Tamoxifen induces cellular stress in the nervous system by inhibiting cholesterol synthesis.
Tamoxifen (TAM) is an important cancer therapeutic and an experimental tool for effecting genetic recombination using the inducible Cre-Lox technique. Despite its widespread use in the clinic and laboratory, we know little about its effects on the nervous system. This is of significant concern because TAM, via unknown mechanisms, induces cognitive impairment in humans. A hallmark of cellular stress is induction of Activating Transcription Factor 3 (Atf3), and so to determine whether TAM induces cellular stress in the adult nervous system, we generated a knock-in mouse in which Atf3 promoter activity drives transcription of TAM-dependent Cre recombinase (Cre-ERT2); when crossed with tdtomato reporter mice, Atf3 induction results in robust and permanent genetic labeling of cells in which it is up-regulated even transiently. We found that granular neurons of the olfactory bulb and dentate gyrus, vascular cells and ependymal cells throughout the brain, and peripheral sensory neurons expressed tdtomato in response to TAM treatment. We also show that TAM induced Atf3 up-regulation through inhibition of cholesterol epoxide hydrolase (ChEH): reporter expression was mitigated by delivery in vitamin E-rich wheat germ oil (vitamin E depletes ChEH substrates), and was partially mimicked by a ChEH-specific inhibitor. This work demonstrates that TAM stresses cells of the adult central and peripheral nervous systems and highlights concerns about clinical and experimental use of TAM. We propose TAM administration in vitamin E-rich vehicles such as wheat germ oil as a simple remedy.


Rectal injury during robot-assisted radical prostatectomy: incidence and management.
Rectal injury during robot-assisted radical prostatectomy is a rare but significant complication. Since the Clavien grading classification of complications does not include intraoperative injury without further sequelae, rectal injury may be underreported in the literature. We present what is to our knowledge the largest retrospective review to date of rectal injury and subsequent management. We reviewed the records of 6,650 patients who underwent robot-assisted radical prostatectomy at a total of 6 institutions. Patient characteristics, perioperative parameters, pathological findings and rectal injury management were tabulated and analyzed for intraoperative predictors of outcome and subsequent management. A total of 11 rectal injury cases were identified of the 6,650 robot-assisted radical prostatectomies for a combined 0.17% incidence of rectal injury. Of rectal injuries 72.7% were identified intraoperatively and most did well with primary closure. Delayed recognition injury presented as rectourethral fistula without septic complications and required delayed fistula repair after primary diversion. We found no conclusive association of rectal injury with any patient parameter, intraoperative differences, pathological finding or surgeon experience. Posterior prostate plane dissection, including seminal vesicle dissection, is the crucial stage when rectal injury can occur and be identified. Our review of the records at 6 centers revealed a combined 0.17% incidence of rectal injury. This compares favorably to the incidence in modern open and laparoscopic radical prostatectomy series. No preoperative, intraoperative or pathological differences correlated with injury. Cases in which rectal injury was identified intraoperatively required fewer surgical repeat interventions but ultimately each group had acceptable long-term urinary and bowel function results.


Short and long sympathetic-sensory feedback loops in white fat.
We previously demonstrated white adipose tissue (WAT) innervation using the established WAT retrograde sympathetic nervous system (SNS)-specific transneuronal viral tract tracer pseudorabies virus (PRV152) and showed its role in the control of lipolysis. Conversely, we demonstrated WAT sensory innervation using the established anterograde sensory system (SS)-specific transneuronal viral tracer, the H129 strain of herpes simplex virus-1, with sensory nerves showing responsiveness with increases in WAT SNS drive. Several brain areas were part of the SNS outflow to and SS inflow from WAT between these studies suggesting SNS-SS feedback loops. Therefore, we injected both PRV152 and H129 into inguinal WAT (IWAT) of Siberian hamsters. Animals were perfused on days 5 and 6 postinoculation after H129 and PRV152 injections, respectively, and brains, spinal cords, sympathetic, and dorsal root ganglia (DRG) were processed for immunohistochemical detection of each virus across the neuroaxis. The presence of H129+PRV152-colocalized neurons (~50%) in the spinal segments innervating IWAT suggested short SNS-SS loops with significant coinfections (>60%) in discrete brain regions, signifying long SNS-SS loops. Notably, the most highly populated sites with the double-infected neurons were the medial part of medial preoptic nucleus, medial preoptic area, hypothalamic paraventricular nucleus, lateral hypothalamus, periaqueductal gray, oral part of the pontine reticular nucleus, and the nucleus of the solitary tract. Collectively, these results strongly indicate the neuroanatomical reality of the central SNS-SS feedback loops with short loops in the spinal cord and long loops in the brain, both likely involved in the control of lipolysis or other WAT pad-specific functions.


The Yang-Tonifying Herbal Medicine Cynomorium songaricum Extends Lifespan and Delays Aging in Drosophila.
Aging is highly correlated with the progressive loss of physiological function, including cognitive behavior and reproductive capacity, as well as an increased susceptibility to diseases; therefore, slowing age-related degeneration could greatly contribute to human health. Cynomorium songaricum Rupr. (CS) is traditionally used to improve sexual function and treat kidney dysfunction in traditional Chinese medicine, although little is known about whether CS has effects on longevity. Here, we show that CS supplementation in the diet extends both the mean and maximum lifespan of adult female flies. The increase in lifespan with CS was correlated with higher resistance to oxidative stress and starvation and lower lipid hydroperoxides (LPO) levels. Additionally, the lifespan extension was accompanied by beneficial effects, such as improved mating readiness, increased fecundity, and suppression of age-related learning impairment in aged flies. These findings demonstrate the important antiaging effects of CS and indicate the potential applicability of dietary intervention with CS to enhance health and prevent multiple age-related diseases.


Strategic role of the ubiquitin-dependent segregase p97 (VCP or Cdc48) in DNA replication.
Genome amplification (DNA synthesis) is one of the most demanding cellular processes in all proliferative cells. The DNA replication machinery (also known as the replisome) orchestrates genome amplification during S-phase of the cell cycle. Genetic material is particularly vulnerable to various events that can challenge the replisome during its assembly, activation (firing), progression (elongation) and disassembly from chromatin (termination). Any disturbance of the replisome leads to stalling of the DNA replication fork and firing of dormant replication origins, a process known as DNA replication stress. DNA replication stress is considered to be one of the main causes of sporadic cancers and other pathologies related to tissue degeneration and ageing. The mechanisms of replisome assembly and elongation during DNA synthesis are well understood. However, once DNA synthesis is complete, the process of replisome disassembly, and its removal from chromatin, remains unclear. In recent years, a growing body of evidence has alluded to a central role in replisome regulation for the ubiquitin-dependent protein segregase p97, also known as valosin-containing protein (VCP) in metazoans and Cdc48 in lower eukaryotes. By orchestrating the spatiotemporal turnover of the replisome, p97 plays an essential role in DNA replication. In this review, we will summarise our current knowledge about how p97 controls the replisome from replication initiation, to elongation and finally termination. We will also further examine the more recent findings concerning the role of p97 and how mutations in p97 cofactors, also known as adaptors, cause DNA replication stress induced genomic instability that leads to cancer and accelerated ageing. To our knowledge, this is the first comprehensive review concerning the mechanisms involved in the regulation of DNA replication by p97.


Attenuation of wastewater-derived contaminants in an effluent-dominated river.
Although wastewater-derived chemical contaminants undergo transformation through a variety of mechanisms, the relative importance of processes such as biotransformation and photolysis is poorly understood under conditions representative of large rivers. To assess attenuation rates under conditions encountered in such systems, samples from the Trinity River were analyzed for a suite of wastewater-derived contaminants during a period when wastewater effluent accounted for nearly the entire flow of the river over a travel time of approximately 2 weeks. While the concentration of total adsorbable organic iodide, a surrogate for recalcitrant X-ray phase contrast media in wastewater, was approximately constant throughout the river, concentrations of ethylenediamine tetraacetate, gemfibrozil, ibuprofen, metoprolol, and naproxen all decreased between 60% and 90% as the water flowed downstream. Comparison of attenuation rates estimated in the river with rates measured in laboratory-scale microcosms suggests that biotransformation was more important than photolysis for most of the compounds. Further evidence for biotransformation in the river was provided by measurements of the enantiomeric fraction of metoprolol, which showed a gradual decrease as the water moved downstream. Results of this study indicate that natural attenuation can result in significant decreases in concentrations of wastewater-derived contaminants in large rivers.


Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes.
The Cucurbita genus contains several economically important species in the Cucurbitaceae family. Here, we report high-quality genome sequences of C. maxima and C. moschata and provide evidence supporting an allotetraploidization event in Cucurbita. We are able to partition the genome into two homoeologous subgenomes based on different genetic distances to melon, cucumber, and watermelon in the Benincaseae tribe. We estimate that the two diploid progenitors successively diverged from Benincaseae around 31 and 26 million years ago (Mya), respectively, and the allotetraploidization happened at some point between 26 Mya and 3 Mya, the estimated date when C. maxima and C. moschata diverged. The subgenomes have largely maintained the chromosome structures of their diploid progenitors. Such long-term karyotype stability after polyploidization has not been commonly observed in plant polyploids. The two subgenomes have retained similar numbers of genes, and neither subgenome is globally dominant in gene expression. Allele-specific expression analysis in the C. maxima × C. moschata interspecific F1 hybrid and their two parents indicates the predominance of trans-regulatory effects underlying expression divergence of the parents, and detects transgressive gene expression changes in the hybrid correlated with heterosis in important agronomic traits. Our study provides insights into polyploid genome evolution and valuable resources for genetic improvement of cucurbit crops.


