Variable selection in Logistic regression model with genetic algorithm.
Variable or feature selection is one of the most important steps in model specification. Especially in the case of medical-decision making, the direct use of a medical database, without a previous analysis and preprocessing step, is often counterproductive. In this way, the variable selection represents the method of choosing the most relevant attributes from the database in order to build a robust learning models and, thus, to improve the performance of the models used in the decision process. In biomedical research, the purpose of variable selection is to select clinically important and statistically significant variables, while excluding unrelated or noise variables. A variety of methods exist for variable selection, but none of them is without limitations. For example, the stepwise approach, which is highly used, adds the best variable in each cycle generally producing an acceptable set of variables. Nevertheless, it is limited by the fact that it commonly trapped in local optima. The best subset approach can systematically search the entire covariate pattern space, but the solution pool can be extremely large with tens to hundreds of variables, which is the case in nowadays clinical data. Genetic algorithms (GA) are heuristic optimization approaches and can be used for variable selection in multivariable regression models. This tutorial paper aims to provide a step-by-step approach to the use of GA in variable selection. The R code provided in the text can be extended and adapted to other data analysis needs.


Effect of synbiotic pomegranate juice on glycemic, sex hormone profile and anthropometric indices in PCOS: A randomized, triple blind, controlled trial.
Polycystic Ovarian Syndrome is a common reproductive, endocrine, and metabolic disease in women. Pomegranate juice, known as a rich source of phytochemicals with high antioxidant activity, enriched with probiotic may improve PCOS. A randomized, controlled, triple-blinded, parallel trial study was performed in PCOS patients (n = 92). Three treatment groups (23 patients each) received 2 L of synbiotic pomegranate juice (SPJ), pomegranate juice (PJ), and synbiotic beverage (SB) weekly. The control group (23 patients) received 2 L of placebo beverage weekly. Primary outcome was any change in insulin resistance and secondary outcomes were fasting blood sugar (FBS), insulin sensitivity, testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), body mass index (BMI), waist and hip circumference, from baseline to the end of the trial. At the end of the study, 86 patients were analyzed. There was significant change in insulin resistance in the SPJ and SB groups. Insulin sensitivity increased significantly in the SPJ and SB groups. Insulin also changed significantly in the SPJ and SB groups. BMI, weight and waist circumference decreased significantly in the SPJ and SB groups. Testosterone level also decreased significantly in the SPJ and SB groups. There was no significant change in FPG, LH and FSH in any of the groups. SPJ in the form of a new beverage can improve insulin resistance, insulin, testosterone level, BMI, weight and waist circumference in PCOS. This trial was registered in Iranian Registry of Clinical Trials, with number: 25272.


Impact of rehabilitation on self-concept following traumatic brain injury: An exploratory systematic review of intervention methodology and efficacy.
To date, reviews of rehabilitation efficacy after traumatic brain injury (TBI) have overlooked the impact on sense of self, focusing instead on functional impairment and psychological distress. The present review sought to address this gap by critically appraising the methodology and efficacy of intervention studies that assess changes in self-concept. A systematic search of PsycINFO, Medline, CINAHL and PubMed was conducted from inception to September 2013 to identify studies reporting pre- and post-intervention changes on validated measures of self-esteem or self-concept in adults with TBI. Methodological quality of randomised controlled trials (RCTs) was examined using the Physiotherapy Evidence Database (PEDro) scale. A total of 17 studies (10 RCTs, 4 non-RCT group studies, 3 case studies) was identified, which examined the impact of psychotherapy, family-based support, cognitive rehabilitation or activity-based interventions on self-concept. The findings on the efficacy of these interventions were mixed, with only 10 studies showing some evidence of improvement in self-concept based on within-group or pre-post comparisons. Such findings highlight the need for greater focus on the impact of rehabilitation on self-understanding with improved assessment and intervention methodology. We draw upon theories of identity reconstruction and highlight implications for the design and evaluation of identity-oriented interventions that can supplement existing rehabilitation programmes for people with TBI.


