Adhesive sealing of dentin surfaces in vitro: A review.
This review describes the evolution of the use of dental adhesives to form a tight seal of freshly prepared dentin to protect the pulp from bacterial products, during the time between crown preparation and final cementation of full crowns. The evolution of these "immediate dentin sealants" follows the evolution of dental adhesives, in general. That is, they began with multiple-step, etch-and-rinse adhesives, and then switched to the use of simplified adhesives. Literature was reviewed for evidence that bacteria or bacterial products diffusing across dentin can irritate pulpal tissues before and after smear layer removal. Smear layers can be solubilized by plaque organisms within 7-10 days if they are directly exposed to oral fluids. It is likely that smear layers covered by temporary restorations may last more than 1 month. As long as smear layers remain in place, they can partially seal dentin. Thus, many in vitro studies evaluating the sealing ability of adhesive resins use smear layer-covered dentin as a reference condition. Surprisingly, many adhesives do not seal dentin as well as do smear layers. Both in vitro and in vivo studies show that resin- covered dentin allows dentin fluid to cross polymerized resins. The use of simplified single bottle adhesives to seal dentin was a step backwards. Currently, most authorities use either 3-step adhesives such as Scotchbond Multi-Purpose or OptiBond FL or two-step self-etching primer adhesives, such as Clearfil SE, Unifil Bond or AdheSE.


Molecular basis of non-mutational derepression of ramA in Klebsiella pneumoniae.
The ram locus, consisting of the romA-ramA genes, is repressed by the tetracycline-type regulator RamR, where regulation is abolished due to loss-of-function mutations within the protein or ligand interactions. The aim of this study was to determine whether the phenothiazines (chlorpromazine and thioridazine) directly interact with RamR to derepress ramA expression. Quantitative real-time PCR analyses were performed to determine expression levels of the romA-ramA genes after exposure to the phenothiazines. Electrophoretic mobility shift assays (EMSAs) and in vitro transcription experiments were performed to show direct binding to and repression by RamR. Direct binding of the RamR protein to the phenothiazines was measured by fluorescence spectroscopy experiments and molecular docking models were generated using the RamR crystal structure. Exposure to either chlorpromazine or thioridazine resulted in the up-regulation of the romA-ramA genes. EMSAs and in vitro transcription experiments demonstrated that both agents reduce/abolish binding and enhance transcription of the target PI promoter upstream of the ramR-romA genes in Klebsiella pneumoniae compared with RamR alone. Fluorescence spectroscopy measurements demonstrated that RamR directly binds both chlorpromazine and thioridazine with micromolar affinity. Molecular docking analyses using the RamR crystal structure demonstrated that the phenothiazines interact with RamR protein through contacts described for other ligands, in addition to forming unique strong polar interactions at positions D152 and K63. These data demonstrate that phenothiazines can modulate loci linked to the microbe-drug response where RamR is an intracellular target for the phenothiazines, thus resulting in a transient non-mutational derepression of ramA concentrations.


Enhancing dye-sensitized solar cell efficiency through broadband near-infrared upconverting nanoparticles.
The inability to utilize near infrared (NIR) light has posed a stringent limitation for the efficiencies of most single-junction photovoltaic cells such as dye-sensitized solar cells (DSSCs). Here, we describe a strategy to alleviate the NIR light harvesting problem by upconverting non-responsive NIR light in a broad spectral range (over 190 nm, 670-860 nm) to narrow solar-cell-responsive visible emissions through incorporated dye-sensitized upconversion nanoparticles (DSUCNPs). Unlike typically reported UCNPs with narrow and low NIR absorption, the organic dyes (IR783) anchored on the DSUCNP surface were able to harvest NIR photons broadly and efficiently, and then transfer the harvested energy to the inorganic UCNPs (typically reported), entailing an efficient visible upconversion. We show that the incorporation of DSUCNPs into the TiO2 photoanode of a DSSC is able to elevate its efficiency from 7.573% to 8.568%, enhancing the power conversion efficiency by about 13.1%. We quantified that among the relative efficiency increase, 7.1% arose from the contribution of broad-band upconversion in DSUCNPs (about ∼3.4 times higher than the highest previously reported value of ∼2.1%), and 6.0% mainly from the scattering effect of DSUCNPs. Our strategy has immediate implications for the use of DSUCNPs to improve the performance of other types of photovoltaic devices.


Adsorption experiment of toxic micro-pollutants derived from automobiles using red soil.
In some countries, non-point source pollution derived from a city's economic activities tends to be a barrier to the improvement of water quality. Roadway runoff is known to contain toxic micro-pollutants such as polycyclic aromatic hydrocarbons (PAHs). Conversely, red soil is known to adsorb some organic matter. In this study, artificial roadway runoff water containing toxic micro-pollutants was made using roadway dust collected from a highway, and used for both batch-type tests and soil column tests with red soil in order to understand adsorption ability of the red soil on such toxic micro-pollutants, especially PAHs. In the batch-type tests, PAHs could be removed by approximately 40% when the contact time was 90 minutes. In the soil column tests, PAHs were removed by more than 80% while suspended solids were removed by more than 90%. Notably, PAHs with a high molecular weight were removed more readily in the tests than PAHs with a low molecular weight.


p53 is regulated by the lysine demethylase LSD1.
p53, the tumour suppressor and transcriptional activator, is regulated by numerous post-translational modifications, including lysine methylation. Histone lysine methylation has recently been shown to be reversible; however, it is not known whether non-histone proteins are substrates for demethylation. Here we show that, in human cells, the histone lysine-specific demethylase LSD1 (refs 3, 4) interacts with p53 to repress p53-mediated transcriptional activation and to inhibit the role of p53 in promoting apoptosis. We find that, in vitro, LSD1 removes both monomethylation (K370me1) and dimethylation (K370me2) at K370, a previously identified Smyd2-dependent monomethylation site. However, in vivo, LSD1 shows a strong preference to reverse K370me2, which is performed by a distinct, but unknown, methyltransferase. Our results indicate that K370me2 has a different role in regulating p53 from that of K370me1: K370me1 represses p53 function, whereas K370me2 promotes association with the coactivator 53BP1 (p53-binding protein 1) through tandem Tudor domains in 53BP1. Further, LSD1 represses p53 function through the inhibition of interaction of p53 with 53BP1. These observations show that p53 is dynamically regulated by lysine methylation and demethylation and that the methylation status at a single lysine residue confers distinct regulatory output. Lysine methylation therefore provides similar regulatory complexity for non-histone proteins and for histones.


The association between antihypertensive drugs and glioma.
We pursued an association between hypertension and gliomas by investigating whether antihypertensive drugs (AHD) are associated with an increased glioma risk by a population-based nested case-control study using the PHARMO database; this links dispensing records of prescription drugs to hospital discharge data on an individual basis. Pathological data were derived from the Dutch nationwide registry of histo- and cytopathology. A total of 306 glioma cases incident between 1997 and 2003 were matched to 1108 controls for year of birth, sex, geographical region and duration of follow-up. Exposure was defined as cumulative duration of AHD use and, in an alternative analysis, as cumulative dose. We estimated the magnitude of the association with conditional logistic regression analysis. Cumulative use of any AHD for more than 6 months was associated with an increased risk of glioma (OR 1.45; 95% CI 1.03-2.04). After stratification for different groups of AHD, no significantly increased risk of glioma was found for any class of AHD. After excluding a latency period of 3 years before the date of diagnosis, no association was found. In conclusion, the use of AHD seems to be associated with an increased risk of glioma, but this is probably not causal.


Perioperative steroids for lumbar disc surgery: A meta-analysis of randomized controlled trials.
Our review question was "Does perioperative steroids administration, in comparison with other treatments or placebo, improve either postoperative pain control, length of hospital stay, or return to work in patients undergoing lumbar disc surgery?" We searched PubMed, CINAHL PLUS, and Cochrane databases for randomized control trials (RCTs) studying the role of steroids for lumbar disc surgery. Studies that compared perioperative steroids with other treatments or placebo were included. Study outcomes included postoperative back pain, leg pain, length of hospital stay, and return to work. Data was extracted through a proforma. Means and mean differences were calculated for continuous data, whereas odds ratios were calculated for dichotomous data. Data were analyzed with the help of Rev Man 5. Twenty RCTs were included in the review. Quantitative analysis could be performed on 19 RCTs. Intraoperative steroids improve control of back pain at 24-48 hours. Although there was some benefit of steroid administration in controlling postoperative leg pain, it disappeared at 1 year and in the overall pooled analysis. The length of hospital stay was much shorter in the steroid group. The frequency of adverse events and complications also favored steroid administration. Intraoperative epidural steroid administration offers some benefit in pain control with a significant reduction in the length of hospital stay. However, there is insufficient evidence to support the routine use of oral and intravenous steroids in the perioperative period.


Discrimination of methylated and nonmethylated region of a colorectal cancer related promoter using fluorescence enhancement of gold nanocluster at intrastrand of a 9C-loop.
Among epigenetic modifications of DNA, methylation of cytosine at its carbon 5 is the most common mark that is usually associated with gene silencing in human. Determining whether a particular DNA molecule is methylated or not, is an indispensable task in many epigenetic investigations. Presenting detection methods with less labor-intensive and time-consuming procedures has substantial value. Here a facile method based on gold nanocluster (AuNCs) fluorescence enhancement is presented. Target sequences were selected from Sept9 promoter region as its hypermethylation is demonstrated as a reliable biomarker of colorectal cancer. DNA probe was complementary to a 25 nucleotide of the target region and possessed 9 additional cytosines in the middle to allow the formation of AuNCs. Probe-AuNCs strands were first hybridized with methylated and non-methylated targets separately, and then their fluorescence intensities were recorded. Fluorescence intensity was higher with methylated targets than non-methylated one. Applying silver ions reversed the situation and fluorescence intensities of non-methylated DNA got higher than methylated one.