Evaluation of a ferret-specific formula for determining body surface area to improve chemotherapeutic dosing.
To use CT-derived measurements to create a ferret-specific formula for body surface area (BSA) to improve chemotherapeutic dosing. 25 adult ferrets (19 live and 6 cadavers). Live subjects were weighed, and body measurements were obtained by each of 3 observers while ferrets were awake and anesthetized. Computed tomography was performed, and a 3-D surface model was constructed with open-source imaging software, from which BSA was estimated. The CT-derived values were compared with BSA calculated on the basis of the traditional tape method for 6 cadavers. To further validate CT analysis software, 11 geometric shapes were scanned and their CT-derived values compared with those calculated directly via geometric formulas. Agreement between methods of surface area estimation was assessed with linear regression. Ferret-specific formulas for BSA were determined with nonlinear regression models. Repeatability among the 3 observers was good for all measurements, but some measurements differed significantly between awake and anesthetized ferrets. Excellent agreement was found between measured versus CT-derived surface area of shapes, traditional tape- versus CT-derived BSA of ferret cadavers, and CT-derived BSA of cadavers with and without monitoring equipment. All surface area formulas performed relatively similarly. CT-derived BSA measurements of ferrets obtained via open-source imaging software were reliable. On the basis of study results, the recommended formula for BSA in ferrets would be 9.94 × (body weight)(2/3); however, this represented a relatively minor difference from the feline-derived formula currently used by most practitioners and would result in little practical change in drug doses.


Effect of melanocyte stimulating hormone on human cultured choroidal melanocytes, uveal melanoma cells, and retinal epithelial cells.
To establish methodology for the culture of human choroidal melanocytes to compare their responsiveness to melanocyte stimulating hormone (MSH) with that of their transformed melanoma counterparts and with that of the retinal epithelial cell. Choroidal melanocytes from the choroid of eyes enucleated for the presence of malignant melanoma were cultured in MCDB 153 medium supplemented with insulin, transferrin, hydrocortisone, glutamine, nystatin, vitamin E, phorbol myristate acetate, bovine hypothalamic extract, cholera toxin, and chelexed fetal calf serum. High yields of pure spindle-shaped bipolar melanocytes were obtained with a doubling time of 3 to 4 days in nine consecutive eyes. Cells continued to divide after 4 months in culture. In contrast, uveal malignant melanoma cells grew rapidly in a relatively simple medium of Ham's F12:DMEM (1:1) supplemented with fetal calf serum, insulin, transferrin and glutamine. This medium was unable to support choroidal melanocytes. Choroidal melanocytes were DOPA-positive with appreciable tyrosinase activity that significantly increased with treatment with MSH. MSH also significantly altered the size, local density, and distribution of primary and mature melanosomes of ocular melanocytes. In contrast, uveal melanoma cells had a low level of tyrosinase activity and failed to respond to MSH with either an increase in enzyme activity or melanosome size. Retinal epithelial cells failed to show significant tyrosinase activity under the conditions studied or any increase in melanosome size in response to MSH. Ocular melanocytes show evidence of regulation by MSH and a range of mitogenic stimuli unlike the transformed melanoma cells, implying a loss of regulatory control in the latter.


Mesoangioblasts suppress T cell proliferation through IDO and PGE-2-dependent pathways.
Human mesoangioblasts are vessel-associated stem cells that are currently in phase I/II clinical trials for the treatment of patients with Duchenne muscular dystrophy. To date, little is known about the effect of mesoangioblasts on human immune cells and vice versa. We hypothesized that mesoangioblasts could modulate the function of immune cells in a similar manner to mesenchymal stromal cells. Human mesoangioblasts did not evoke, but rather potently suppressed human T-cell proliferation and effector function in vitro in a dose- and time-dependent manner. Furthermore, mesoangioblasts exert these inhibitory effects uniformly on human CD4+ and CD8+ T cells in a reversible manner without inducing a state of anergy. Interferon (IFN)-γ and tumor necrosis factor (TNF)-α play crucial roles in the initial activation of mesoangioblasts. Indoleamine 2,3-dioxygenase (IDO) and prostaglandin E-2 (PGE) were identified as key mechanisms of action involved in the mesoangioblast suppression of T-cell proliferation. Together, these data demonstrate a previously unrecognized capacity of mesoangioblasts to modulate immune responses.


Power densities using different cathode catalysts (Pt and CoTMPP) and polymer binders (nafion and PTFE) in single chamber microbial fuel cells.
Cathode catalysts and binders were examined for their effect on power densities in single chamber, air-cathode, microbial fuel cells (MFCs). Chronopotentiometry tests indicated thatthe cathode potential was only slightly reduced (20-40 mV) when Pt loadings were decreased from 2 to 0.1 mg cm(-2), and that Nafion performed better as a Pt binder than poly(tetrafluoroethylene) (PTFE). Replacing the precious-metal Pt catalyst (0.5 mg cm(-2); Nafion binder) with a cobalt material (cobalt tetramethylphenylporphyrin, CoTMPP) produced slightly improved cathode performance above 0.6 mA cm(-2), but reduced performance (<40 mV) at lower current densities. MFC fed batch tests conducted for 35 cycles (31 days) using glucose showed that replacement of the Nafion binder used for the cathode catalyst (0.5 mg of Pt cm(-2)) with PTFE reduced the maximum power densities (from 400 +/- 10 to 480 +/- 20 mW m(-2) to 331 +/- 3 to 360 +/- 10 mW m(-2)). When the Pt loading on cathode was reduced to 0.1 mg cm(-2), the maximum power density of MFC was reduced on average by 19% (379 +/- 5 to 301 +/- 15 mW m(-2); Nafion binder). Power densities with CoTMPP were only 12% (369 +/- 8 mW m(-2)) lower over 25 cycles than those obtained with Pt (0.5 mg cm(-2); Nafion binder). Power densities obtained using with catalysts on the cathodes were approximately 4 times more than those obtained using a plain carbon electrode. These results demonstrate that cathodes used in MFCs can contain very little Pt, and that the Pt can even be replaced with a non-precious metal catalyst such as a CoTMPP with only slightly reduced performance.


Prevalence of sequence variants in the RAS-mitogen activated protein kinase signaling pathway in pre-adolescent children with hypertrophic cardiomyopathy.
Most cases of apparently idiopathic hypertrophic cardiomyopathy (HCM) in children are caused by mutations in cardiac sarcomere protein genes. HCM also commonly occurs as an associated feature in some patients with disorders caused by mutations in genes encoding components of the RAS-mitogen activated protein kinase (MAPK) signaling pathway. Although diagnosis of these disorders is based on typical phenotypic features, the dysmorphic manifestations can be subtle and therefore overlooked. The aim of this study was to determine the prevalence of mutations in RAS-MAPK genes in preadolescent children with idiopathic HCM. Seventy-eight patients diagnosed with apparently nonsyndromic HCM aged ≤13 years underwent clinical and genetic evaluation. The entire protein coding sequence of 9 genes implicated in Noonan syndrome and related conditions (PTPN11, SOS1, HRAS, KRAS, NRAS, BRAF, RAF1, MAP2K1, and MAP2K2), together with CBL (exons 8 and 9) and SHOC2 (4A>G), were screened for mutations. Five probands (6.4%) carried novel sequence variants in SOS1 (2 individuals), BRAF, MAP2K1, and MAP2K2. Structural and molecular data suggest that these variants may have functional significance. Nine cardiac sarcomere protein genes were screened also; 2 individuals also had mutations in MYBPC. This study reports novel and potentially pathogenic sequence variants in genes of the RAS-MAPK pathway, suggesting that genetic lesions promoting signaling dysregulation through RAS contribute to disease pathogenesis or progression in children with HCM.


The influence of Masters education on the professional lives of British and German nurses and the further professionalization of nursing.
This article reports on findings from a qualitative study which explored the influence of a Masters in Nursing on the professional lives of British and German nurses and its role in further professionalizing nursing. A collaborative Masters programme was delivered in the United Kingdom and Germany. This provided an opportunity to study the influence of the programme on the professionalization of nursing in different country contexts. Continuing education is thought to contribute to furthering professionalization. Evidence to support this in the field of nursing is limited. An interpretive research design was used and data were collected via semi-structured interviews with ten German nurses and nine British nurses. Data were collected in the United Kingdom and Germany from August 2006 to February 2007. Interviews were recorded and transcribed, and data were analysed using a template approach with further immersion and crystalization of the data. Nurses' personal and professional confidence improved; research-based evidence was used to underpin changes made to practice; new roles and careers emerged; multi-professional working was enhanced; and nurses rediscovered nursing and championed the profession. A diagram is presented based on the findings. Masters education is at the centre as the catalyst with four interconnecting circles, which depict elements that contribute to professionalization. The diagram highlights overlap and interplay between nurses' increased personal confidence, improved cognitive functioning, evidence-based practice development and enhanced professionalism. Findings support the theory that this Masters in Nursing programme enhanced practice and further professionalization of nursing in both countries.


Microcalorimetry and fluorescence show stable peptide nucleic acid (PNA) duplexes in high organic content solvent mixtures.
The selectivity of nucleic acid hybridisation can be exploited to template chemical reactions, enabling materials discovery by chemical evolution. However, to date the range of reactions that can be used has been limited to those that are compatible with aqueous media, since the addition of organic co-solvents can have a large impact on the stability of nucleic acid duplexes. Peptide nucleic acids (PNAs) are promising in this regard because previous studies have suggested they may be stable as duplexes in high organic content solvent mixtures. Here, we use micro-differential scanning calorimetry (micro-DSC) to confirm for the first time that double-stranded PNA (dsPNA) is stable in N,N-dimethylformamide (DMF)/water mixtures up to 95 vol% DMF. Using fluorescence, we corroborate these results and show that the isothermal annealing of PNA in high DMF content solution is also rapid. These findings suggest that PNA could enable the use of a range of water-sensitive chemistries in nucleic acid templating applications.