Interactions between dorsal root axons and their target motor neurons in developing mammalian spinal cord.
We have utilized the lipid-soluble tracers Dil and DiA to investigate interactions between group la dorsal root afferent axons and their target motor neurons in developing rat spinal cord. We show here that la axons project toward motor pools in fascicles that exhibit a considerable degree of spatial order. A rough topography is present in that axons that innervate medially located axial motor neurons cross over others in the intermediate zone and follow a separate path along the midline toward their appropriate targets. Surprisingly, we have also found that motor neuron dendritic projections are well established in the transverse plane prior to the arrival of la afferents. Although dendrites from motor pools innervating limb muscles project directly in the path of incoming la afferents, they do not guide afferents to appropriate motor pools. The la afferents pass over the distal dendrites and grow all the way to the border between gray and developing white matter. A significant amount of terminal branching and bouton formation is in the vicinity of motor neuron somata and proximal regions of the dendritic arbors. Few boutons are found near dendrites that project dorsal to the motor pools, and virtually no boutons are found on dendrites in white matter. Our results show that la afferent axons are not guided to appropriate motor pools by random encounters with motor dendrites, and raise the possibility that mechanisms exist that promote an orderly projection of la afferents to particular regions of the ventral horn. The striking lack of innervation of white matter and dorsally directed dendrites by la afferents raises the question of whether descending and intersegmental systems have their initial interactions with these regions of the motor neuron dendritic arbor.


Culture, socioeconomic status, and physical and mental health in Brazil.
The association of socioeconomic variables with poor health status has been widely observed, if not well understood, and cultural dimensions of socioeconomic differences have rarely been incorporated into research models. In this article, a cultural dimension of socioeconomic status is examined in a Brazilian city through the use of ethnographic and social survey techniques. It suggests that lifestyle, defined in terms of the relative ability to accumulate consumer goods and the adoption of associated behaviors, is an important component of socioeconomic differences. Further research using cultural consensus analysis, a structured ethnographic technique that may be used to study shared cultural knowledge, demonstrates significant consensus regarding the definition of the successful lifestyle. Then, using that culturally defined model of the successful lifestyle as the central tendency, an individual-level measure of approximation to that lifestyle was developed for a representative sample of 250 persons. This culturally defined measure of lifestyle was inversely associated with arterial blood pressure (beta = -.216, p < .01), depressive symptoms (beta = -.236, p < .01), and globally perceived stress (beta = -.358, p < .01); furthermore, it absorbed the explained variability in these outcomes that is associated with conventional socioeconomic variables (occupation, education, income). For arterial pressure, cultural consonance explained almost 10 percent of the differences in blood pressure between individuals; for the psychological outcome variables, cultural consonance explained between 10 percent and 20 percent of the differences between individuals. Finally, its statistical effects were independent of other socioeconomic, dietary, anthropometric, and psychosocial variables. These results suggest that an individual's approximation to the cultural ideal of lifestyle, his or her "cultural consonance," mediates the observed effects of socioeconomic variables on health status.


Removal of toxic metals using endocarp of açaí berry as biosorbent.
The effectiveness of açaí endocarp as biosorbent for removal of Cd2+, Pb2+ and Cr3+ from single solute solutions was analyzed. The biomass of açaí endocarp was characterized by scanning electron microscopy, infrared spectroscopy and determining the point of zero charge. The optimum conditions for adsorption process were obtained at solution pH 6.0 for Cd(II) removal, pH 5.0 for Pb(II) removal, and, pH 4.0 for Cr(III). Furthermore, the average optimum efficiency of biosorbent in the optimum conditions was 8, 20 and 12 g of biosorbent per litre of contaminant solution, respectively, for Cd(II), Pb(II) and Cr(III). The best dynamic equilibrium time was reached at 60 min and Langmuir's model had the best fit for Cd(II) and Cr(III) biosorption, indicating a monolayer adsorption. Freundlich's model exhibited the best fit for Pb(II) ion. Elution rates were low, indicating a strong metal interaction with the adsorbent's surface. Thermodynamic parameters showed a spontaneous and endothermal process in the case of Cd(II) and Pb(II) ions, but not for Cr(III) ion, which appears to be an exothermic process. Results show that the use of the açaí biosorbent may be a promising alternative for the remediation of polluted water, due to its low cost and highly availability.