1400-million-year-old shale-facies microbiota from the lower belt supergroup, montana.
Carbonaceous shales of the Middle Proterozoic Newland Limestone, Belt Supergroup, Little Belt Mountains, Montana, contain abundant and well-preserved filamentous and spheroidal microfossils. The filamentous forms, ranging from less than 1 to 12 micrometers in width, are interpreted as representing the preserved sheaths of at least four species of nostocalean cyanophytes. The spheroidal forms, ranging from 15 to 108 micrometers in size, are evidently planktonic forms and are tentatively interpreted as representing the encystment stage of eukaryotic algae. The Newland microbiota is adaptable to petrographic thin-section work, and useful for evaluating the potential of such microfossils for intercontinental biostratigraphic correlation. It is the oldest shale-facies microbiota presently known from North America.


ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth.
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) is overexpressed in many types of cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in hepatocellular carcinoma (HCC). MAP4K4 expression was examined in 20 fresh HCCs and corresponding nontumor liver tissues. Immunohistochemistry for MAP4K4 was performed on additional 400 HCCs, of which 305 (76%) were positive for hepatitis B surface antigens. The clinical significance of MAP4K4 expression was analyzed. MAP4K4 downregulation was performed in HCC cell lines HepG2 and Hep3B with high abundance of MAP4K4, and the effects of MAP4K4 silencing on cell proliferation in vitro and tumor growth in vivo were evaluated. Quantitative real-time PCR arrays were employed to identify the MAP4K4-regulated signaling pathways. MAP4K4 was aberrantly overexpressed in HCCs relative to adjacent nontumor liver tissues. This overexpression was significantly associated with larger tumor size, increased histologic grade, advanced tumor stage, and intrahepatic metastasis, as well as worse overall survival and higher early recurrence rate. Knockdown of the MAP4K4 expression reduced cell proliferation, blocked cell cycle at S phase, and increased apoptosis. The antitumor effects of MAP4K4 silencing were also observed in vivo, manifested as retarded tumor xenograft growth. Furthermore, multiple tumor progression-related signaling pathways including JNK, NFκB, and toll-like receptors were repressed by MAP4K4 downregulation. MAP4K4 overexpression is an independent predictor of poor prognosis of HCC patients, and inhibition of its expression might be of therapeutic significance.


Interstitial high-dose-rate-brachytherapy in advanced esthesioneuroblastoma.
Esthesioneuroblastoma is a rare neuroectodermal tumor of the nasal vault with an aggressive biological behavior that is characterized by local recurrence, atypical distant metastasis, and poor long-term prognosis. The treatment regimen consists of surgical resection, radiation therapy, and chemotherapy in various, mainly stage-dependent, combinations. We report two cases of primary metastatic and locally recurrent disease, which were treated with computed tomography-guided interstitial high-dose-rate brachytherapy in palliative and curative intent, respectively. Computed tomography-guided interstitial high-dose-rate brachytherapy should be considered as a feasible treatment option for advanced esthesioneuroblastoma.


Pan-histone demethylase inhibitors simultaneously targeting Jumonji C and lysine-specific demethylases display high anticancer activities.
In prostate cancer, two different types of histone lysine demethylases (KDM), LSD1/KDM1 and JMJD2/KDM4, are coexpressed and colocalize with the androgen receptor. We designed and synthesized hybrid LSD1/JmjC or "pan-KDM" inhibitors 1-6 by coupling the skeleton of tranylcypromine 7, a known LSD1 inhibitor, with 4-carboxy-4'-carbomethoxy-2,2'-bipyridine 8 or 5-carboxy-8-hydroxyquinoline 9, two 2-oxoglutarate competitive templates developed for JmjC inhibition. Hybrid compounds 1-6 are able to simultaneously target both KDM families and have been validated as potential antitumor agents in cells. Among them, 2 and 3 increase H3K4 and H3K9 methylation levels in cells and cause growth arrest and substantial apoptosis in LNCaP prostate and HCT116 colon cancer cells. When tested in noncancer mesenchymal progenitor (MePR) cells, 2 and 3 induced little and no apoptosis, respectively, thus showing cancer-selective inhibiting action.


Adsorption Kinetics at Silica Gel/Ionic Liquid Solution Interface.
A series of imidazolium and pyridinium ionic liquids with different anions (Cl(-), Br(-), BF₄(-), PF₆(-)) has been evaluated for their adsorption activity on silica gel. Quantification of the ionic liquids has been performed by the use of RP-HPLC with organic-aqueous eluents containing an acidic buffer and a chaotropic salt. Pseudo-second order kinetic models were applied to the experimental data in order to investigate the kinetics of the adsorption process. The experimental data showed good fitting with this model, confirmed by considerably high correlation coefficients. The adsorption kinetic parameters were determined and analyzed. The relative error between the calculated and experimental amount of ionic liquid adsorbed at equilibrium was within 7%. The effect of various factors such as initial ionic liquid concentration, temperature, kind of solvent, kind of ionic liquid anion and cation on adsorption efficiency were all examined in a lab-scale study. Consequently, silica gel showed better adsorptive characteristics for imidazolium-based ionic liquids with chaotropic anions from aqueous solutions in comparison to pyridinium ionic liquids. The adsorption was found to decrease with the addition of organic solvents (methanol, acetonitrile) but it was not sensitive to the change of temperature in the range of 5-40 °C.


Intracellular calcium release through IP3R or RyR contributes to secondary axonal degeneration.
Severed CNS axons often retract or dieback away from the injury site and fail to regenerate. The precise mechanisms underlying acute axonal dieback and secondary axonal degeneration remain poorly understood. Here we investigate the role of Ca2+ store mediated intra-axonal Ca2+ release in acute axonal dieback and secondary axonal degeneration. To differentiate between primary (directly transected) and "bystander" axonal injury (axons spared by the initial injury but then succumb to secondary degeneration) in real-time we use our previously published highly focal laser-induced spinal cord injury (LiSCI) ex vivo model. Ascending spinal cord dorsal column axons that express YFP were severed using an 800 nm laser pulse while being imaged continuously using two-photon excitation microscopy. We inhibited two major intra-axonal Ca2+ store channels, ryanodine receptors (RyR) and IP3R, with ryanodine or 2-APB, respectively, to individually determine their role in axonal dieback and secondary axonal degeneration. Each antagonist was dissolved in artificial CSF and applied 1h post-injury alone or in combination, and continuously perfused for the remainder of the imaging session. Initially following LiSCI, transected axons retracted equal distances both distal and proximal to the lesion. However, by 4h after injury, the distal axonal segments that are destined for Wallerian degeneration had significantly retracted further than their proximal counterparts. We also found that targeting either RyR or IP3R using pharmacological and genetic approaches significantly reduced proximal axonal dieback and "bystander" secondary degeneration of axons compared to vehicle controls at 6h post-injury. Combined treatment effects on secondary axonal degeneration were similar to either drug in isolation. Together, these results suggest that intra-axonal Ca2+ store mediated Ca2+ release through RyR or IP3R contributes to secondary axonal degeneration following SCI.


Improving survival rate of Korean patients initiating dialysis.
The aim of this study was to investigate whether the survival rate among Korean dialysis patients changed during the period between 2005 and 2008 in Korea. A total of 32357 patients who began dialysis between January 1, 2005 and December 31, 2008 were eligible for analysis. Baseline demographics, comorbidities, and mortality data were obtained from the database of the Health Insurance Review & Assessment Service. Kaplan-Meier curves according to the year of dialysis initiation showed that the survival rate was significantly different (log-rank test, p=0.005), most notably among peritoneal dialysis (PD) patients (p<0.001), although not among hemodialysis (HD) patients (p=0.497). In multivariate analysis, however, patients initiating either HD or PD in 2008 also had a significantly lower risk of mortality compared to those who began dialysis in 2005. Subgroup survival analysis among patients initiating dialysis in 2008 revealed that the survival rate of PD patients was significantly higher than that of HD patients (p=0.001), and the survival benefit of PD over HD remained in non-diabetic patients aged less than 65 years after adjustment of covariates. Survival of Korean patients initiating dialysis from 2005 to 2008 has improved over time, particularly in PD patients. In addition, survival rates among patients initiating dialysis in 2008 were different according to patients' age and diabetes, thus we need to consider these factors when dialysis modality should be chosen.


The neurobiology and evolution of cannabinoid signalling.
The plant Cannabis sativa has been used by humans for thousands of years because of its psychoactivity. The major psychoactive ingredient of cannabis is Delta(9)-tetrahydrocannabinol, which exerts effects in the brain by binding to a G-protein-coupled receptor known as the CB1 cannabinoid receptor. The discovery of this receptor indicated that endogenous cannabinoids may occur in the brain, which act as physiological ligands for CB1. Two putative endocannabinoid ligands, arachidonylethanolamide ('anandamide') and 2-arachidonylglycerol, have been identified, giving rise to the concept of a cannabinoid signalling system. Little is known about how or where these compounds are synthesized in the brain and how this relates to CB1 expression. However, detailed neuroanatomical and electrophysiological analysis of mammalian nervous systems has revealed that the CB1 receptor is targeted to the presynaptic terminals of neurons where it acts to inhibit release of 'classical' neurotransmitters. Moreover, an enzyme that inactivates endocannabinoids, fatty acid amide hydrolase, appears to be preferentially targeted to the somatodendritic compartment of neurons that are postsynaptic to CB1-expressing axon terminals. Based on these findings, we present here a model of cannabinoid signalling in which anandamide is synthesized by postsynaptic cells and acts as a retrograde messenger molecule to modulate neurotransmitter release from presynaptic terminals. Using this model as a framework, we discuss the role of cannabinoid signalling in different regions of the nervous system in relation to the characteristic physiological actions of cannabinoids in mammals, which include effects on movement, memory, pain and smooth muscle contractility. The discovery of the cannabinoid signalling system in mammals has prompted investigation of the occurrence of this pathway in non-mammalian animals. Here we review the evidence for the existence of cannabinoid receptors in non-mammalian vertebrates and invertebrates and discuss the evolution of the cannabinoid signalling system. Genes encoding orthologues of the mammalian CB1 receptor have been identified in a fish, an amphibian and a bird, indicating that CB1 receptors may occur throughout the vertebrates. Pharmacological actions of cannabinoids and specific binding sites for cannabinoids have been reported in several invertebrate species, but the molecular basis for these effects is not known. Importantly, however, the genomes of the protostomian invertebrates Drosophila melanogaster and Caenorhabditis elegans do not contain CB1 orthologues, indicating that CB1-like cannabinoid receptors may have evolved after the divergence of deuterostomes (e.g. vertebrates and echinoderms) and protostomes. Phylogenetic analysis of the relationship of vertebrate CB1 receptors with other G-protein-coupled receptors reveals that the paralogues that appear to share the most recent common evolutionary origin with CB1 are lysophospholipid receptors, melanocortin receptors and adenosine receptors. Interestingly, as with CB1, each of these receptor types does not appear to have Drosophila orthologues, indicating that this group of receptors may not occur in protostomian invertebrates. We conclude that the cannabinoid signalling system may be quite restricted in its phylogenetic distribution, probably occurring only in the deuterostomian clade of the animal kingdom and possibly only in vertebrates.