Theoretical study of the ground and excited states of 7-methyl guanine and 9-methyl guanine: comparison with experiment.
The keto-enol tautomerization of 7-methyl-guanine and 9-methyl-guanine in the excited state was investigated using the time-dependent DFT (TDDFT) method. For both species, the potential energy surfaces of the ground state and two lowest singlet excited states (due to pi-->pi* and n-->pi* transitions) have been investigated and their features discussed in terms of consequences on the excited state dynamics. The findings suggest that, for both species, the state due to the n-->pi* transition, suspected to be an intermediate in the excited state deactivation, exhibits two minima with the second minimum characterized by an elongated N1-H distance. This structure, intermediate between enol and keto tautomers, might play a role in the excited state relaxation. The existence of this second well, however, is observed in both 7- and 9-methyl-guanine, which suggests that it cannot account alone for the different photophysical behavior of these species.


Full on-chip nanoliter immunoassay by geometrical magnetic trapping of nanoparticle chains.
We propose an original concept to perform a complete on-chip sandwich immunoassay on magnetic nanoparticles that are self-assembled in chains in a uniform magnetic field. The magnetic chains are retained over periodically enlarged cross sections of a microfluidic channel. Thereby they strongly interact with the flow and rapidly capture the total of a low number of target molecules from nanoliter sample volumes. As an example, we demonstrate the detection of murine monoclonal antibodies in a noncompetitive sandwich immunoassay with a detection limit of 1 ng mL(-1) in nanoliters of hybridoma cell culture medium.


The tyrosine kinase Lyn limits the cytokine responsiveness of plasma cells to restrict their accumulation in mice.
Maintenance of an appropriate number of plasma cells, long-lived antibody-producing cells that are derived from B cells, is essential for maintaining immunological memory while limiting disease. Plasma cell survival relies on extrinsic factors, the limited availability of which determines the size of the plasma cell population. Mice deficient in the nonreceptor tyrosine kinase Lyn are prone to an autoimmune disease that is characterized by inflammation and an excess of plasma cells (plasmacytosis). We demonstrated that the plasmacytosis was intrinsic to B cells and independent of inflammation. We also showed that Lyn attenuated signaling by signal transducer and activator of transcription 3 (STAT3) and STAT5 in response to the cytokines interleukin-6 (IL-6) and IL-3, respectively, in two previously uncharacterized plasma cell signaling pathways. Thus, in the absence of Lyn, the survival of plasma cells was improved, which enabled the plasma cells to become established in excess numbers in niches in vivo. These data identify Lyn as a key regulator of survival signaling in plasma cells, limiting plasma cell accumulation and autoimmune disease susceptibility.


A Multi-Area Stochastic Model for a Covert Visual Search Task.
Decisions typically comprise several elements. For example, attention must be directed towards specific objects, their identities recognized, and a choice made among alternatives. Pairs of competing accumulators and drift-diffusion processes provide good models of evidence integration in two-alternative perceptual choices, but more complex tasks requiring the coordination of attention and decision making involve multistage processing and multiple brain areas. Here we consider a task in which a target is located among distractors and its identity reported by lever release. The data comprise reaction times, accuracies, and single unit recordings from two monkeys' lateral interparietal area (LIP) neurons. LIP firing rates distinguish between targets and distractors, exhibit stimulus set size effects, and show response-hemifield congruence effects. These data motivate our model, which uses coupled sets of leaky competing accumulators to represent processes hypothesized to occur in feature-selective areas and limb motor and pre-motor areas, together with the visual selection process occurring in LIP. Model simulations capture the electrophysiological and behavioral data, and fitted parameters suggest that different connection weights between LIP and the other cortical areas may account for the observed behavioral differences between the animals.


Structure-activity analysis of quorum-sensing signaling peptides from Streptococcus mutans.
Streptococcus mutans secretes and utilizes a 21-amino-acid signaling peptide pheromone to initiate quorum sensing for genetic competence, biofilm formation, stress responses, and bacteriocin production. In this study, we designed and synthesized a series of truncated peptides and peptides with amino acid substitutions to investigate their structure-activity relationships based on the three-dimensional structures of S. mutans wild-type signaling peptide UA159sp and C-terminally truncated peptide TPC3 from mutant JH1005 defective in genetic competence. By analyzing these peptides, we demonstrated that the signaling peptide of S. mutans has at least two functional domains. The C-terminal structural motif consisting of a sequence of polar hydrophobic charged residues is crucial for activation of the signal transduction pathway, while the core alpha-helical structure extending from residue 5 to the end of the peptide is required for receptor binding. Peptides in which three or more residues were deleted from the C terminus did not induce genetic competence but competitively inhibited quorum sensing activated by UA159sp. Disruption of the amphipathic alpha-helix by replacing the Phe-7, Phe-11, or Phe-15 residue with a hydrophilic residue resulted in a significant reduction in or complete loss of the activity of the peptide. In contrast to the C-terminally truncated peptides, these peptides with amino acid substitutions did not compete with UA159sp to activate quorum sensing, suggesting that disruption of the hydrophobic face of the alpha-helical structure results in a peptide that is not able to bind to the receptor. This study is the first study to recognize the importance of the signaling peptide C-terminal residues in streptococcal quorum sensing.


Flustered and faithful: embarrassment as a signal of prosociality.
Although individuals experience embarrassment as an unpleasant, negative emotion, the authors argue that expressions of embarrassment serve vital social functions, signaling the embarrassed individual's prosociality and fostering trust. Extending past research on embarrassment as a nonverbal apology and appeasement gesture, the authors demonstrate that observers recognize the expression of embarrassment as a signal of prosociality and commitment to social relationships. In turn, observers respond with affiliative behaviors toward the signaler, including greater trust and desire to affiliate with the embarrassed individual. Five studies tested these hypotheses and ruled out alternative explanations. Study 1 demonstrated that individuals who are more embarrassable also reported greater prosociality and behaved more generously than their less embarrassable counterparts. Results of Studies 2-5 revealed that observers rated embarrassed targets as being more prosocial and less antisocial relative to targets who displayed either a different emotion or no emotion. In addition, observers were more willing to give resources and express a desire to affiliate with these targets, and these effects were mediated by perceptions of the targets as prosocial.


Regulation of beta -catenin transformation by the p300 transcriptional coactivator.
The beta-catenin protein plays a critical role in embryonic development and mature tissue homeostasis through its effects on E-cadherin-mediated cell adhesion and Wnt-dependent signal transduction. In colon and other cancers, mutations of beta-catenin or the adenomatous polyposis coli (APC) tumor suppressor appear to stabilize beta-catenin and enhance its interaction with T cell factor (TCF) or lymphoid enhancer factor (Lef) transcription factors. At present, a complete picture of the means by which beta-catenin's interactions with TCF/Lef proteins contribute to neoplastic transformation is lacking. We report that the transcriptional coactivator p300 interacts with beta-catenin in vitro and in vivo and is critical for beta-catenin-mediated neoplastic transformation. p300 synergistically activates beta-catenin/TCF transcription, and their biochemical association requires the CH1 domain of p300 and a region of beta-catenin that includes its NH(2)-terminal transactivation domain and the first two armadillo repeats. Lowering of cellular p300 levels by using a ribozyme directed against p300 reduced TCF transcriptional activity and inhibited the neoplastic growth properties of a beta-catenin-transformed rat epithelial cell line and a human colon carcinoma line with a beta-catenin mutation. These findings demonstrate a critical role for p300 in beta-catenin/TCF transcription and in cancers arising from defects in beta-catenin regulation.


Multilabel learning via random label selection for protein subcellular multilocations prediction.
Prediction of protein subcellular localization is an important but challenging problem, particularly when proteins may simultaneously exist at, or move between, two or more different subcellular location sites. Most of the existing protein subcellular localization methods are only used to deal with the single-location proteins. In the past few years, only a few methods have been proposed to tackle proteins with multiple locations. However, they only adopt a simple strategy, that is, transforming the multilocation proteins to multiple proteins with single location, which does not take correlations among different subcellular locations into account. In this paper, a novel method named random label selection (RALS) (multilabel learning via RALS), which extends the simple binary relevance (BR) method, is proposed to learn from multilocation proteins in an effective and efficient way. RALS does not explicitly find the correlations among labels, but rather implicitly attempts to learn the label correlations from data by augmenting original feature space with randomly selected labels as its additional input features. Through the fivefold cross-validation test on a benchmark data set, we demonstrate our proposed method with consideration of label correlations obviously outperforms the baseline BR method without consideration of label correlations, indicating correlations among different subcellular locations really exist and contribute to improvement of prediction performance. Experimental results on two benchmark data sets also show that our proposed methods achieve significantly higher performance than some other state-of-the-art methods in predicting subcellular multilocations of proteins. The prediction web server is available at >http://levis.tongji.edu.cn:8080/bioinfo/MLPred-Euk/ for the public usage.


Haplosporidiosis in the Pacific oyster Crassostrea gigas from the French Atlantic coast.
Two cases of haplosporidian infection occurred during 1993 in Pacific oysters Crassostrea gigas from the French Atlantic coast. The localization and ultrastructure of the plasmodia are described. In situ hybridization of infected tissue sections was conducted with DNA probes for oyster-infecting haplosporidians. The Haplosporidium nelsoni-specific DNA probe MSX1347 hybridized with the C. gigas parasite, and the H. costale-specific probe SSO1318 did not hybridize. Total genomic DNA was extracted from the infected tissue sections for polymerase chain reaction (PCR) amplification of the haplosporidian. PCR amplifications with H. nelsoni-specific primers and with 'universal' actin primers did not yield the expected products of 573 and 700 bp, respectively. A series of primers was designed to amplify short regions of small subunit ribosomal DNA (SSU rDNA) from most haplosporidians. The primers encompass a highly variable region of the SSU rDNA and did not amplify oyster DNA. PCR amplification of the infected C. gigas genomic DNA with these primers yielded the expected-sized product from the primer pair targeting the shortest region (94 bp). This PCR product was sequenced and it was identical to the corresponding SSU rDNA region of H. nelsoni.


