance coping, binge eating, and depression: an examination of the escape theory of binge eating.
The relationship between binge eating, avoidance coping, and depression was investigated with reference to the escape theory of binge eating which predicts binge eaters will exhibit elevated avoidance coping. Undergraduate females were selected into one of three groups: control (nonrestrained/nonbinge eating) (n = 73), restrained (restrained/ nonbinge eating) (n = 61), and binge eating (restrained/binge eating) (n = 15). The groups did not differ on use of avoidance coping. Binge eating scores were significantly correlated with avoidance coping and depression, but hierarchical regression analyses indicated avoidance coping did not significantly add to the prediction of binge eating above the contribution of depression. It is proposed therefore, that it is not appropriate to use findings of elevated avoidance coping in individuals with eating disorder in support of the escape theory.


A novel noninstrumented surgical approach for foramen reconstruction for isthmic spondylolisthesis in patients with radiculopathy: preliminary clinical and radiographic outcomes.
OBJECTIVE The health care costs for instrumented spine surgery have increased dramatically in the last few decades. The authors present a novel noninstrumented surgical approach for patients with isthmic spondylolisthesis, with clinical and radiographic results. METHODS Charts of patients who underwent this technique were reviewed. The procedure consisted of nerve root decompression by reconstruction of the intervertebral foramen. This was achieved by removal of the pedicle followed by noninstrumented posterolateral fusion in which autologous bone graft from the right iliac crest was used. Outcomes regarding radicular complaints, bony fusion, progression of the slip, and complications were evaluated using patient history and radiographs obtained at follow-up intervals of 3-18 months after surgery. RESULTS A total of 58 patients with a mean age of 47 years were treated with this method. Partial removal of the pedicle was performed in 93.1% of the cases, whereas in 6.9% of the cases the entire pedicle was removed. The mean duration of surgery was 216.5 ± 54.5 minutes (range 91-340 minutes). The mean (± SD) duration of hospitalization was 10.1 ± 2.9 days (range 5-18 days). After 3 months of follow-up, 86% of the patients reported no leg pain, and this dropped to 81% at last follow-up. Radiographic follow-up showed bony fusion in 87.7% of the patients. At 1 year, 5 patients showed progression of the slip, which in 1 patient prompted a second operation within 1 year. No major complications occurred. CONCLUSIONS Treatment of isthmic spondylolisthesis by reconstruction of the intervertebral neuroforamen and posterolateral fusion in situ is a safe procedure and has comparable results with the existing techniques. Cost-effectiveness research comparing this technique to conventional instrumented fusion techniques is necessary to evaluate the merits for both patients and society.


Mutation of a putative amphipathic alpha-helix in the third intracellular domain of the platelet-activating factor receptor disrupts receptor/G protein coupling and signaling.
Platelet-activating factor (PAF) is a potent phospholipid mediator that interacts with G protein-coupled PAF receptors to elicit diverse physiological and pathophysiological actions. We recently demonstrated that the third intracellular domain of the rat PAF receptor (rPAFR) is a critical determinant in its coupling to phosphoinositide phospholipase C-activating G proteins. Here, we report identification of a putative amphipathic helix in the third intracellular domain of the rPAFR and the effects of mutational disruption of its amphipathic character on G protein coupling of and signaling by the rPAFR. Modeling of the third intracellular domain and adjacent transmembrane regions of the rPAFR identified a single amphipathic helix located in the amino-terminal region of the third intracellular domain of the receptor. Baby hamster kidney cells were transiently transfected with cDNAs encoding the rPAFR or rPAFR mutants in which nonconserved substitutions were made separately in the hydrophobic or polar face of this amphipathic helix. The number and affinity of binding sites for specific PAF receptor antagonist WEB2086 were identical in membranes prepared from rPAFR and amphipathic helix mutant PAFR transfectants. However, only membranes derived from rPAFR transfectants possessed high affinity PAF binding sites that were sensitive to the G protein-uncoupling effects of guanosine-5'-O-(3-thio)triphosphate. These results show that substitutions into either face of the amphipathic helical domain abolished the ability of the rPAFR to undergo coupling to G proteins to form a high affinity agonist/receptor/G protein ternary complex. To examine the effects of these mutations on rPAFR signaling, PAF-stimulated inositol phosphate accumulation was determined in cells transfected with cDNAs encoding the wild-type or amphipathic helix mutant PAFRs. Although PAF stimulated 10-fold increases in inositol phosphate accumulation in rPAFR transfectants, it had no effects on inositol phosphate accumulation in amphipathic helix mutant PAFR transfectants. These results suggest that an amphipathic helix located in the amino-terminal region of the third intracellular domain of the rPAFR is required for its coupling to and activation of G proteins. This study provides the first insight into the structure of the receptor interface for G protein coupling of a PAFR and suggests a conserved role of amphipathic helices in G protein coupling of receptors ranging from those for biogenic amines to the phospholipid mediator PAF.