Prevalence of parental supply of alcohol to minors: a systematic review.
Parental supply of alcohol to minors (i.e. those under the legal drinking age) is often perceived by parents as protective against harms from drinking, despite evidence linking it with adverse alcohol-related outcomes. This systematic review describes the prevalence of parental supply of alcohol, as reported in the international literature. The review was registered with PROSPERO (CRD42020218754). We searched seven online databases (Medline, Embase, PsycINFO, CINAHL, Scopus, Web of Science and Public Health Database) and grey literature from January 2011 to December 2022 and assessed the risk of bias with the JBI Critical Appraisal Checklist. Among 58 articles included in narrative synthesis from 29 unique datasets, there was substantial variation in the definition and measurement of parental supply of alcohol. Overall prevalence rates ranged from 7.0 to 60.0% for minor-report samples, and from 24.0 to 8.0% for parent-report samples. Data indicate that parental supply prevalence is generally proportionately higher for older minors or later-stage students, for girls, and has increased over time among minors who report drinking. Literature on the prevalence of parental supply of alcohol is robust in quantity but inconsistent in quality and reported prevalence. Greater consistency in defining and measuring parental supply is needed to better inform health promotion initiatives aimed at increasing parents' awareness.


Optimizing pentacene thin-film transistor performance: Temperature and surface condition induced layer growth modification.
In this work we present in situ electrical and surface analytical, as well as ex situ atomic force microscopy (AFM) studies on temperature and surface condition induced pentacene layer growth modifications, leading to the selection of optimized deposition conditions and entailing performance improvements. We prepared p++-silicon/silicon dioxide bottom-gate, gold bottom-contact transistor samples and evaluated the pentacene layer growth for three different surface conditions (sputtered, sputtered + carbon and unsputtered + carbon) at sample temperatures during deposition of 200 K, 300 K and 350 K. The AFM investigations focused on the gold contacts, the silicon dioxide channel region and the highly critical transition area. Evaluations of coverage dependent saturation mobilities, threshold voltages and corresponding AFM analysis were able to confirm that the first 3-4 full monolayers contribute to the majority of charge transport within the channel region. At high temperatures and on sputtered surfaces uniform layer formation in the contact-channel transition area is limited by dewetting, leading to the formation of trenches and the partial development of double layer islands within the channel region instead of full wetting layers. By combining the advantages of an initial high temperature deposition (well-ordered islands in the channel) and a subsequent low temperature deposition (continuous film formation for low contact resistance) we were able to prepare very thin (8 ML) pentacene transistors of comparably high mobility.


Palm oil and human health. Meeting report of NFI: Nutrition Foundation of Italy symposium.
The use of palm oil by the food industry is increasingly criticized, especially in Italy, for its purported negative effects on human health and environment. This paper summarizes the conclusions of a Symposium on this topic, gathered by the Nutrition Foundation of Italy, among experts representing a number of Italian Medical and Nutritional Scientific Societies. Toxicological and environmental issues were not considered. Participants agreed that: no evidence does exist on the specific health effects of palm oil consumption as compared to other saturated fatty acids-rich fats; the stereospecific distribution of saturated fatty acids in the triacylglycerol molecule of palm oil limits their absorption rate and metabolic effects; in agreement with International guidelines, saturated fatty acids intake should be kept <10% of total energy, within a balanced diet; within these limits, no effect of palm oil consumption on human health (and specifically on CVD or cancer risk) can be foreseen.


From bathymetry to bioshields: a review of post-tsunami ecological research in India and its implications for policy.
More than half a decade has passed since the December 26th 2004 tsunami hit the Indian coast leaving a trail of ecological, economic and human destruction in its wake. We reviewed the coastal ecological research carried out in India in the light of the tsunami. In addition, we also briefly reviewed the ecological research in other tsunami affected countries in Asia namely Sri Lanka, Indonesia, Thailand and Maldives in order to provide a broader perspective of ecological research after tsunami. A basic search in ISI Web of Knowledge using keywords "tsunami" and "India" resulted in 127 peer reviewed journal articles, of which 39 articles were pertaining to ecological sciences. In comparison, Sri Lanka, Indonesia, Thailand and Maldives had, respectively, eight, four, 21 and two articles pertaining to ecology. In India, bioshields received the major share of scientific interest (14 out of 39) while only one study (each) was dedicated to corals, seagrasses, seaweeds and meiofauna, pointing to the paucity of research attention dedicated to these critical ecosystems. We noted that very few interdisciplinary studies looked at linkages between pure/applied sciences and the social sciences in India. In addition, there appears to be little correlation between the limited research that was done and its influence on policy in India. This review points to gap areas in ecological research in India and highlights the lessons learnt from research in other tsunami-affected countries. It also provides guidance on the links between science and policy that are required for effective coastal zone management.


Cell cycle timing regulation during asynchronous divisions of the early C. elegans embryo.
A fundamental question in developmental biology is how different cell lineages acquire different cell cycle durations. With its highly stereotypical asymmetric and asynchronous cell divisions, the early Caenorhabditis elegans embryo provides an ideal system to study lineage-specific cell cycle timing regulation during development, with high spatio-temporal resolution. The first embryonic division is asymmetric and generates two blastomeres of different sizes (AB>P1) and developmental potentials that divide asynchronously, with the anterior somatic blastomere AB dividing reproducibly two minutes before the posterior germline blastomere P1. The evolutionarily conserved PAR proteins (abnormal embryonic PARtitioning of cytoplasm) regulate all of the asymmetries in the early embryo including cell cycle asynchrony between AB and P1 blastomeres. Here we discuss our current understanding and open questions on the mechanism by which the PAR proteins regulate asynchronous cell divisions in the early C. elegans embryo.


Spiral ganglion degeneration and hearing loss as a consequence of satellite cell death in saposin B-deficient mice.
Saposin B (Sap B) is an essential activator protein for arylsulfatase A in the hydrolysis of sulfatide, a lipid component of myelin. To study Sap B's role in hearing and balance, a Sap B-deficient (B(-/-)) mouse was evaluated. At both light and electron microscopy (EM) levels, inclusion body accumulation was seen in satellite cells surrounding spiral ganglion (SG) neurons from postnatal month 1 onward, progressing into large vacuoles preceding satellite cell degeneration, and followed by SG degeneration. EM also revealed reduced or absent myelin sheaths in SG neurons from postnatal month 8 onwards. Hearing loss was initially seen at postnatal month 6 and progressed thereafter for frequency-specific stimuli, whereas click responses became abnormal from postnatal month 13 onward. The progressive hearing loss correlated with the accumulation of inclusion bodies in the satellite cells and their subsequent degeneration. Outer hair cell numbers and efferent function measures (distortion product otoacoustic emissions and contralateral suppression) were normal in the B(-/-) mice throughout this period. Alcian blue staining of SGs demonstrated that these inclusion bodies corresponded to sulfatide accumulation. In contrast, changes in the vestibular system were much milder, but caused severe physiologic deficits. These results demonstrate that loss of Sap B function leads to progressive sulfatide accumulation in satellite cells surrounding the SG neurons, leading to satellite cell degeneration and subsequent SG degeneration with a resultant loss of hearing. Relative sparing of the efferent auditory and vestibular neurons suggests that alternate glycosphingolipid metabolic pathways predominate in these other systems.


One nutritional symbiosis begat another: phylogenetic evidence that the ant tribe Camponotini acquired Blochmannia by tending sap-feeding insects.
Bacterial endosymbiosis has a recurring significance in the evolution of insects. An estimated 10-20% of insect species depend on bacterial associates for their nutrition and reproductive viability. Members of the ant tribe Camponotini, the focus of this study, possess a stable, intracellular bacterial mutualist. The bacterium, Blochmannia, was first discovered in Camponotus and has since been documented in a distinct subgenus of Camponotus, Colobopsis, and in the related genus Polyrhachis. However, the distribution of Blochmannia throughout the Camponotini remains in question. Documenting the true host range of this bacterial mutualist is an important first step toward understanding the various ecological contexts in which it has evolved, and toward identifying its closest bacterial relatives. In this study, we performed a molecular screen, based on PCR amplification of 16S rDNA, to identify bacterial associates of diverse Camponotini species. Phylogenetic analyses of 16S rDNA gave four important insights: (i) Blochmannia occurs in a broad range of Camponotini genera including Calomyrmex, Echinopla, and Opisthopsis, and did not occur in outgroups related to this tribe (e.g., Notostigma). This suggests that the mutualism originated in the ancestor of the tribe Camponotini. (ii) The known bacteriocyte-associated symbionts of ants, in Formica, Plagiolepis, and the Camponotini, arose independently. (iii) Blochmannia is nestled within a diverse clade of endosymbionts of sap-feeding hemipteran insects, such as mealybugs, aphids, and psyllids. In our analyses, a group of secondary symbionts of mealybugs are the closest relatives of Blochmannia. (iv) Blochmannia has cospeciated with its known hosts, although deep divergences at the genus level remain uncertain. The Blochmannia mutualism occurs in Calomyrmex, Echinopla, and Opisthopsis, in addition to Camponotus, and probably originated in the ancestral lineage leading to the Camponotini. This significant expansion of its known host range implies that the mutualism is more ancient and ecologically diverse than previously documented. Blochmannia is most closely related to endosymbionts of sap-feeding hemipterans, which ants tend for their carbohydrate-rich honeydew. Based on phylogenetic results, we propose Camponotini might have originally acquired this bacterial mutualist through a nutritional symbiosis with other insects.