Total laparoscopic hysterectomy for early stage endometrial cancer in obese and morbidly obese women.
This is a retrospective observational study, where we have evaluated the role of total laparoscopic hysterectomy (TLH) in obese and morbidly obese patients with early stage endometrial cancer. Our study illustrates that low conversion rates are achievable when appropriately trained surgeons undertake this procedure. All the women with high BMI were operated on laparoscopically in preference to laparotomy, unless there was an obvious contraindication such as a very large uterus or disseminated disease. We have also shown low conversation and complication rates for our patients, in particular a low rate of wound infection. This is in contrast to the high rate of wound infection and prolonged hospital stay reported for obese patients in the literature. Our study shows that TLH for endometrial cancer in obese women is feasible, safe and is likely to be cost-effective and adds to the weight of evidence for its use in this condition.


Who receives home-based perinatal palliative care: experience from Poland.
The current literature suggests that perinatal palliative care (PPC) programs should be comprehensive, initiated early, and integrative. So far there have been very few publications on the subject of home-based PC of newborns and neonates. Most publications focus on hospital-based care, mainly in the neonatal intensive care units. To describe the neonates and infants who received home-based palliative care in Lodz Region between 2005 and 2011. A retrospective review of medical records. 53 neonates and infants were admitted to a home hospice in Lodz Region between 2005 and 2011. In general, they are a growing group of patients referred to palliative care. Congenital diseases (41%) were the primary diagnoses; out of 53 patients 16 died, 20 were discharged home, and 17 stayed under hospice care until 2011. The most common cause of death (56%) was cardiac insufficiency. Neurological symptoms (72%) and dysphagia (58%) were the most common clinical problems. The majority of children (45%) had a feeding tube inserted and were oxygen dependent (45%); 39 families received psychological care and 31 social supports. For terminally ill neonates and infants, perinatal palliative care is an option which improves the quality of their lives and provides the family with an opportunity to say goodbye.


NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial).
Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer. Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy). The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice. ISRCTN45750457.


Olfactory perception of oviposition-deterring fatty acids and their methyl esters by the Asian corn borer, Ostrinia furnacalis.
Olfactory perception of myristic, palmitic, stearic and oleic acids and their corresponding methyl esters by Asian corn borer moths, Ostrinia furnacalis (Guenée) (Lepidoptera: Crambidae) was investigated. It was found that mated females with both antennae amputated, in contrast to intact females and females with one antenna removed, could not discriminate between simultaneously provided control filter papers and filters treated with a blend of oviposition-deterring fatty acids. Oviposition by mated females exhibited a very marked periodicity, with all egg masses deposited during the scotophase and most egg masses laid before midnight. According to the peak and trough period of oviposition, electroantennogram (EAG) responses from both mated females and males to the four fatty acids and four methyl esters were tested within two two-hour periods from 3 to 5 hours after the start of darkness and from 1 to 3 hours after light onset, respectively. Significant EAG responses above solvent and background were elicited by all test chemicals from females, and by most of the test compounds from males. EAG values of all test chemicals from mated females were not statistically different between the two test periods except for methyl myristate. Conversely, EAG responses from mated males to myristic acid, stearic acid and their methyl esters significantly differed between the two test periods.


Gray matter volume reduction in the chronic fatigue syndrome.
The chronic fatigue syndrome (CFS) is a disabling disorder of unknown etiology. The symptomatology of CFS (central fatigue, impaired concentration, attention and memory) suggests that this disorder could be related to alterations at the level of the central nervous system. In this study, we have used an automated and unbiased morphometric technique to test whether CFS patients display structural cerebral abnormalities. We mapped structural cerebral morphology and volume in two cohorts of CFS patients (in total 28 patients) and healthy controls (in total 28 controls) from high-resolution structural magnetic resonance images, using voxel-based morphometry. Additionally, we recorded physical activity levels to explore the relation between severity of CFS symptoms and cerebral abnormalities. We observed significant reductions in global gray matter volume in both cohorts of CFS patients, as compared to matched control participants. Moreover, the decline in gray matter volume was linked to the reduction in physical activity, a core aspect of CFS. These findings suggest that the central nervous system plays a key role in the pathophysiology of CFS and point to a new objective and quantitative tool for clinical diagnosis of this disabling disorder.


A new mouse model to explore therapies for preeclampsia.
Pre-eclampsia, a pregnancy-specific multisystemic disorder is a leading cause of maternal and perinatal mortality and morbidity. This syndrome has been known to medical science since ancient times. However, despite considerable research, the cause/s of preeclampsia remain unclear, and there is no effective treatment. Development of an animal model that recapitulates this complex pregnancy-related disorder may help to expand our understanding and may hold great potential for the design and implementation of effective treatment. Here we show that the CBA/J x DBA/2 mouse model of recurrent miscarriage is also a model of immunologically-mediated preeclampsia (PE). DBA/J mated CBA/J females spontaneously develop many features of human PE (primigravidity, albuminuria, endotheliosis, increased sensitivity to angiotensin II and increased plasma leptin levels) that correlates with bad pregnancy outcomes. We previously reported that antagonism of vascular endothelial growth factor (VEGF) signaling by soluble VEGF receptor 1 (sFlt-1) is involved in placental and fetal injury in CBA/J x DBA/2 mice. Using this animal model that recapitulates many of the features of preeclampsia in women, we found that pravastatin restores angiogenic balance, ameliorates glomerular injury, diminishes hypersensitivity to angiotensin II and protects pregnancies. We described a new mouse model of PE, were the relevant key features of human preeclampsia develop spontaneously. The CBA/J x DBA/2 model, that recapitulates this complex disorder, helped us identify pravastatin as a candidate therapy to prevent preeclampsia and its related complications. We recognize that these studies were conducted in mice and that clinical trials are needed to confirm its application to humans.


Jet and ultrasonic nebuliser output: use of a new method for direct measurement of aerosol output.
Output from jet nebulisers is calibrated traditionally by weighing them before and after nebulisation, but the assumption that the weight difference is a close measure of aerosol generation could be invalidated by the concomitant process of evaporation. A method has been developed for measuring aerosol output directly by using a solute (fluoride) tracer and aerosol impaction, and this has been compared with the traditional weight loss method for two Wright, six Turbo, and four Micro-Cirrus jet nebulisers and two Microinhaler ultrasonic nebulisers. The weight loss method overestimated true aerosol output for all jet nebulisers. The mean aerosol content, expressed as a percentage of the total weight loss, varied from as little as 15% for the Wright jet nebulisers to 54% (range 45-61%) for the Turbo and Micro-Cirrus jet nebulisers under the operating conditions used. In contrast, there was no discrepancy between weight loss and aerosol output for the ultrasonic nebulisers. These findings, along with evidence of both concentrating and cooling effects from jet nebulisation, confirm that total output from jet nebulisers contains two distinct fractions, vapour and aerosol. The vapour fraction, but not the aerosol fraction, was greatly influenced by reservoir temperature within the nebuliser; so the ratio of aerosol output to total weight loss varied considerably with temperature. It is concluded that weight loss is an inappropriate method of calibrating jet nebuliser aerosol output, and that this should be measured directly.


Liver sampling: a vital window into HBV pathogenesis on the path to functional cure.
In order to optimally refine the multiple emerging drug targets for hepatitis B virus (HBV), it is vital to evaluate virological and immunological changes at the site of infection. Traditionally liver biopsy has been the mainstay of HBV disease assessment, but with the emergence of non-invasive markers of liver fibrosis, there has been a move away from tissue sampling. Here we argue that liver biopsy remains an important tool, not only for the clinical assessment of HBV but also for research progress and evaluation of novel agents. The importance of liver sampling has been underscored by recent findings of specialised subsets of tissue-resident immune subsets capable of efficient pathogen surveillance, compartmentalised in the liver and not sampled in the blood. Importantly, the assessment of virological parameters, such as cccDNA quantitation, also requires access to liver tissue. We discuss strategies to maximise information obtained from the site of infection and disease pathology. Fine needle aspirates of the liver may allow longitudinal sampling of the local virus/host landscape. The careful utilisation of liver tissue and aspirates in conjunction with blood will provide critical information in the assessment of new therapeutics for the functional cure of HBV.


Risk prediction of emergency department revisit 30 days post discharge: a prospective study.
Among patients who are discharged from the Emergency Department (ED), about 3% return within 30 days. Revisits can be related to the nature of the disease, medical errors, and/or inadequate diagnoses and treatment during their initial ED visit. Identification of high-risk patient population can help device new strategies for improved ED care with reduced ED utilization. A decision tree based model with discriminant Electronic Medical Record (EMR) features was developed and validated, estimating patient ED 30 day revisit risk. A retrospective cohort of 293,461 ED encounters from HealthInfoNet (HIN), Maine's Health Information Exchange (HIE), between January 1, 2012 and December 31, 2012, was assembled with the associated patients' demographic information and one-year clinical histories before the discharge date as the inputs. To validate, a prospective cohort of 193,886 encounters between January 1, 2013 and June 30, 2013 was constructed. The c-statistics for the retrospective and prospective predictions were 0.710 and 0.704 respectively. Clinical resource utilization, including ED use, was analyzed as a function of the ED risk score. Cluster analysis of high-risk patients identified discrete sub-populations with distinctive demographic, clinical and resource utilization patterns. Our ED 30-day revisit model was prospectively validated on the Maine State HIN secure statewide data system. Future integration of our ED predictive analytics into the ED care work flow may lead to increased opportunities for targeted care intervention to reduce ED resource burden and overall healthcare expense, and improve outcomes.