Unraveling the role of thiosulfate sulfurtransferase in metabolic diseases.
Thiosulfate sulfurtransferase (TST, EC 22.214.171.124), also known as Rhodanese, is a mitochondrial enzyme which catalyzes the transfer of sulfur in several molecular pathways. After its initial identification as a cyanide detoxification enzyme, it was found that its functions also include sulfur metabolism, modification of iron‑sulfur clusters and the reduction of antioxidants glutathione and thioredoxin. TST deficiency was shown to be strongly related to the pathophysiology of metabolic diseases including diabetes and obesity. This review summarizes research related to the enzymatic properties and functions of TST, to then explore the association between the effects of TST on mitochondria and development of diseases such as diabetes and obesity.


Structural issues affecting mixed methods studies in health research: a qualitative study.
Health researchers undertake studies which combine qualitative and quantitative methods. Little attention has been paid to the structural issues affecting this mixed methods approach. We explored the facilitators and barriers to undertaking mixed methods studies in health research. Face-to-face semi-structured interviews with 20 researchers experienced in mixed methods research in health in the United Kingdom. Structural facilitators for undertaking mixed methods studies included a perception that funding bodies promoted this approach, and the multidisciplinary constituency of some university departments. Structural barriers to exploiting the potential of these studies included a lack of education and training in mixed methods research, and a lack of templates for reporting mixed methods articles in peer-reviewed journals. The 'hierarchy of evidence' relating to effectiveness studies in health care research, with the randomised controlled trial as the gold standard, appeared to pervade the health research infrastructure. Thus integration of data and findings from qualitative and quantitative components of mixed methods studies, and dissemination of integrated outputs, tended to occur through serendipity and effort, further highlighting the presence of structural constraints. Researchers are agents who may also support current structures - journal reviewers and editors, and directors of postgraduate training courses - and thus have the ability to improve the structural support for exploiting the potential of mixed methods research. The environment for health research in the UK appears to be conducive to mixed methods research but not to exploiting the potential of this approach. Structural change, as well as change in researcher behaviour, will be necessary if researchers are to fully exploit the potential of using mixed methods research.


Relative abundance of and composition within fungal orders differ between cheatgrass (Bromus tectorum) and sagebrush (Artemisia tridentata)-associated soils.
Nonnative Bromus tectorum (cheatgrass) is decimating sagebrush steppe, one of the largest ecosystems in the Western United States, and is causing regional-scale shifts in the predominant plant-fungal interactions. Sagebrush, a native perennial, hosts arbuscular mycorrhizal fungi (AMF), whereas cheatgrass, a winter annual, is a relatively poor host of AMF. This shift is likely intertwined with decreased carbon (C)-sequestration in cheatgrass-invaded soils and alterations in overall soil fungal community composition and structure, but the latter remain unresolved. We examined soil fungal communities using high throughput amplicon sequencing (ribosomal large subunit gene) in the 0-4 cm and 4-8 cm depth intervals of six cores from cheatgrass- and six cores from sagebrush-dominated soils. Sagebrush core surfaces (0-4 cm) contained higher nitrogen and total C than cheatgrass core surfaces; these differences mirrored the presence of glomalin related soil proteins (GRSP), which has been associated with AMF activity and increased C-sequestration. Fungal richness was not significantly affected by vegetation type, depth or an interaction of the two factors. However, the relative abundance of seven taxonomic orders was significantly affected by vegetation type or the interaction between vegetation type and depth. Teloschistales, Spizellomycetales, Pezizales and Cantharellales were more abundant in sagebrush libraries and contain mycorrhizal, lichenized and basal lineages of fungi. Only two orders (Coniochaetales and Sordariales), which contain numerous economically important pathogens and opportunistic saprotrophs, were more abundant in cheatgrass libraries. Pleosporales, Agaricales, Helotiales and Hypocreales were most abundant across all libraries, but the number of genera detected within these orders was as much as 29 times lower in cheatgrass relative to sagebrush libraries. These compositional differences between fungal communities associated with cheatgrass- and sagebrush-dominated soils warrant future research to examine soil fungal community composition across more sites and time points as well as in association with native grass species that also occupy cheatgrass-invaded ecosystems.