Drug information resources used by nurse practitioners and collaborating physicians at the point of care in Nova Scotia, Canada: a survey and review of the literature.
Keeping current with drug therapy information is challenging for health care practitioners. Technologies are often implemented to facilitate access to current and credible drug information sources. In the Canadian province of Nova Scotia, legislation was passed in 2002 to allow nurse practitioners (NPs) to practice collaboratively with physician partners. The purpose of this study was to determine the current utilization patterns of information technologies by these groups of practitioners. Nurse practitioners and their collaborating physician partners in Nova Scotia were sent a survey in February 2005 to determine the frequency of use, usefulness, accessibility, credibility, and current/timeliness of personal digital assistant (PDA), computer, and print drug information resources. Two surveys were developed (one for PDA users and one for computer users) and revised based on a literature search, stakeholder consultation, and pilot-testing results. A second distribution to nonresponders occurred two weeks following the first. Data were entered and analysed with SPSS. Twenty-seven (14 NPs and 13 physicians) of 36 (75%) recipients responded. 22% (6) returned personal digital assistant (PDA) surveys. Respondents reported print, health professionals, and online/electronic resources as the most to least preferred means to access drug information, respectively. 37% and 35% of respondents reported using "both print and electronic but print more than electronic" and "print only", respectively, to search monograph-related drug information queries whereas 4% reported using "PDA only". Analysis of respondent ratings for all resources in the categories print, health professionals and other, and online/electronic resources, indicated that the Compendium of Pharmaceuticals and Specialties and pharmacists ranked highly for frequency of use, usefulness, accessibility, credibility, and current/timeliness by both groups of practitioners. Respondents' preferences and resource ratings were consistent with self-reported methods for conducting drug information queries. Few differences existed between NP and physician rankings of resources. The use of computers and PDAs remains limited, which is also consistent with preferred and frequent use of print resources. Education for these practitioners regarding available electronic drug information resources may facilitate future computer and PDA use. Further research is needed to determine methods to increase computer and PDA use and whether these technologies affect prescribing and patient outcomes.


CREB signaling--timing is everything.
Depolarization of neurons can lead to changes in gene expression that are important for such processes as synaptic plasticity, neuronal differentiation, and apoptosis. Impey and Goodman discuss some of the opposing models for how gene transcription in response to neuronal activity and elevations in intracellular calcium concentration is regulated. The pathways appear to converge on cyclic AMP response element-binding (CREB) protein, with the mitogen-activated protein kinase pathways playing an important role. The continuing debate about the involvement of calmodulin kinase IV is also described.


Herpes zoster in Australia: evidence of increase in incidence in adults attributable to varicella immunization?
Rates of herpes zoster (HZ) hospitalizations, antiviral prescriptions, and New South Wales emergency-department presentations for age groups <20, 20-39, 40-59 and ⩾60 years were investigated. Trends were analysed using Poisson regression to determine if rates increased following funding of varicella immunization in Australia in November 2005. The regression analysis revealed significantly increasing trends of between 2% and 6% per year in both antiviral prescriptions and emergency-department presentations in all except the <20 years age group. When considered together, the differential changes in rates observed by age group provides preliminary evidence to indicate that HZ incidence is increasing in adults aged >20 years. However, it is not possible to attribute the increasing trends in HZ observed directly to the varicella immunization programme, and continued monitoring and analyses of data for a longer duration, both pre- and post-vaccine introduction, is required.


Stage-specific keratins in Xenopus laevis embryos and tadpoles: the XK81 gene family.
This report describes the isolation and characterization of genomic and cDNA clones which define a subfamily of type I keratins in Xenopus laevis whose expression is restricted to embryonic and larval stages. The XK81 subfamily, named after the prototype cDNA clone DG81, contains four members arranged in two pairs of closely homologous loci; they were named 81A1, A2, B1, and B2. Genomic clones were obtained representing all of these regions. The A1 gene has been completely sequenced together with approximately 1 kb of flanking sequences at each end; this gene corresponds to the previously reported cDNA clone 8128 (Jonas, E., T. D. Sargent, and I. B. Dawid, 1985, Proc. Natl. Acad. Sci. USA, 82:5413-5417). The B2 gene is represented by a partial cDNA clone, DG118. Upstream sequences and about half of the coding regions have been sequenced for the B1 and B2 genes, whereas the A2 locus has been identified on the basis of hybridization data and could be a gene or pseudogene. Genomic Southern blotting indicates that all members of the subfamily have been isolated. The keratin proteins encoded by the B1 and B2 genes are 96% homologous in the central rod domain, whereas A/B gene homology in this region is 81%. During development mRNAs derived from A and B genes accumulate coordinately during gastrula and neurula stages; in the tadpole, 81A mRNA decays rapidly, whereas 81B mRNA shows a second abundance peak, persists for most of tadpole life, and decays by metamorphosis. RNAs derived from the XK81 keratin subfamily are undetectable in the adult, where different type I keratin genes are expressed.


Antiadhesive properties of arabinogalactan protein from ribes nigrum seeds against bacterial adhesion of Helicobacter pylori.
Fruit extracts from black currants (Ribes nigrum L.) are traditionally used for treatment of gastritis based on seed polysaccharides that inhibit the adhesion of Helicobacter pylori to stomach cells. For detailed investigations an arabinogalactan protein (F2) was isolated from seeds and characterized concerning molecular weight, carbohydrate, amino acid composition, linkage, configuration and reaction with β-glucosyl Yariv. Functional testing of F2 was performed by semiquantitative in situ adhesion assay on sections of human gastric mucosa and by quantitative in vitro adhesion assay with FITC-labled H. pylori strain J99 and human stomach AGS cells. Bacterial adhesins affected were identified by overlay assay with immobilized ligands. ¹²⁵I-radiolabeled F2 served for binding studies to H. pylori and interaction experiments with BabA and SabA. F2 had no cytotoxic effects against H. pylori and AGS cells; but inhibited bacterial binding to human gastric cells. F2 inhibited the binding of BabA and fibronectin-binding adhesin to its specific ligands. Radiolabeled F2 bound non-specifically to different strains of H. pylori; and to BabA deficient mutant. F2 did not lead to subsequent feedback regulation or increased expression of adhesins or virulence factors. From these data the non-specific interactions between F2 and the H. pylori lead to moderate antiadhesive effects.


Maternal preconception weight trajectories, pregnancy complications and offspring's childhood physical and cognitive development.
There is limited evidence on the association between maternal preconception body mass index (BMI) trajectories and pregnancy complications and child development. This study examined the relationships of maternal BMI trajectories, diabetes and hypertensive disorders during pregnancy and offspring's childhood physical and cognitive development. Data were from the Australian Longitudinal Study on Women's Health and the Mothers and their Children's Health study (n=771). Women's preconception BMI trajectories were identified using group-based trajectory modelling. Children's physical and cognitive development (up to the average age of 5 years) were obtained from the Ages and Stages Questionnaire (suspected gross motor delay) and the Australian Early Development Census (AEDC). Generalized estimating equation models, adjusted for maternal sociodemographic and lifestyle factors, were used for analyses. Three distinct BMI trajectories were identified (normative, chronically overweight and chronically obese). Children born to chronically obese women were more likely to be classified as developmentally vulnerable/at-risk on AEDC domains; gross and fine motor skills [risk ratio (RR)=1.64, 95% confidence interval (CI): 1.04, 2.61] and communication skills and general knowledge (RR=1.71, 95% CI: 1.09, 2.68). They also had an elevated risk of suspected gross motor delay (RR=2.62, 95% CI: 1.26, 5.44) compared with children born to women with a normative BMI trajectory. Maternal diabetes or hypertensive disorders during pregnancy were not associated with child outcomes. Maternal preconception BMI trajectories were associated with poorer childhood development. This study finding underscores the importance of excessive weight gain prevention throughout the reproductive stage of life.


Plasticity of the aging brain: new directions in cognitive neuroscience.
Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span.


Telementoring of primary care providers delivering hepatitis C treatment in New York City: Results from Project INSPIRE.
The recent availability of highly effective, easily administered, and relatively nontoxic treatments for hepatitis C virus (HCV) infection provides an opportunity for clinicians to treat HCV in nonspecialist settings with appropriate support. Project INSPIRE provides care coordination to HCV patients and a web-based training program (telementoring) on disease management and treatment by HCV specialists to primary care providers inexperienced in HCV treatment. Weekly telementoring sessions use a didactic and case-based approach to instruct non-HCV providers on how to identify and assess HCV treatment candidates and prescribe appropriate treatment. We used mixed methods to assess the telementoring service, including provider surveys and semistructured interviews. Quantitative data were analyzed using descriptive statistics, and qualitative data were analyzed to identify dominant themes. Provider survey responses indicated an increased ability to identify and evaluate HCV treatment candidates and increased confidence in sharing knowledge with peers and patients. Interviews revealed a high degree of satisfaction with the telementoring service and Project INSPIRE overall. The telementoring service was viewed as having enhanced providers' knowledge, confidence, and ability to treat their own HCV-infected patients rather than having to refer them to an HCV specialist with resulting benefits for continuity of care. Providers reported comradery and collegiality with other INSPIRE providers and satisfaction with professional growth from attaining new knowledge and skills via the telementoring service. Using readily available web conferencing technology, telementoring can facilitate knowledge transfer between specialists and primary care providers, facilitating continuity of care for patients and increased provider satisfaction.