Accommodating uncertainty in comparative risk.
Comparative risk projects can provide broad policy guidance but they rarely have adequate scientific foundations to support precise risk rankings. Many extant projects report rankings anyway, with limited attention to uncertainty. Stochastic uncertainty, structural uncertainty, and ignorance are types of incertitude that afflict risk comparisons. The recently completed New Jersey Comparative Risk Project was innovative in trying to acknowledge and accommodate some historically ignored uncertainties in a substantive manner. This article examines the methods used and lessons learned from the New Jersey project. Monte Carlo techniques were used to characterize stochastic uncertainty, and sensitivity analysis helped to manage structural uncertainty. A deliberative process and a sorting technique helped manage ignorance. Key findings are that stochastic rankings can be calculated but they reveal such an alarming degree of imprecision that the rankings are no longer useful, whereas sorting techniques are helpful in spite of uncertainty. A deliberative process is helpful to counter analytical overreaching.


DALYs, dollars and dogs: how best to analyse the economics of controlling zoonoses.
Decision-makers increasingly require comprehensive economic metrics summarising and comparing the benefits and costs of controlling zoonotic diseases. The impact of disease in people is conventionally quantified in non-monetary terms, usually a disability-adjusted life year (DALY), whereas the losses due to disease in animals, particularly livestock, are quantified in monetary terms. The potential for the development of a non-monetary metric for ill health in animals, based on life years lost and disability, is discussed and rejected. Within and across animal species and livestock production systems, maximising life spans is not a consistent goal and morbidity/disabilities have very different weights and often lead to culling. By relating livestock losses to a measure of national income forgone, the recently developed alternative of converting monetary losses due to livestock illness into an animal loss equivalent (ALE) provides a viable solution. Based on this, the literature on the economics of controlling zoonoses is revisited and four options for quantifying and comparing benefits and costs are examined and illustrated using numerical examples. These are i) the simplistic grouping of all monetary elements and their comparison to DALYs averted (described as the aggregate net cost method), ii) the separable costs method, iii) the use of ALEs to convert all benefits to a non-monetary equivalent, termed the zoonotic DALY (zDALY), or iv) the use of a full monetary cost-benefit analysis, based on converting DALYs to a monetary equivalent. The strengths and weaknesses of each are discussed. For effective prioritisation and decision-making, it is vital that an analytical approach is widely adopted which yields consistent results and which supports the control of zoonoses.


Prostate-specific antigen (PSA) protein does not affect growth of prostate cancer cells in vitro or prostate cancer xenografts in vivo.
Prostate-specific antigen (PSA) is produced in high amounts by normal and malignant prostate cancer cells. PSA is a serine protease with substrates that include semenogelin I and II, insulin-like growth factor binding protein 3, fibronectin, and laminin. PSA, via its enzymatic activity, may play a role in growth, invasion, and metastasis of prostate cancer cells. Recent data also suggest that the PSA protein itself, independent of enzymatic activity, may also function as an endothelial cell-specific inhibitor of angiogenesis. Human (PC3, DU145) and rat (AT2, AT6) prostate cancer cell lines were transfected with the full PSA gene encoding preproPSA protein. PSA-producing clones of each cell line were selected and the amount of enzymatically active PSA produced by each cell line determined using a PSA-specific fluorescent peptide substrate. In vitro and in vivo growth characteristics of PSA-producing transfectants were compared to neomycin controls and wild type cells. All selected clones produced and secreted PSA (5-120 ng/ml/10(5) cells). None of the PSA-transfected cell lines produced detectable amounts of enzymatically active PSA. Production of enzymatically inactive PSA by prostate cancer cell lines did not alter growth kinetics in vitro. PSA-producing xenograft doubling times in vivo were similar to neomycin controls and wild type. Although recent reports suggest the PSA protein itself may be antiangiogenic, our results demonstrate that production of PSA protein by prostate cancer cells does not significantly alter growth in vitro or in vivo.


Cloning and characterization of a new armadillo family member, p0071, associated with the junctional plaque: evidence for a subfamily of closely related proteins.
Cell contacts of the adherens type are organized around transmembrane proteins of the cadherin family. Whereas the extracellular domains mediate homophilic interactions between cadherins of neighbouring cells the cytoplasmic domains organize a set of proteins into the junctional plaque. Among these junctional plaque proteins are members of the armadillo gene family, beta-catenin, plakoglobin (gamma-catenin), B6P/plakophilin and p120. These proteins are assumed to play a key role in cell cell signalling through intercellular junctions. Here we report cloning of a cDNA encoding a new armadillo family member, p0071, closely related to p120 and B6P/plakophilin and more distantly related to armadillo, plakoglobin, beta-catenin and other members of the gene family. The deduced amino acid sequence encodes a basic protein of 1,211 amino acids with a central armadillo repeat region which is conserved in sequence and organization of its ten individual motifs between p120, B6P/plakophilin and p0071. In contrast the end domains of the three proteins are variable in size and sequence. The RNA coding for p0071 is expressed in all tissues examined. Using antibodies generated against the armadillo repeat region of the protein we show that p0071 is localized at cell-cell borders and is expressed in the desmosomal plaque of some cultured epithelial cells. The protein seems to be an accessory component of the desmosomal plaque as well as of other adhesion plaques and might be involved in regulating junctional plaque organization and cadherin function. Our data provide evidence for a subfamily of armadillo related proteins that share not only structural features but also have in common their localisation in the junctional plaque. We therefore suggest that family members exert similar functions and might be involved in cell signalling through cell contacts.


A closed-form solution of the bit-error rate for optical wireless communication systems over atmospheric turbulence channels.
Atmospheric turbulence is a major limiting factor in an optical wireless communication (OWC) link. The turbulence distorts the phase of the propagating optical fields and limits the focusing capabilities of the telescope antennas. Hence, a detector array is required to capture the widespread signal energy in the focal-plane. This paper addresses the bit-error rate (BER) performance of optical wireless communication (OWC) systems employing a detector array in the presence of turbulence. Here, considering the gamma-gamma turbulence model, we propose a blind estimation scheme that provides the closed-form expression of the BER by exploiting the information of the data output of each pixel, which is based on the singular value decomposition of the sample matrix of the received signals after the code-matched filter. Instead of assuming spatially white additive noise, we consider the case where the noise spatial covariance matrix is unknown. The new method can be applied to either the single transmitter or the multi-transmitter cases. Simulation results for different Rytov variances are presented, which conform closely to the results of the proposed model.


Worms, bacteria, and micronutrients: an elegant model of our diet.
Micronutrients are required in small proportions in a diet to carry out key metabolic roles for biomass and energy production. Humans receive micronutrients either directly from their diet or from gut microbiota that metabolize other nutrients. The nematode Caenorhabditis elegans and its bacterial diet provide a relatively simple and genetically tractable model to study both direct and microbe-mediated effects of micronutrients. Recently, this model has been used to gain insight into the relationship between micronutrients, physiology, and metabolism. In particular, two B-type vitamins, vitamin B12 and folate, have been studied in detail. Here we review how C. elegans and its bacterial diet provide a powerful interspecies systems biology model that facilitates the precise delineation of micronutrient effects and the mechanisms involved.


Multifaceted intervention to improve medication adherence and secondary prevention measures after acute coronary syndrome hospital discharge: a randomized clinical trial.
Adherence to cardioprotective medication regimens in the year after hospitalization for acute coronary syndrome (ACS) is poor. To test a multifaceted intervention to improve adherence to cardiac medications. In this randomized clinical trial, 253 patients from 4 Department of Veterans Affairs medical centers located in Denver (Colorado), Seattle (Washington); Durham (North Carolina), and Little Rock (Arkansas) admitted with ACS were randomized to the multifaceted intervention (INT) or usual care (UC) prior to discharge. The INT lasted for 1 year following discharge and comprised (1) pharmacist-led medication reconciliation and tailoring; (2) patient education; (3) collaborative care between pharmacist and a patient's primary care clinician and/or cardiologist; and (4) 2 types of voice messaging (educational and medication refill reminder calls). The primary outcome of interest was proportion of patients adherent to medication regimens based on a mean proportion of days covered (PDC) greater than 0.80 in the year after hospital discharge using pharmacy refill data for 4 cardioprotective medications (clopidogrel, β-blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors [statins], and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers [ACEI/ARB]). Secondary outcomes included achievement of blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level targets. RESULTS Of 253 patients, 241 (95.3%) completed the study (122 in INT and 119 in UC). In the INT group, 89.3% of patients were adherent compared with 73.9% in the UC group (P = .003). Mean PDC was higher in the INT group (0.94 vs 0.87; P< .001). A greater proportion of intervention patients were adherent to clopidogrel (86.8% vs 70.7%; P = .03), statins (93.2% vs 71.3%; P < .001), and ACEI/ARB (93.1% vs 81.7%; P = .03) but not β-blockers (88.1% vs 84.8%; P = .59). There were no statistically significant differences in the proportion of patients who achieved BP and LDL-C level goals. A multifaceted intervention comprising pharmacist-led medication reconciliation and tailoring, patient education, collaborative care between pharmacist and patients' primary care clinician and/or cardiologist, and voice messaging increased adherence to medication regimens in the year after ACS hospital discharge without improving BP and LDL-C levels. Understanding the impact of such improvement in adherence on clinical outcomes is needed prior to broader dissemination of the program. clinicaltrials.gov Identifier: NCT00903032.


International Society for Sexual Medicine's guidelines for the diagnosis and treatment of premature ejaculation.
Over the past 20 years our knowledge of premature ejaculation (PE) has significantly advanced. Specifically, we have witnessed substantial progress in understanding the physiology of ejaculation, clarifying the real prevalence of PE in population-based studies, reconceptualizing the definition and diagnostic criterion of the disorder, assessing the psychosocial impact on patients and partners, designing validated diagnostic and outcome measures, proposing new pharmacologic strategies and examining the efficacy, safety and satisfaction of these new and established therapies. Given the abundance of high level research it seemed like an opportune time for the International Society for Sexual Medicine (ISSM) to promulgate an evidenced-based, comprehensive and practical set of clinical guidelines for the diagnosis and treatment of PE. Develop clearly worded, practical, evidenced-based recommendations for the diagnosis and treatment of PE for family practice clinicians as well as sexual medicine experts. Method. Review of the literature. This article contains the report of the ISSM PE Guidelines Committee. It affirms the ISSM definition of PE and suggests that the prevalence is considerably lower than previously thought. Evidence-based data regarding biological and psychological etiology of PE are presented, as is population-based statistics on normal ejaculatory latency. Brief assessment procedures are delineated and validated diagnostic and treatment questionnaires are reviewed. Finally, the best practices treatment recommendations are presented to guide clinicians, both familiar and unfamiliar with PE, in facilitating treatment of their patients. Development of guidelines is an evolutionary process that continually reviews data and incorporates the best new research. We expect that ongoing research will lead to a more complete understanding of the pathophysiology as well as new efficacious and safe treatments for this sexual dysfunction. Therefore, it is strongly recommended that these guidelines be re-evaluated and updated by the ISSM every 4 years.


Gene expression in fixed tissues and outcome in hepatocellular carcinoma.
It is a challenge to identify patients who, after undergoing potentially curative treatment for hepatocellular carcinoma, are at greatest risk for recurrence. Such high-risk patients could receive novel interventional measures. An obstacle to the development of genome-based predictors of outcome in patients with hepatocellular carcinoma has been the lack of a means to carry out genomewide expression profiling of fixed, as opposed to frozen, tissue. We aimed to demonstrate the feasibility of gene-expression profiling of more than 6000 human genes in formalin-fixed, paraffin-embedded tissues. We applied the method to tissues from 307 patients with hepatocellular carcinoma, from four series of patients, to discover and validate a gene-expression signature associated with survival. The expression-profiling method for formalin-fixed, paraffin-embedded tissue was highly effective: samples from 90% of the patients yielded data of high quality, including samples that had been archived for more than 24 years. Gene-expression profiles of tumor tissue failed to yield a significant association with survival. In contrast, profiles of the surrounding nontumoral liver tissue were highly correlated with survival in a training set of tissue samples from 82 Japanese patients, and the signature was validated in tissues from an independent group of 225 patients from the United States and Europe (P=0.04). We have demonstrated the feasibility of genomewide expression profiling of formalin-fixed, paraffin-embedded tissues and have shown that a reproducible gene-expression signature correlated with survival is present in liver tissue adjacent to the tumor in patients with hepatocellular carcinoma.


Noise suppressed optical diffraction tomography with autofocus correction.
We propose a novel tomographic measurement approach that enables a noise suppressed characterization of microstructures. The idea of this work is based on a finding that coherent noise in the input phase data generates an artificial circular structure whose magnitude is the highest at the centre of tomographic reconstruction. This method decreases the noise level by applying an unconventional tomographic measurement configuration with an object deliberately shifted with respect to the rotation axis. This enables a spatial separation between the reconstructed sample structure and the area of the largest refractive index perturbations. The input phase data defocusing that is a by-product of the introduced modification is numerically corrected with an automatic focus correction algorithm. The proposed method is validated with simulations and experimental measurements of an optical microtip.


A web-based nutrition program reduces health care costs in employees with cardiac risk factors: before and after cost analysis.
Rising health insurance premiums represent a rapidly increasing burden on employer-sponsors of health insurance and their employees. Some employers have become proactive in managing health care costs by providing tools to encourage employees to directly manage their health and prevent disease. One example of such a tool is DASH for Health, an Internet-based nutrition and exercise behavior modification program. This program was offered as a free, opt-in benefit to US-based employees of the EMC Corporation. The aim was to determine whether an employer-sponsored, Internet-based diet and exercise program has an effect on health care costs. There were 15,237 total employees and spouses who were included in our analyses, of whom 1967 enrolled in the DASH for Health program (DASH participants). Using a retrospective, quasi-experimental design, study year health care costs among DASH participants and non-participants were compared, controlling for baseline year costs, risk, and demographic variables. The relationship between how often a subject visited the DASH website and health care costs also was examined. These relationships were examined among all study subjects and among a subgroup of 735 subjects with cardiovascular conditions (diabetes, hypertension, hyperlipidemia). Multiple linear regression analysis examined the relationship of program use to health care costs, comparing study year costs among DASH participants and non-participants and then examining the effects of increased website use on health care costs. Analyses were repeated among the cardiovascular condition subgroups. Overall, program use was not associated with changes in health care costs. However, among the cardiovascular risk study subjects, health care costs were US$827 lower, on average, during the study year (P= .05; t(729) = 1.95). Among 1028 program users, increased website use was significantly associated with lower health care costs among those who visited the website at least nine times during the study year (US$14 decrease per visit; P = .04; t(1022) = 2.05), with annual savings highest among 80 program users with targeted conditions (US$55 decrease per visit; P < .001; t(74) = 2.71). An employer-sponsored, Internet-based diet and exercise program shows promise as a low-cost benefit that contributes to lower health care costs among persons at higher risk for above-average health care costs and utilization.


Study of Autophagy and Microangiopathy in Sural Nerves of Patients with Chronic Idiopathic Axonal Polyneuropathy.
Twenty-five percent of polyneuropathies are idiopathic. Microangiopathy has been suggested to be a possible pathogenic cause of chronic idiopathic axonal polyneuropathy (CIAP). Dysfunction of the autophagy pathway has been implicated as a marker of neurodegeneration in the central nervous system, but the autophagy process is not explored in the peripheral nervous system. In the current study, we examined the presence of microangiopathy and autophagy-related structures in sural nerve biopsies of 10 patients with CIAP, 11 controls with inflammatory neuropathy and 10 controls without sensory polyneuropathy. We did not find any significant difference in endoneurial microangiopathic markers in patients with CIAP compared to normal controls, though we did find a correlation between basal lamina area thickness and age. Unexpectedly, we found a significantly larger basal lamina area thickness in patients with vasculitic neuropathy. Furthermore, we found a significantly higher density of endoneurial autophagy-related structures, particularly in patients with CIAP but also in patients with inflammatory neuropathy, compared to normal controls. It is unclear if the alteration in the autophagy pathway is a consequence or a cause of the neuropathy. Our results do not support the hypothesis that CIAP is primarily caused by a microangiopathic process in endoneurial blood vessels in peripheral nerves. The significantly higher density of autophagy structures in sural nerves obtained from patients with CIAP and inflammatory neuropathy vs. controls indicates the involvement of this pathway in neuropathy, particularly in CIAP, since the increase in density of autophagy-related structures was more pronounced in patients with CIAP than those with inflammatory neuropathy. To our knowledge this is the first report investigating signs of autophagy process in peripheral nerves in patients with CIAP and inflammatory neuropathy.


Functional circuitry of neuro-immune communication in the mesenteric lymph node and spleen.
The peripheral nervous system is an active participant in immune responses capable of blocking aberrant activation of a variety of immune cells. As one of these neuro-immune circuits, the cholinergic anti-inflammatory pathway has been well established to reduce the severity of several immunopathologies. While the activation of this pathway by vagal nerve stimulation requires sympathetic innervation of the spleen, the neuro-immune circuitry remains highly controversial. Neuro-immune pathways in other lymphoid tissues such as mesenteric lymph nodes (MLN) that are critical to the surveillance of the small intestine and proximal colon have not been assessed. Using conditionally expressed Channelrhodopsin, selective stimulation of sympathetic post-ganglionic neurons in the superior mesenteric ganglion (SMG) prevented macrophage activation and LPS-induced TNFα production in the spleen and MLN, but not in the inguinal LN. Site selective stimulation of the SMG induced the release of norepinephrine, resulting in β2AR dependent acetylcholine release in the MLN and spleen. VNS-evoked release of norepinephrine and acetylcholine in the MLN and spleen was significantly reduced using selective optogenetic blockade applied at the SMG. Additionally, this optogenetic blockade restored LPS-induced TNFα production, despite VNS. These studies identify the superior mesenteric ganglion as a critical node in a neuro-immune circuit that can inhibit immune function in the MLN and the spleen.


Arsenate Accumulation, Distribution, and Toxicity Associated with Titanium Dioxide Nanoparticles in Daphnia magna.
Titanium dioxide nanoparticles (nano-TiO2) are widely used in consumer products. Nano-TiO2 dispersion could, however, interact with metals and modify their behavior and bioavailability in aquatic environments. In this study, we characterized and examined arsenate (As(V)) accumulation, distribution, and toxicity in Daphnia magna in the presence of nano-TiO2. Nano-TiO2 acts as a positive carrier, significantly facilitating D. magna's ability to uptake As(V). As nano-TiO2 concentrations increased from 2 to 20 mg-Ti/L, total As increased by a factor of 2.3 to 9.8 compared to the uptake from the dissolved phase. This is also supported by significant correlations between arsenic (As) and titanium (Ti) signal intensities at concentrations of 2.0 mg-Ti/L nano-TiO2 (R = 0.676, P < 0.01) and 20.0 mg-Ti/L nano-TiO2 (R = 0.776, P < 0.01), as determined by LA-ICP-MS. Even though As accumulation increased with increasing nano-TiO2 concentrations in D. magna, As(V) toxicity associated with nano-TiO2 exhibited a dual effect. Compared to the control, the increased As was mainly distributed in BDM (biologically detoxified metal), but Ti was mainly distributed in MSF (metal-sensitive fractions) with increasing nano-TiO2 levels. Differences in subcellular distribution demonstrated that adsorbed As(V) carried by nano-TiO2 could dissociate itself and be transported separately, which results in increased toxicity at higher nano-TiO2 concentrations. Decreased As(V) toxicity associated with lower nano-TiO2 concentrations results from unaffected As levels in MSFs (when compared to the control), where several As components continued to be adsorbed by nano-TiO2. Therefore, more attention should be paid to the potential influence of nano-TiO2 on bioavailability and toxicity of cocontaminants.