Tbx3 is a downstream target of the Wnt/beta-catenin pathway and a critical mediator of beta-catenin survival functions in liver cancer.
Tbx3 encodes a transcriptional repressor that is important for diverse patterning events during development, and Tbx3 mutation in humans causes the ulnar-mammary syndrome. Here, we describe the identification of Tbx3 in array-based search for genes downstream Wnt/beta-catenin that are implicated in liver tumorigenesis. Overexpression of Tbx3 is closely associated with the mutational status of beta-catenin in murine liver tumors induced by Myc as well as in human hepatocellular carcinomas and hepatoblastomas. Moreover, Tbx3 transcription is activated by ectopic expression of beta-catenin in mouse liver and in human tumor cell lines. Evidence that Tbx3 transcription is directly regulated by beta-catenin is provided by chromatin immunoprecipitation and reporter assays. Although HepG2 cells stably transfected with Tbx3 display moderately enhanced growth rate, the dominant negative mutant Tbx3-Y149S drastically inhibits hepatoma cell growth in vitro and in vivo. Moreover, small interfering RNAs (siRNA) directed against Tbx3 inhibit anchorage-independent growth of liver and colon carcinoma cells. We further show that inhibition of Tbx3 expression by specific siRNAs blocks beta-catenin-mediated cell survival and renders cells sensitive to doxorubicin-induced apoptosis. Conversely, ectopic expression of Tbx3 inhibits apoptosis induced by beta-catenin depletion. Marked overexpression of Tbx3 in a subset of hepatoblastomas is associated with chemotherapy-resistant phenotype and unfavorable patient outcome. These results reveal an unsuspected role of Tbx3 as a mediator of beta-catenin activities on cell proliferation and survival and as an important player in liver tumorigenesis.


Mapping and validation of the major sex-determining region in Nile tilapia (Oreochromis niloticus L.) Using RAD sequencing.
Sex in Oreochromis niloticus (Nile tilapia) is principally determined by an XX/XY locus but other genetic and environmental factors also influence sex ratio. Restriction Associated DNA (RAD) sequencing was used in two families derived from crossing XY males with females from an isogenic clonal line, in order to identify Single Nucleotide Polymorphisms (SNPs) and map the sex-determining region(s). We constructed a linkage map with 3,802 SNPs, which corresponded to 3,280 informative markers, and identified a major sex-determining region on linkage group 1, explaining nearly 96% of the phenotypic variance. This sex-determining region was mapped in a 2 cM interval, corresponding to approximately 1.2 Mb in the O. niloticus draft genome. In order to validate this, a diverse family (4 families; 96 individuals in total) and population (40 broodstock individuals) test panel were genotyped for five of the SNPs showing the highest association with phenotypic sex. From the expanded data set, SNPs Oni23063 and Oni28137 showed the highest association, which persisted both in the case of family and population data. Across the entire dataset all females were found to be homozygous for these two SNPs. Males were heterozygous, with the exception of five individuals in the population and two in the family dataset. These fish possessed the homozygous genotype expected of females. Progeny sex ratios (over 95% females) from two of the males with the "female" genotype indicated that they were neomales (XX males). Sex reversal induced by elevated temperature during sexual differentiation also resulted in phenotypic males with the "female" genotype. This study narrows down the region containing the main sex-determining locus, and provides genetic markers tightly linked to this locus, with an association that persisted across the population. These markers will be of use in refining the production of genetically male O. niloticus for aquaculture.


The prevalence and identification of risk factors for NIDDM in urban Africans in Cape Town, South Africa.
To determine the prevalence of NIDDM and associated risk factors in urban Africans in Cape Town, South Africa. With a three-stage, proportional, stratified, random cluster method, we sampled 1000 Africans, > 30 yr of age, living in African residential areas in Cape Town. We assessed glucose tolerance with a 75-g oral glucose tolerance test, according to World Health Organization criteria, and obtained anthropometric and demographic data. The response rate was 79%. The prevalence of NIDDM was 8.0% (confidence interval 5.8-10.3%), age-adjusted to world population figures and that of impaired glucose tolerance, 7.0% (confidence interval 4.9-9.1%). Multivariate analysis indicated that increased age (odds ratio 4.18), upper-segment fat distribution (odds ratio 2.94), proportion of life spent in an urban area (odds ratio 2.32), and obesity (odds ratio 2.31) were significant independent risk factors for NIDDM. In contrast, sex, family history, alcohol intake, and physical activity were not independent risk factors. Only increased age (odds ratio 4.06) was a significant risk factor for impaired glucose tolerance. The prevalence of NIDDM in urban Africans in Cape Town, South Africa, is moderately high, and considerably higher than previous reports from Africa. The association of NIDDM with urbanization has important implications in view of the large-scale urbanization occurring in southern Africa.


Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a serious systemic autoimmune disorder that affects multiple organ systems and is characterized by unpredictable flares of disease. Recent evidence indicates a role for type I interferon (IFN) in SLE pathogenesis; however, the downstream effects of IFN pathway activation are not well understood. Here we test the hypothesis that type I IFN-regulated proteins are present in the serum of SLE patients and correlate with disease activity. We performed a comprehensive survey of the serologic proteome in human SLE and identified dysregulated levels of 30 cytokines, chemokines, growth factors, and soluble receptors. Particularly striking was the highly coordinated up-regulation of 12 inflammatory and/or homeostatic chemokines, molecules that direct the movement of leukocytes in the body. Most of the identified chemokines were inducible by type I IFN, and their levels correlated strongly with clinical and laboratory measures of disease activity. These data suggest that severely disrupted chemokine gradients may contribute to the systemic autoimmunity observed in human SLE. Furthermore, the levels of serum chemokines may serve as convenient biomarkers for disease activity in lupus.


Stabilizing Leaf and Branch Compost Cutinase (LCC) with Glycosylation: Mechanism and Effect on PET Hydrolysis.
Cutinases are polyester hydrolases that show a remarkable capability to hydrolyze polyethylene terephthalate (PET) to its monomeric units. This revelation has stimulated research aimed at developing sustainable and green cutinase-catalyzed PET recycling methods. Leaf and branch compost cutinase (LCC) is particularly suited toward these ends given its relatively high PET hydrolysis activity and thermostability. Any practical enzymatic PET recycling application will require that the protein have kinetic stability at or above the PET glass transition temperature (Tg, i.e., 70 °C). This paper elucidates the thermodynamics and kinetics of LCC conformational and colloidal stability. Aggregation emerged as a major contributor that reduces LCC kinetic stability. In its native state, LCC is prone to aggregation owing to electrostatic interactions. Further, with increasing temperature, perturbation of LCC's tertiary structure and corresponding exposure of hydrophobic domains leads to rapid aggregation. Glycosylation was employed in an attempt to impede LCC aggregation. Owing to the presence of three putative N-glycosylation sites, expression of native LCC in Pichia pastoris resulted in the production of glycosylated LCC (LCC-G). LCC-G showed improved stability to native state aggregation while increasing the temperature for thermal induced aggregation by 10 °C. Furthermore, stabilization against thermal aggregation resulted in improved catalytic PET hydrolysis both at its optimum temperature and concentration.


Electrochemical impedance spectroscopy investigations of a microelectrode behavior in a thin-layer cell: Experimental and theoretical studies.
Electrochemical impedance spectroscopy experiments were performed on a microdisk electrode in a thin-layer cell using a scanning electrochemical microscope for controlling the cell geometry. Experimental data showed that when the thin-layer thickness diminished, an additional low-frequency response appeared. It was ascribed to the radial diffusion of the electroactive species and was strongly dependent on the thin-layer dimensions (both thickness and diameter). Moreover, the numerical simulation of the impedance diagrams by finite element method calculations confirmed this behavior. An equivalent circuit based on a Randles-type circuit was proposed. Thus, the diffusion was described by introducing two electrical elements: one for the spherical diffusion and the other for the radial contribution. A nonlinear Simplex algorithm was used, and this circuit was shown to fit the impedance diagrams with a good accuracy.


Relationship between healthy diet and risk of cardiovascular disease among patients on drug therapies for secondary prevention: a prospective cohort study of 31 546 high-risk individuals from 40 countries.
Diet quality is strongly related to cardiovascular disease (CVD) incidence, but little is known about its impact on CVD events in older people at high risk of CVD and receiving effective drugs for secondary prevention. This study assessed the association between diet quality and CVD events in a large population of subjects from 40 countries with CVD or diabetes mellitus with end-organ damage receiving proven medications. Overall, 31 546 women and men 66.5±6.2 years of age enrolled in 2 randomized trials, the Ongoing Telmisartan Alone and in Combination With Ramipril Global End Point Trial (ONTARGET) and the Telmisartan Randomized Assessment Study in ACEI Intolerant Subjects With Cardiovascular Disease (TRANSCEND), were studied. We used 2 dietary indexes: the modified Alternative Healthy Eating Index and the Diet Risk Score. The association between diet quality and the primary composite outcome of CV death, myocardial infarction, stroke, or congestive heart failure was assessed with Cox proportional hazard regression with adjustment for age, sex, trial enrollment allocation, region, and other known confounders. During the 56-month follow-up, there were 5190 events. Patients in the healthier quintiles of modified Alternative Healthy Eating Index scores had a significantly lower risk of CVD (hazard ratio, 0.78; 95% confidence interval, 0.71-0.87, top versus lowest quintile of modified Alternative Healthy Eating Index). The reductions in risk for CV death, myocardial infarction, and stroke were 35%, 14%, and 19%, respectively. The protective association was consistent regardless of whether patients were receiving proven drugs. A higher-quality diet was associated with a lower risk of recurrent CVD events among people ≥55 years of age with CVD or diabetes mellitus. Highlighting the importance of healthy eating by health professionals would substantially reduce CVD recurrence and save lives globally.