Italian version of Dyspnoea-12: cultural-linguistic validation, quantitative and qualitative content validity study.
Dyspnoea-12 is a valid and reliable scale to assess dyspneic symptom, considering its severity, physical and emotional components. However, it is not available in Italian version due to it was not yet translated and validated. For this reason, the aim of this study was to develop an Italian version Dyspnoea-12, providing a cultural and linguistic validation, supported by the quantitative and qualitative content validity. This was a methodological study, divided into two phases: phase one is related to the cultural and linguistic validation, phase two is related to test the quantitative and qualitative content validity. Linguistic validation followed a standardized translation process. Quantitative content validity was assessed computing content validity ratio (CVR) and index (I-CVIs and S-CVI) from expert panellists response. Qualitative content validity was assessed by the narrative analysis on the answers of three open-ended questions to the expert panellists, aimed to investigate the clarity and the pertinence of the Italian items. The translation process found a good agreement in considering clear the items in both the six involved bilingual expert translators and among the ten voluntary involved patients. CVR, I-CVIs and S-CVI were satisfactory for all the translated items. This study has represented a pivotal step to use Dyspnoea-12 amongst Italian patients. Future researches are needed to deeply investigate the Italian version of Dyspnoea-12 construct validity and its reliability, and to describe how dyspnoea components (i.e. physical and emotional) impact the life of patients with cardiorespiratory diseases.


Effects of dexamphetamine-induced dopamine release on resting-state network connectivity in recreational amphetamine users and healthy controls.
Dexamphetamine (dAMPH) is not only used for the treatment of attention deficit hyperactivity disorder (ADHD), but also as a recreational drug. Acutely, dAMPH induces release of predominantly dopamine (DA) in the striatum, and in the cortex both DA and noradrenaline. Recent animal studies have shown that chronic dAMPH administration can induce changes in the DA system following long-term exposure, as evidenced by reductions in DA transporters, D2/3 receptors and endogenous DA levels. However, only a limited number of studies have investigated the effects of dAMPH in the human brain. We used a combination of resting-state functional magnetic resonance imaging (rs-fMRI) and [(123)I]IBZM single-photon emission computed tomography (SPECT) (to assess baseline D2/3 receptor binding and DA release) in 15 recreational AMPH users and 20 matched healthy controls to investigate the short-, and long-term effects of AMPH before and after an acute intravenous challenge with dAMPH. We found that acute dAMPH administration reduced functional connectivity in the cortico-striatal-thalamic network. dAMPH-induced DA release, but not DA D2/3 receptor binding, was positively associated with connectivity changes in this network. In addition, acute dAMPH reduced connectivity in default mode networks and salience-executive-networks networks in both groups. In contrast to our hypothesis, no significant group differences were found in any of the rs-fMRI networks investigated, possibly due to lack of sensitivity or compensatory mechanisms. Our findings thus support the use of ICA-based resting-state functional connectivity as a tool to investigate acute, but not chronic, alterations induced by dAMPH on dopaminergic processing in the striatum.


Effects of dietary supplements on the space radiation-induced reduction in total antioxidant status in CBA mice.
In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by proton, HZE-particle and gamma radiation in CBA mice. The results demonstrated that the plasma level of TAS was significantly decreased (P < 0.05) in CBA mice after exposure to a 50-cGy dose of radiation from HZE particles or a 3-Gy dose of radiation from protons or gamma rays. Diet supplementation with Bowman-Birk Inhibitor Concentrate (BBIC), L-selenomethionine (L-SeM), or a combination of N-acetyl cysteine, sodium ascorbate, co-enzyme Q10 (CoQ10), alpha-lipoic acid, L-SeM and vitamin E succinate could partially or completely prevent the reduction in the plasma level of TAS in CBA mice exposed to proton or HZE-particle radiation. The selected antioxidant combination with or without CoQ10 has a comparable protective effect on the gamma-radiation-induced drop in TAS in CBA mice. These results indicate that BBIC, L-SeM and the selected antioxidant combinations may serve as countermeasures for space radiation-induced adverse biological effects.


Prognostic Factors Influencing the Outcome of 64 Consecutive Patients Undergoing Surgery for Metastatic Melanoma of the Spine.
Melanoma metastases to the spine remain a challenge for neurosurgeons. To identify factors associated with survival in a series of patients who underwent spinal surgery for metastatic melanoma. We retrospectively reviewed all patients (n = 64) who received surgical intervention for melanoma metastases to the spine at the University of Texas MD Anderson Cancer Center between July 1993 and March 2012. No patients were excluded from the study, and vital status data were available for all patients. Median overall survival was 5.7 months (95% confidence interval, 2.7-28.7). On univariate survival analysis, diagnosis of spinal metastasis after prior diagnosis of systemic metastasis, higher total spinal disease burden (including but not exclusive to the operative site), presence of progressive systemic disease at the moment of spine surgery, and postoperative complications were associated with poorer overall survival, whereas the presence of only bone metastasis at the moment of surgery was associated with improved overall survival. On multivariate survival analysis, both progressive systemic disease at the moment of spine surgery and total spinal disease burden of ≥3 vertebral levels were significantly associated with worse overall survival (hazard ratio, 6.00; 95% confidence interval, 3.19-11.28; P < .001; and hazard ratio, 2.87; 95% confidence interval, 1.62-5.07; P < .001, respectively). On multivariate analysis, involvement of ≥3 vertebral bodies and progressive systemic disease were associated with worse overall survival. Consideration of these factors should influence surgical decision making in this patient population.


Tumour necrosis factor and interleukin 6 production during interaction between activated CD4+ lymphocytes and simian immunodeficiency virus-infected macrophages.
The mechanism for the gradual loss of CD4+ T lymphocytes and the development of the slowly progressive inflammatory/degenerative lesions that accompany human immunodeficiency virus infection are poorly understood. Using the Simian immunodeficiency virus (SIVmac) macaque model of AIDS, we found that persistently infected primary macrophages fuse with primary activated CD4+ lymphocytes and that this interaction results in production of tumour necrosis factor-alpha (TNF alpha) and interleukin 6 (IL-6). An earlier report had shown that SIV-infected macaque macrophages fuse with CEM174 cells (a human CD4+ cell line) and cause their lysis. In the present report, we have shown that TNF-alpha and IL-6 are also produced during the early stages of this interaction. Data from cocultivation of infected macrophages with several CD4+ T cell lines, including CEM174, suggested that the cytokines are produced by the T cells, and that cytokine production is restricted to those cells which not only express CD4, but are also capable of fusing with the infected macrophages. These data suggest that infected macrophages in vivo could fuse with and eliminate activated CD4+ lymphocytes and, during this interaction, release cytokines, which would contribute to the degenerative and inflammatory lesions characteristic of this disease.


The Effect of Coffee and Quantity of Consumption on Specific Cardiovascular and All-Cause Mortality: Coffee Consumption Does Not Affect Mortality.
Previous studies have examined whether or not an association exists between the consumption of caffeinated coffee to all-cause and cardiovascular mortality. This study aimed to delineate this association using population representative data from the National Health and Nutrition Examination Survey III. Patients were included in the study if all the following criteria were met: (1) follow-up mortality data were available, (2) age of at least 45 years, and (3) reported amount of average coffee consumption. A total of 8608 patients were included, with patients stratified into the following groups of average daily coffee consumption: (1) no coffee consumption, (2) less than 1 cup, (3) 1 cup a day, (4) 2-3 cups, (5) 4-5 cups, (6) more than 6 cups a day. Odds ratios, 95% confidence intervals, and P values were calculated for univariate analysis to compare the prevalence of all-cause mortality, ischemia-related mortality, congestive heart failure-related mortality, and stroke-related mortality, using the no coffee consumption group as reference. These were then adjusted for confounding factors for a multivariate analysis. P < 0.05 were considered statistically significant. Univariate analysis demonstrated an association between coffee consumption and mortality, although this became insignificant on multivariate analysis. Coffee consumption, thus, does not seem to impact all-cause mortality or specific cardiovascular mortality. These findings do differ from those of recently published studies. Coffee consumption of any quantity seems to be safe without any increased mortality risk. There may be some protective effects but additional data are needed to further delineate this.


Diagnostic implications of podoplanin expression in peripheral nerve sheath neoplasms.
By using the D2-40 antibody, we have observed podoplanin expression in Schwann cells and perineurial cells. Podoplanin expression has not been well characterized in peripheral nerve sheath tumors. Because neoplasms of neural crest lineage, including peripheral nerve sheath and melanocytic neoplasms, may share histologic and immunohistochemical characteristics, we evaluated podoplanin and S-100 expression in these lesions to determine the usefulness of podoplanin as a diagnostic marker. Diffuse podoplanin and S-100 expression was observed in 16 (76%) of 21 classical schwannomas, 6 (100%) of 6 cellular schwannomas, and 3 (75%) of 4 epithelioid malignant peripheral nerve sheath tumors (EMPNSTs). Podoplanin was expressed in 3 (7%) of 43 neurofibromas, 16 (21%) of 75 spindle cell MPNSTs (SMPNSTs), and 1 (10%) of 10 spindle cell melanomas but was absent in conventional melanoma. Only rare neurofibromas and SMPNSTs showed strong coexpression of podoplanin and S-100. These results suggest diffuse podoplanin expression or coexpression of podoplanin and S-100 is limited to schwannoma and EMPNST and may be useful in the evaluation of these neoplasms.


Emergence of extended-spectrum-beta-lactamase (CTX-M-9)-producing multiresistant strains of Salmonella enterica serotype Virchow in poultry and humans in France.
During 2002 to 2003, eight Salmonella enterica serotype Virchow poultry and poultry product isolates from various sources (chicken farms, poultry slaughterhouse, or retail store) and one S. enterica rough strain isolated from human feces were found to produce extended-spectrum beta-lactamase CTX-M-9. Poultry and poultry product isolates were recovered from different locations in the southwest of France. The human rough isolate had sequences of flagellin genes (fliC and fljB) typical of serotype Virchow and ribotyping and pulsed-field gel electrophoresis (PFGE) patterns closely similar to those of serotype Virchow strains. PFGE confirmed the clonal relationship between the poultry isolates, while the human isolate displayed a pattern with 94% homology. The bla(CTX-M-9) gene was located on a conjugative plasmid and was shown to be linked to orf513. Plasmid profiling found a very similar EcoRI restriction pattern in six transconjugants studied, including transconjugants obtained from the human isolate. A single hatchery, supplying chicks to the six farms, was identified. Emergence of extended-spectrum beta-lactamase-producing S. enterica strains in food animals is a major concern, as such strains could disseminate on a large scale and lead to antibiotic therapy difficulties.


SU-E-J-93: Fourier Transform-Based Medical Image Registration.
To evaluate the use of a Fast Fourier Transform (FFT) based pattern-matching algorithm for two-dimensional translational and rotational medical image registration. The FFT pattern matching algorithm is based on the Fourier shift theorem. Briefly, image registration is accomplished by obtaining the Fourier Transform (FT) of two images, taking the normalized cross-correlation of the two FT, and performing an inverse FT on this correlation matrix. This results in a Dirchlet delta function that has a maximum value at a location corresponding to the translational shift between the two images. Rotational registration can also be achieved by performing this algorithm on the polar transformation of the FT images. The FT registration method was evaluated through the use of clinical images with induced translational and rotational shifts. Over a range of induced shifts of +/-10 mm in both the x and y directions, and induced rotations of +/-10 degrees, all recovered rotations were within 0.1 degree of the induced rotation, and all recovered translations were within 0.5 mm of the induced translation. The computational time of the FT registration on a 1024×1024 image was approximately 2.23 sec. An FFT based image registration algorithm is computationally efficient and provides a high degree of accuracy for two dimensional image registrations. The FFT registration approach provides a distinct analytical solution and does not rely on iterative methods to converge on a solution. In addition, the discrete nature of the FFT means that the accuracy of the solution is directly related to the size of the pixels in the images. The equivalent of sub-pixel registration can be achieved by simply resizing the image to a larger matrix (i.e. 512×512 to 1024×1024).


Intraperitoneal resuscitation improves intestinal blood flow following hemorrhagic shock.
To study the effects of peritoneal resuscitation from hemorrhagic shock. Methods for conventional resuscitation (CR) from hemorrhagic shock (HS) often fail to restore adequate intestinal blood flow, and intestinal ischemia has been implicated in the activation of the inflammatory response. There is clinical evidence that intestinal hypoperfusion is a major factor in progressive organ failure following HS. This study presents a novel technique of peritoneal resuscitation (PR) that improves visceral perfusion. Male Sprague-Dawley rats were bled to 50% of baseline mean arterial pressure (MAP) and resuscitated with shed blood plus 2 equal volumes of saline (CR). Groups were 1) sham, 2) HS + CR, and 3) HS + CR + PR with a hyperosmolar dextrose-based solution (Delflex 2.5%). Groups 1 and 2 had normal saline PR. In vivo videomicroscopy and Doppler velocimetry were used to assess terminal ileal microvascular blood flow. Endothelial cell function was assessed by the endothelium-dependent vasodilator acetylcholine. Despite restored heart rate and MAP to baseline values, CR animals developed a progressive intestinal vasoconstriction and tissue hypoperfusion compared to baseline flow. PR induced an immediate and sustained vasodilation compared to baseline and a marked increase in average intestinal blood flow during the entire 2-hour post-resuscitation period. Endothelial-dependent dilator function was preserved with PR. Despite the restoration of MAP with blood and saline infusions, progressive vasoconstriction and compromised intestinal blood flow occurs following HS/CR. Hyperosmolar PR during CR maintains intestinal blood flow and endothelial function. This is thought to be a direct effect of hyperosmolar solutions on the visceral microvessels. The addition of PR to a CR protocol prevents the splanchnic ischemia that initiates systemic inflammation.


Normalization of Plus Size and the Danger of Unseen Overweight and Obesity in England.
This study aimed to investigate trends and sociodemographic factors underlying weight misperception in adults with overweight and obesity in England. This study used descriptive and logistic regression analyses based on a pooled nationally representative cross-sectional survey, Health Survey for England, for the years 1997, 1998, 2002, 2014, and 2015 of individuals with BMI ≥ 25 (n = 23,459). The main outcomes were (1) weight misperception and (2) weight-loss attempts as well as the associations with demographic and socioeconomic characteristics and health status. The proportion of individuals with overweight and obesity misperceiving their weight status increased over time between 1997 and 2015 (37% to 40% in men; 17% to 19% in women). There were socioeconomic disparities in the misperception of weight status, with lower-educated individuals from poorer-income households and members of minority ethnic groups being more likely to underestimate their weight. Those underestimating their overweight and obesity status were 85% less likely to try to lose weight compared with people who accurately identified their weight status. The upward trend in underassessment of overweight and obesity status in England is possibly a result of the normalization of overweight and obesity. Obesity prevention programs need to consider differential sociodemographic characteristics associated with underassessment of weight status.


Topological constraints on transvection between white genes within the transposing element TE35B in Drosophila melanogaster.
The transposable element TE35B carries two copies of the white (w) gene at 35B1.2 on the second chromosome. These w genes are suppressed in zeste-1 (z1) mutant background in a synapsis-dependent manner. Single-copy derivatives of the original TE35B stock give red eyes when heterozygous, but zeste eyes when homozygous. TE35B derivatives carrying single, double or triple copies of w were crossed to generate flies carrying from two to five ectopic w genes. Within this range, z1-mediated suppression is insensitive to copynumber and does not distinguish between w genes that are in cis or in trans. Suppression does not require the juxtaposition of even numbers of w genes, but is extremely sensitive to chromosomal topology. When arranged in a tight cluster, in triple-copy TE derivatives, w genes are nonsuppressible. Breakpoints falling within TE35B and separating two functional w genes act as partial suppressors of z1. Similarly, breakpoints immediately proximal or distal to both w genes give partial suppression. This transvection-dependent downregulation of w genes may result from mis-activation of the X-chromosome dosage compensation mechanism.


Living donor kidney transplantation: the donor profile in Trinidad and Tobago.
The National Organ Transplant Unit (NOTU) of Trinidad and Tobago, first implemented in January 2006, was mandated to facilitate renal and corneal transplantation. Since then, 60 transplants have been performed utilizing living kidney donors. The aim of this study is to ascertain the typical donor profile and to highlight the safety involved with live kidney donation. This descriptive study utilized the medical records of 60 consecutive live kidney donors between the period January 2006 and May 2010. Donor information was recorded on Microsoft Excel spreadsheets and analysed using the Statistical Package for Social Sciences 12.0. Among the 60 donors, males and females were in equal proportions with a mean age of 35.0 (+/- 10.7) years; a mean body mass index (BMI) of 25.8 (+/- 4.2) kg/m2 and 48.3% were of East Indian decent. The majority of donors were related to the recipient (71.7%). At donation, the mean creatinine was 84.9 (+/- 17.7) micromol/L, average urine creatinine clearance, 1.83 (+/- 0.53) mL/s and mean 24 hour urine protein, 141.8 (+/- 78.6) mg. There was a significant association between the BMI at donation and proteinuria one year after donation (p = 0.043). The average hospital stay was 5.0 (+/- 0.95) days with minimal postoperative complications. The typical live kidney donor in Trinidad and Tobago is a 35-year-old, slightly overweight male or female who is usually of East Indian decent, donating a kidney to a relative. Living kidney donation in this transplant unit is safe with minimal short-term complications.


A Multi-Rater Latent Growth Curve Model.
To avoid the subjectivity of having a single person evaluate a construct of interest (e.g., a student's self-efficacy in school), multiple raters are often used. Increasingly, data that use multiple raters to evaluate psychological and social-emotional constructs over time are available. While a range of models to address measurement issues that arise when using multiple raters have been presented, including a small number for longitudinal data, few if any models are available to estimate growth in the presence of multiple raters. In this study, we provide a model that removes all but the shared perceptions of raters at a given timepoint (i.e., removes unique rater variance), then adds on a latent growth curve model across timepoints. Through simulation and empirical studies, we examine the performance of the model in terms of recovering true growth parameters, and relative to more crude approaches like estimating growth based on a single rater. Our results indicate that the model we propose performs quite well along these dimensions, and shows promise for use by researchers who want to estimate growth based on longitudinal multi-rater data.


Tracking a medically important spider: climate change, ecological niche modeling, and the brown recluse (Loxosceles reclusa).
Most spiders use venom to paralyze their prey and are commonly feared for their potential to cause injury to humans. In North America, one species in particular, Loxosceles reclusa (brown recluse spider, Sicariidae), causes the majority of necrotic wounds induced by the Araneae. However, its distributional limitations are poorly understood and, as a result, medical professionals routinely misdiagnose brown recluse bites outside endemic areas, confusing putative spider bites for other serious conditions. To address the issue of brown recluse distribution, we employ ecological niche modeling to investigate the present and future distributional potential of this species. We delineate range boundaries and demonstrate that under future climate change scenarios, the spider's distribution may expand northward, invading previously unaffected regions of the USA. At present, the spider's range is centered in the USA, from Kansas east to Kentucky and from southern Iowa south to Louisiana. Newly influenced areas may include parts of Nebraska, Minnesota, Wisconsin, Michigan, South Dakota, Ohio, and Pennsylvania. These results illustrate a potential negative consequence of climate change on humans and will aid medical professionals in proper bite identification/treatment, potentially reducing bite misdiagnoses.