Soy food consumption is associated with lower risk of coronary heart disease in Chinese women.
Soy food intake has been shown to have beneficial effects on cardiovascular disease risk factors. Data directly linking soy food intake to clinical outcomes of cardiovascular disease, however, are sparse. We examined the relationship between soy food intake and incidence of coronary heart disease (CHD) among participants in the Shanghai Women's Health Study, a population-based prospective cohort study of approximately 75000 Chinese women aged 40-70 y at the baseline survey that was conducted from 1997 to 2000. Included in this study were 64915 women without previously diagnosed CHD, stroke, cancer and diabetes at baseline. Information on usual intake of soy foods was obtained at baseline through an in-person interview using a validated food-frequency questionnaire. Cohort members were followed biennially through in-person interviews. After a mean of 2.5 y (162277 person-years) of follow-up, 62 incident cases of CHD (43 nonfatal myocardial infarctions and 19 CHD deaths) were documented. There was a clear monotonic dose-response relationship between soy food intake and risk of total CHD (P for trend = 0.003) with an adjusted relative risk (RR) of 0.25 (95% CI, 0.10-0.63) observed for women in the highest vs. the lowest quartile of total soy protein intake. The inverse association was more pronounced for nonfatal myocardial infarction (RR = 0.14; 95% CI, 0.04-0.48 for the highest vs. the lowest quartile of intake; P for trend = 0.001). This study provides, for the first time, direct evidence that soy food consumption may reduce the risk of CHD in women.


Personalised care planning for adults with chronic or long-term health conditions.
Personalised care planning is a collaborative process used in chronic condition management in which patients and clinicians identify and discuss problems caused by or related to the patient's condition, and develop a plan for tackling these. In essence it is a conversation, or series of conversations, in which they jointly agree goals and actions for managing the patient's condition. To assess the effects of personalised care planning for adults with long-term health conditions compared to usual care (i.e. forms of care in which active involvement of patients in treatment and management decisions is not explicitly attempted or achieved). We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO, ProQuest, clinicaltrials.gov and WHO International Clinical Trials Registry Platform to July 2013. We included randomised controlled trials and cluster-randomised trials involving adults with long-term conditions where the intervention included collaborative (between individual patients and clinicians) goal setting and action planning. We excluded studies where there was little or no opportunity for the patient to have meaningful influence on goal selection, choice of treatment or support package, or both. Two of three review authors independently screened citations for inclusion, extracted data, and assessed risk of bias. The primary outcomes were effects on physical health, psychological health, subjective health status, and capabilities for self management. Secondary outcomes included effects on health-related behaviours, resource use and costs, and type of intervention. A patient advisory group of people with experience of living with long-term conditions advised on various aspects of the review, including the protocol, selection of outcome measures and emerging findings. We included 19 studies involving a total of 10,856 participants. Twelve of these studies focused on diabetes, three on mental health, one on heart failure, one on end-stage renal disease, one on asthma, and one on various chronic conditions. All 19 studies included components that were intended to support behaviour change among patients, involving either face-to-face or telephone support. All but three of the personalised care planning interventions took place in primary care or community settings; the remaining three were located in hospital clinics. There was some concern about risk of bias for each of the included studies in respect of one or more criteria, usually due to inadequate or unclear descriptions of research methods. Physical healthNine studies measured glycated haemoglobin (HbA1c), giving a combined mean difference (MD) between intervention and control of -0.24% (95% confidence interval (CI) -0.35 to -0.14), a small positive effect in favour of personalised care planning compared to usual care (moderate quality evidence).Six studies measured systolic blood pressure, a combined mean difference of -2.64 mm/Hg (95% CI -4.47 to -0.82) favouring personalised care (moderate quality evidence). The pooled results from four studies showed no significant effect on diastolic blood pressure, MD -0.71 mm/Hg (95% CI -2.26 to 0.84).We found no evidence of an effect on cholesterol (LDL-C), standardised mean difference (SMD) 0.01 (95% CI -0.09 to 0.11) (five studies) or body mass index, MD -0.11 (95% CI -0.35 to 0.13) (four studies).A single study of people with asthma reported that personalised care planning led to improvements in lung function and asthma control. Psychological healthSix studies measured depression. We were able to pool results from five of these, giving an SMD of -0.36 (95% CI -0.52 to -0.20), a small effect in favour of personalised care (moderate quality evidence). The remaining study found greater improvement in the control group than the intervention group.Four other studies used a variety of psychological measures that were conceptually different so could not be pooled. Of these, three found greater improvement for the personalised care group than the usual care group and one was too small to detect differences in outcomes. Subjective health statusTen studies used various patient-reported measures of health status (or health-related quality of life), including both generic health status measures and condition-specific ones. We were able to pool data from three studies that used the SF-36 or SF-12, but found no effect on the physical component summary score SMD 0.16 (95% CI -0.05 to 0.38) or the mental component summary score SMD 0.07 (95% CI -0.15 to 0.28) (moderate quality evidence). Of the three other studies that measured generic health status, two found improvements related to personalised care and one did not.Four studies measured condition-specific health status. The combined results showed no difference between the intervention and control groups, SMD -0.01 (95% CI -0.11 to 0.10) (moderate quality evidence). Self-management capabilitiesNine studies looked at the effect of personalised care on self-management capabilities using a variety of outcome measures, but they focused primarily on self efficacy. We were able to pool results from five studies that measured self efficacy, giving a small positive result in favour of personalised care planning: SMD 0.25 (95% CI 0.07 to 0.43) (moderate quality evidence).A further five studies measured other attributes that contribute to self-management capabilities. The results from these were mixed: two studies found evidence of an effect on patient activation, one found an effect on empowerment, and one found improvements in perceived interpersonal support. Other outcomesPooled data from five studies on exercise levels showed no effect due to personalised care planning, but there was a positive effect on people's self-reported ability to carry out self-care activities: SMD 0.35 (95% CI 0.17 to 0.52).We found no evidence of adverse effects due to personalised care planning.The effects of personalised care planning were greater when more stages of the care planning cycle were completed, when contacts between patients and health professionals were more frequent, and when the patient's usual clinician was involved in the process. Personalised care planning leads to improvements in certain indicators of physical and psychological health status, and people's capability to self-manage their condition when compared to usual care. The effects are not large, but they appear greater when the intervention is more comprehensive, more intensive, and better integrated into routine care.


A comparison of perceptions of nuts between the general public, dietitians, general practitioners, and nurses.
Nut consumption at the population level remains low despite the well-documented benefits of their consumption, including their cardioprotective effects. Studies have suggested that advice from health professionals may be a means to increase nut consumption levels. Understanding how nuts are perceived by the public and health professionals, along with understanding the public's perceptions of motivators of and deterrents to consuming nuts, may inform the development of initiatives to improve on these low levels of consumption. The aim of this cross-sectional study was to compare perceptions of nuts among three groups of health professionals (dietitians, general practioners, and practice nurses) and the general public in New Zealand (NZ), along with motivators of and deterrents to consuming nuts amongst the general public and their experiences of receiving advice around nut consumption. The NZ electoral roll was used to identify dietitians, general practitioners (GPs), and practice nurses, based on their free-text occupation descriptions, who were then invited to complete a questionnaire with 318, 292, and 149 respondents respectively. 1,600 members of the general public were randomly selected from the roll with 710 respondents. Analyses were performed using chi-squared tests to look at differences in categorical variables and linear regression for differences in other variables between the four survey groups. Although there were significant differences between the four groups regarding the perceptions of nuts, in general there was agreement that nuts are healthy, high in protein and fat, are filling, and some nuts are high in selenium. We noted frequent agreement that the general public participants would consume more if nuts: improved health (67%), were more affordable (60%), or improved the nutrient content (59%) and balance of fats (58%) within their diets. Over half the respondents reported they would eat more nuts if they were advised to do so by a dietitian or doctor, despite less than 4% reporting they had received such advice. The most frequently selected deterrents to increasing nut consumption were: cost (67%), potential weight gain (66%), and leading to eating too much fat (63%). It is concerning that so few among the general public report receiving advice to consume more nuts from health professionals, especially given their apparent responsiveness to such advice. Health professionals could exploit the motivators of nut consumption, while also addressing the deterrents, to promote nut intake. These factors should also be addressed in public health messages to encourage regular nut consumption among the public. Educational initiatives could also be used to improve the nutritional knowledge of GPs and practice nurses with regard to nuts, although even dietitians were unsure of their knowledge in some cases.


Surgical removal of endometriotic lesions alters local and systemic proinflammatory cytokines in endometriosis patients.
To determine the impact of endometriotic lesion removal on local and systemic inflammation. Multiplex cytokine analysis on samples from endometriosis patients before surgery, 2 weeks after surgery, and 3 months after surgery. Academic teaching hospital and university. A total of 43 endometriosis patients before and after excision of lesions by means of laparoscopic surgery, and 25 normal women. None. Plasma, eutopic and ectopic tissue, and peritoneal fluid cytokine levels. Compared with presurgery plasma samples, levels of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL) 2, IL-8, and IL-10 decreased significantly by 2 weeks after surgery in endometriosis patients. Interestingly, levels began to rise at 3 months after surgery in most cases. In tissue, levels of GM-CSF and IL-15 were lower in eutopic tissue, while levels of basic fibroblast growth factor, interferon-inducible protein 10, IL-1 receptor antagonist, granulocyte colony-stimulating factor, macrophage inflammatory protein 1β, IL-7, and IL-5 were higher in eutopic than in ectopic tissue. In peritoneal fluid, levels of IL-5 and IL-12 were higher in early versus advanced stages of endometriosis. Compared with normal women, plasma from endometriosis patients had higher levels of inflammatory cytokines. Endometriotic lesion removal significantly alters the inflammatory profile both locally and systemically in women with endometriosis. Our findings indicate that ectopic lesions are the major drivers of systemic inflammation in endometriosis. The transitory nature of the change may reflect the recurrence of the condition and the influence of systemic factors in its onset.


Sensitivity to biases of case-control studies on medical procedures, particularly surgery and blood transfusion, and risk of Creutzfeldt-Jakob disease.
Evidence of risk of Creutzfeldt-Jakob disease (CJD) associated with medical procedures, including surgery and blood transfusion, is limited by susceptibility to bias in epidemiological studies. Sensitivity to bias was explored using a central-birth-cohort model using data from 18 case-control studies obtained after a review of 494 reports on medical procedures and risk of CJD, systematic for the period January 1, 1989 to December 31, 2011. The validity of the findings in these studies may have been undermined by: recall; control selection; exposure assessment in life-time periods of different duration, out of time-at-risk of effect, or asymmetry in case/control data; and confounding by concomitant blood transfusion at the time of surgery. For sporadic CJD (sCJD), a history of surgery or blood transfusion was associated with risk in some, but not all, recent studies at a ≥10 year lag time, when controls were longitudinally sampled. Space-time aggregation of surgical events was not seen. Surgery at early clinical onset might be overrepresented among cases. Neither surgical history nor blood transfusion unlabelled for donor status, dental treatments or endoscopic examinations were linked to variant CJD (vCJD). These results indicate the need for further research. Common challenges within these studies include access to and content of past medical/dental treatment records for diseases with long incubation periods.


Physiological effects of electroconvulsive therapy and transcranial magnetic stimulation in major depression.
Major depressive episodes are associated with dysregulation of various physiologic systems. Antidepressant medications alter regulation of the hormonal and sleep systems. A thorough understanding of these changes may elucidate the pathophysiologic basis of the disorder [Amsterdam et al., 1989: Psychoneuroendocrinology 14:43-62], and interventions targeted directly at these systems are being increasingly recognized as possible treatments for depression [Wong et al., 2000: Proc Natl Acad Sci USA 97:325-330; Szuba et al., 1996: Proc Am Coll Neuropsychopharmacol Ann Meet]. These physiologic systems are regulated by the major neurotransmitters implicated in the etiology of mood disorders--norepinephrine, serotonin, and dopamine. Many of the hormones of import for this article also act as neurotransmitters and thus alter cerebral activity themselves [Owens and Nemeroff, 1993: Ciba Found Symp 172:296-308; Weitzner, 1998: Psychother Psychosom 67:125-132]. Parenteral infusion of hydrocortisone [DeBattista, 2000: Am J Psychiatry 157:1334-1337] and thyrotropin-releasing hormone (TRH) [Prange et al., 1972: Lancet 2:999-1002; Marangell et al., 1997: Arch Gen Psychiatry 54:214-222; Szuba, 1996: Proc Am Coll Neuropsychopharmacol Ann Meet.] produce acute antidepressant effects. Antagonists to corticotropin-releasing hormone and repeated parenteral infusion of TRH may have antidepressant activity when given during several weeks [Wong, 2000: Proc Natl Acad Sci USA 97:325-330; Arborelius et al., 1999: J Endocrinol 160:1-12; Callahan et al., 1997: Biol Psychiatry 41:264-272]. Manipulations of the sleep system through sleep deprivation can ameliorate depression [Szuba et al., 1994: Psychiatry Res 51:283-295; see Wirz-Justice et al., 1999: Biol Psychiatry 46:445-453 for review]. Sleep deprivation has been shown in more than three dozen studies published in the last three decades to produce marked, acute antidepressant effects in the majority of depressed individuals [Wirz-Justice, et al., 1999: Biol Psychiatry 46:445-453]. Thus, examination of the effects the two nonpharmacologic treatments, electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), produce in these physiologic systems may help elucidate their mechanisms of action, while enhancing understanding of the neurobiology of depressive illness. We will review these physiologic changes associated with depression, the effects that manipulations of these systems can have on depressive disorders, and then describe the effects the two techniques that can stimulate the human brain in vivo, ECT and TMS, exert on these systems.


Transthoracic ultrasonography for the respiratory physician.
Transthoracic ultrasonography is still not utilized to its full potential by respiratory physicians, despite being a well-established and validated imaging modality. It allows for an immediate and mobile assessment that can potentially augment the physical examination of the chest. Ultrasound (US)-assisted procedures can be performed by a single clinician with no sedation and with minimal monitoring, even outside of theatre. The main indications for the use of transthoracic US are: the qualitative and quantitative description of pleural effusions, pleural thickening, diaphragmatic dysfunction and chest-wall and pleural tumours. It may also be used to visualise lung tumours and other parenchymal pulmonary processes provided they abut the pleura. It is at least as sensitive as chest radiographs as far as the detection of a pneumothorax is concerned. It is the ideal tool to assist with thoracocentesis and drainage of effusions. The US-assisted fine-needle aspiration and/or cutting-needle biopsy of extrathoracic lymph nodes, lesions arising from the chest wall, pleura, peripheral lung and mediastinum, are safe and have a high yield in the hands of chest physicians. US may also guide the aspiration and biopsy of diffuse pulmonary infiltrates, consolidations and lung abscesses, provided the chest wall is abutted. Advanced applications of transthoracic US include the diagnosis of pulmonary embolism.


Susceptibility to adverse drug reactions.
The pharmacological effects of a drug depend on its concentration at the site of action, and therefore on the concentration in blood and on the dose. The relationship between the concentration or dose and the corresponding effect can usually be represented mathematically as a rectangular hyperbola; when effect is plotted against log concentration or log dose, the curve is sigmoidal. Inevitably, the effect size and the doses causing benefit and harm will differ among individuals, since they are biological phenomena: some individuals are more likely than others to suffer harm at any given dose. Some harmful effects can occur at much lower doses than those used in therapeutics; that is, the log dose-response curve for harm lies far to the left of the log dose-response curve for benefit. Those who suffer such reactions are hypersusceptible. When the dose-response curves for harm and therapeutic effect are in the same range, dose cannot separate the harmful effects from the therapeutic effects, and adverse reactions are collateral. Toxic effects occur when harmful doses are above the doses needed for benefit. In this review we consider factors that influence a subject's susceptibility to adverse drug reactions. Determinants of susceptibility include Immunological, Genetic, demographic (Age and Sex), Physiological and Exogenous factors (drug-drug interactions, for example), and Diseases and disorders such as renal failure, giving the mnemonic I GASPED. Some susceptibility factors are discrete (for example, all-or-none) and some are continuous; susceptibility can therefore be discrete or continuous; and the factors can interact to determine a person's overall susceptibility to harm.


Validity of spiral analysis in early Parkinson's disease.
Spiral analysis is an objective, easy to administer noninvasive test that has been proposed to measure motor dysfunction in Parkinson disease (PD). We compared overall Unified Parkinson Disease Rating Scale Part III scores to selected indices derived from spiral analysis in seventy-four patients with early PD (mean duration of disease 2.4 +/- 1.7 years, mean age 61.5 +/- 9.7 years). Of the spiral indices, degree of severity, first order zero crossing, second order smoothness, and mean speed were best correlated with total motor Unified Parkinson's Disease Rating Scale (UPDRS) score (all P < 0.01), and these indices showed a gradient across worsening tertiles of UPDRS (P < 0.05). Spiral indices also correlated with UPDRS ratings for the worst side and worst arm scores as well. The domains of bradykinesia, rigidity, and action tremor were correlated with first order crossing, second order smoothness, and mean speed, where as rest tremor was most highly correlated with degree of severity. This suggests that the spiral analysis may supplement motor assessment in PD, although further analysis of spiral metrics, a larger sample and longitudinal data should be evaluated.


Grid-enabled high-throughput in silico screening against influenza A neuraminidase.
Encouraged by the success of the first EGEE biomedical data challenge against malaria (WISDOM), the second data challenge battling avian flu was kicked off in April 2006 to identify new drugs for the potential variants of the influenza A virus. Mobilizing thousands of CPUs on the Grid, the six-week-long high-throughput screening activity has fulfilled over 100 CPU years of computing power and produced around 600 gigabytes of results on the Grid for further biological analysis and testing. In the paper, we demonstrate the impact of a worldwide Grid infrastructure to efficiently deploy large-scale virtual screening to speed up the drug design process. Lessons learned through the data challenge activity are also discussed.


Design and implementation of a web-based patient portal linked to an ambulatory care electronic health record: patient gateway for diabetes collaborative care.
Despite the availability of expert guidelines and widespread diabetes quality improvement efforts, care of patients with diabetes remains suboptimal. Two key barriers to care that may be amenable to informatics-based interventions include (1) lack of patient engagement with therapeutic care plans and (2) lack of medication adjustment by physicians ("clinical inertia") during clinical encounters. The authors describe the conceptual framework, design, implementation, and analysis plan for a diabetes patient web-portal linked directly to the electronic health record (EHR) of a large academic medical center via secure Internet access designed to overcome barriers to effective diabetes care. Partners HealthCare System (Boston, MA), a multi-hospital health care network comprising several thousand physicians caring for over 1 million individual patients, has developed a comprehensive patient web-portal called Patient Gateway that allows patients to interact directly with their EHR via secure Internet access. Using this portal, a specific diabetes interface was designed to maximize patient engagement by importing the patient's current clinical data in an educational format, providing patient-tailored decision support, and enabling the patient to author a "Diabetes Care Plan." The physician view of the patient's Diabetes Care Plan was designed to be concise and to fit into typical EHR clinical workflow. We successfully designed and implemented a Diabetes Patient portal that allows direct interaction with our system's EHR. We are assessing the impact of this advanced informatics tool for collaborative diabetes care in a clinic-randomized controlled trial among 14 primary care practices within our integrated health care system.


Adaptive fractionation therapy: II. Biological effective dose.
Radiation therapy is fractionized to differentiate the cell killing between the tumor and organ at risk (OAR). Conventionally, fractionation is done by dividing the total dose into equal fraction sizes. However, as the relative positions (configurations) between OAR and the tumor vary from fractions to fractions, intuitively, we want to use a larger fraction size when OAR and the tumor are far apart and a smaller fraction size when OAR and the tumor are close to each other. Adaptive fractionation accounts for variations of configurations between OAR and the tumor. In part I of this series, the adaptation minimizes the OAR (physical) dose and maintains the total tumor (physical) dose. In this work, instead, the adaptation is based on the biological effective dose (BED). Unlike the linear programming approach in part I, we build a fraction size lookup table using mathematical induction. The lookup table essentially describes the fraction size as a function of the remaining tumor BED, the OAR/tumor dose ratio and the remaining number of fractions. The lookup table is calculated by maximizing the expected survival of OAR and preserving the tumor cell kill. Immediately before the treatment of each fraction, the OAR-tumor configuration and thus the dose ratio can be obtained from the daily setup image, and then the fraction size can be determined by the lookup table. Extensive simulations demonstrate the effectiveness of our method compared with the conventional fractionation method.


Cutaneous photoprotection from ultraviolet injury by green tea polyphenols.
In animal models, extracts from green tea have been shown to be remarkably effective at reducing the severity of adverse human health effects of overexposure to ultraviolet (UV) radiation. Although sunscreens and other photoprotective measures have traditionally been used for this purpose, there is a need for additional measures and natural products are increasingly being explored for that purpose. Our purpose was to evaluate the effect of polyphenols from green tea on parameters associated with acute UV injury. Areas of skin of normal volunteers were treated with an extract of green tea or one of its constituents. Thirty minutes later, the treated sites were exposed to a 2 minimal erythema dose solar simulated radiation. UV-treated skin was examined clinically for UV-induced erythema, histologically for the presence of sunburn cells or Langerhans cell distributions, or biochemically for UV-induced DNA damage. Application of green tea extracts resulted in a dose-dependent inhibition of the erythema response evoked by UV radiation. The (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) polyphenolic fractions were most efficient at inhibiting erythema, whereas (-)-epigallocatechin (EGC) and (-)-epicatechin (EC) had little effect. On histologic examination, skin treated with green tea extracts reduced the number of sunburn cells and protected epidermal Langerhans cells from UV damage. Green tea extracts also reduced the DNA damage that formed after UV radiation. Polyphenolic extracts of green tea are effective chemopreventive agents for many of the adverse effects of sunlight on human health and may thus serve as natural alternatives for photoprotection.


Expression profiling of palmitate- and oleate-regulated genes provides novel insights into the effects of chronic lipid exposure on pancreatic beta-cell function.
Chronic lipid exposure is implicated in beta-cell dysfunction in type 2 diabetes. We therefore used oligonucleotide arrays to define global alterations in gene expression in MIN6 cells after 48-h pretreatment with oleate or palmitate. Altogether, 126 genes were altered > or =1.9-fold by palmitate, 62 by oleate, and 46 by both lipids. Importantly, nine of the palmitate-regulated genes are known to be correspondingly changed in models of type 2 diabetes. A tendency toward beta-cell de-differentiation was also apparent with palmitate: pyruvate carboxylase and mitochondrial glycerol 3-phosphate dehydrogenase were downregulated, whereas lactate dehydrogenase and fructose 1,6-bisphosphatases were induced. Increases in the latter (also seen with oleate), along with glucosamine-phosphate N-acetyl transferase, imply upregulation of the hexosamine biosynthesis pathway in palmitate-treated cells. However, palmitate also increased expression of calcyclin and 25-kDa synaptosomal-associated protein (SNAP25), which control distal secretory processes. Consistent with these findings, secretory responses to noncarbohydrate stimuli, especially palmitate itself, were upregulated in palmitate-treated cells (much less so with oleate). Indeed, glucose-stimulated secretion was slightly sensitized by chronic palmitate exposure but inhibited by oleate treatment, whereas both lipids enhanced basal secretion. Oleate and palmitate also induced expression of chemokines (MCP-1 and GRO1 oncogene) and genes of the acute phase response (serum amyloid A3). Increases in transcriptional modulators such as ATF3, CCAAT/enhancer binding protein-beta (C/EBPbeta), C/EBPdelta, and c-fos were also seen. The results highlight links between regulated gene expression and phenotypic alterations in palmitate versus oleate-pretreated beta-cells.


Distribution and characteristics of verocytotoxigenic Escherichia coli isolated from Ontario dairy cattle.
Faecal swabs obtained from a random sample of 1131 cows and 659 calves on 100 southern Ontario dairy farms were examined for verocytotoxigenic Escherichia coli (VTEC) using a Vero cell assay. Five isolates from each positive culture were tested similarly. Positive colonies were examined with DNA probes for Shiga-like toxin I (SLT-I) and SLT-II sequences. Probe-negative colonies were tested for neutralization of verocytotoxicity using anti-SLT-I and anti-SLT-IIv antisera. Colonies showing no neutralization response were examined in a polymerase chain reaction procedure. Colonies positive by any test were confirmed to be E. coli biochemically, serotyped, biotyped and tested for antimicrobial resistance. Faecal culture supernatants which were positive in the Vero cell assay, but culture negative, were examined using the neutralization assay. Animals were classified positive by faecal culture supernatant or by positive VTEC isolate. The prevalence rates of VTEC infection in cows and calves were estimated to be 9.5 and 24.7%, respectively. The proportion of animals infected on each farm ranged from 0 to 60% for cows and 0 to 100% for calves. Of 206 VTEC isolates identified, few were of serotypes which have been isolated from humans and none were E. coli O 157.H7.


Characterizing computer-mediated communication, friendship, and social participation in adults with traumatic brain injury.
Adults with traumatic brain injury (TBI) report loss of friendship and reduced social participation after injury, but there is limited information regarding quantity of friends and methods of communication. Our objective was to characterize friendship networks, social participation, and methods of communication, including computer-mediated communication (CMC), used by adults with TBI compared to uninjured adults. Participants were 25 adults with TBI and 26 uninjured healthy comparisons (HC) adults, who completed the Participation Assessment with Recombined Tools-Objective (PART-O) and the Social Network Questionnaire (SNQ). Adults with TBI had significantly fewer total friends and significantly lower levels of productivity and overall social participation. Face-to-face interaction was the preferred method of contact for both groups. Adults with TBI were significantly less likely to use texting as a primary method of communication than their uninjured peers, but used other methods of communication at similar rates. Our study supports prior findings of reduced friendships and reduced social participation after TBI and adds new information about similarities and differences in communication methods between adults with and without TBI.


An ancestral mitochondrial DNA resembling a eubacterial genome in miniature.
Mitochondria, organelles specialized in energy conservation reactions in eukaryotic cells, have evolved from eubacteria-like endosymbionts whose closest known relatives are the rickettsial group of alpha-proteobacteria. Because characterized mitochondrial genomes vary markedly in structure, it has been impossible to infer from them the initial form of the proto-mitochondrial genome. This would require the identification of minimally derived mitochondrial DNAs that better reflect the ancestral state. Here we describe such a primitive mitochondrial genome, in the freshwater protozoon Reclinomonas americana. This protist displays ultrastructural characteristics that ally it with the retortamonads, a protozoan group that lacks mitochondria. R. americana mtDNA (69,034 base pairs) contains the largest collection of genes (97) so far identified in any mtDNA, including genes for 5S ribosomal RNA, the RNA component of RNase P, and at least 18 proteins not previously known to be encoded in mitochondria. Most surprising are four genes specifying a multisubunit, eubacterial-type RNA polymerase. Features of gene content together with eubacterial characteristics of genome organization and expression not found before in mitochondrial genomes indicate that R. americana mtDNA more closely resembles the ancestral proto-mitochondrial genome than any other mtDNA investigated to date.


Relevance of subcortical stroke in dysphagia.
Unilateral cortical lesions are associated with dysphagia in ischemic stroke. It is unclear, however, whether acute subcortical stroke is associated with a similar risk of dysphagia. The aim of this study was to determine the occurrence of dysphagia in purely subcortical stroke and identify dysphagia characteristics. Between 2003 and 2005, videofluoroscopic swallow studies (VFSSs) were completed in 20 consecutive ischemic stroke patients with purely subcortical lesions (right hemisphere damage [RHD]=10, left hemisphere damage [LHD]=10) and 25 age-matched controls. Individuals were classified with dysphagia when at least 2 swallowing measures were 2 standard deviations above mean scores for the control group. Lesion volume, hemisphere, and location were determined from diffusion-weighted magnetic resonance imaging scans. Seven subcortical stroke patients (35%) met VFSS criteria for dysphagia (LHD=5, RHD=2); 4 patients presented with clinically significant dysphagia. A significant interaction between hemisphere and lesion location was identified. Whereas 3 of 5 patients with dysphagia (60%) had lesions to the left periventricular white matter (PVWM), LHD patients without dysphagia did not have PVWM lesions. In contrast, no RHD patients with PVWM lesions had dysphagia, and 6 of 8 patients without dysphagia (75%) had PVWM lesions. Oral transfer was significantly slower in patients with subcortical stroke compared with the healthy adults. Lesions to the left PVWM may be more disruptive to swallowing behavior than similar lesions to the right PVWM. Swallowing deficits involving oral control and transfer may be a marker of subcortical neural axis involvement.


GREETING AND RESPONSE: PREDICTING PARTICIPATION FROM THE CALL OPENING.
Although researchers have used phone surveys for decades, the lack of an accurate picture of the call opening reduces our ability to train interviewers to succeed. Sample members decide about participation quickly. We predict participation using the earliest moments of the call; to do this, we analyze matched pairs of acceptances and declinations from the Wisconsin Longitudinal Study using a case-control design and conditional logistic regression. We focus on components of the first speaking turns: acoustic-prosodic components and interviewer's actions. The sample member's "hello" is external to the causal processes within the call and may carry information about the propensity to respond. As predicted by Pillet-Shore (2012), we find that when the pitch span of the sample member's "hello" is greater the odds of participation are higher, but in contradiction to her prediction, the (less reliably measured) pitch pattern of the greeting does not predict participation. The structure of actions in the interviewer's first turn has a large impact. The large majority of calls in our analysis begin with either an "efficient" or "canonical" turn. In an efficient first turn, the interviewer delays identifying themselves (and thereby suggesting the purpose of the call) until they are sure they are speaking to the sample member, with the resulting efficiency that they introduce themselves only once. In a canonical turn, the interviewer introduces themselves and asks to speak to the sample member, but risks having to introduce themselves twice if the answerer is not the sample member. The odds of participation are substantially and significantly lower for an efficient turn compared to a canonical turn. It appears that how interviewers handle identification in their first turn has consequences for participation; an analysis of actions could facilitate experiments to design first interviewer turns for different target populations, study designs, and calling technologies.