A Comprehensive Analysis of Alternative Splicing in Paleopolyploid Maize.
Identifying and characterizing alternative splicing (AS) enables our understanding of the biological role of transcript isoform diversity. This study describes the use of publicly available RNA-Seq data to identify and characterize the global diversity of AS isoforms in maize using the inbred lines B73 and Mo17, and a related species, sorghum. Identification and characterization of AS within maize tissues revealed that genes expressed in seed exhibit the largest differential AS relative to other tissues examined. Additionally, differences in AS between the two genotypes B73 and Mo17 are greatest within genes expressed in seed. We demonstrate that changes in the level of alternatively spliced transcripts (intron retention and exon skipping) do not solely reflect differences in total transcript abundance, and we present evidence that intron retention may act to fine-tune gene expression across seed development stages. Furthermore, we have identified temperature sensitive AS in maize and demonstrate that drought-induced changes in AS involve distinct sets of genes in reproductive and vegetative tissues. Examining our identified AS isoforms within B73 × Mo17 recombinant inbred lines (RILs) identified splicing QTL (sQTL). The 43.3% of cis-sQTL regulated junctions are actually identified as alternatively spliced junctions in our analysis, while 10 Mb windows on each side of 48.2% of trans-sQTLs overlap with splicing related genes. Using sorghum as an out-group enabled direct examination of loss or conservation of AS between homeologous genes representing the two subgenomes of maize. We identify several instances where AS isoforms that are conserved between one maize homeolog and its sorghum ortholog are absent from the second maize homeolog, suggesting that these AS isoforms may have been lost after the maize whole genome duplication event. This comprehensive analysis provides new insights into the complexity of AS in maize.


Reliability and initial validation of the ulcerative colitis endoscopic index of severity.
We studied the reliability of the previously described Ulcerative Colitis Endoscopic Index of Severity (UCEIS) and validated it with an independent cohort of investigators. We created a new library of 57 videos of flexible sigmoidoscopy and stratified them based on disease severity. Twenty-five investigators were each randomly assigned to assess 28 videos (which included 4 duplicates to assess intraobserver reliability). Investigators were blinded to clinical details except for 2 of 4 duplicated videos (to assess the impact of knowledge of symptoms on assessment). Three descriptors ("vascular pattern", "bleeding", and "erosions and ulcers") comprising the UCEIS were scored with a visual analogue scale (VAS) to assess overall severity. Intrainvestigator and interinvestigator agreement was characterized by κ statistical analysis; reliability ratios were used to compare VAS and UCEIS scores. There was a high level of correlation between UCEIS scores and overall assessment of severity (correlation coefficient, 0.93). Internal consistency (Cronbach α analysis) was 0.86. Intrainvestigator and interinvestigator reliability ratios for UCEIS scores were 0.96 and 0.88, respectively. Intrainvestigator agreement in determination of the UCEIS score was good (κ = 0.72), with individual descriptors ranging from a κ of 0.47 (for bleeding) to 0.87 (for vascular pattern). Interinvestigator agreement in determination of UCEIS scores was moderate (κ = 0.50), with descriptors ranging from a κ of 0.48 (for bleeding) to 0.54 (for vascular pattern). Intrainvestigator variability in determining UCEIS scores did not change appreciably when a video was presented with clinical details. The UCEIS and its components show satisfactory intrainvestigator and interinvestigator reliability. Among investigators, the UCEIS accounted for a median of 86% of the variability in evaluation of overall severity on the VAS when assessing the endoscopic severity of UC and was unaffected by knowledge of clinical details.


Combined Endocyclophotocoagulation and Phacoemulsification in Patients with Glaucoma of African Descent.
The aim of this study was to evaluate the outcomes of combined endocyclophotocoagulation (ECP) and phacoemulsification regarding vision, refraction, intraocular pressure (IOP), medication dependence, and complications in patients of African descent. A retrospective chart review was performed including all cases of ECP combined with phacoemulsification from October 2015 to March 2017. Exclusion criteria consisted of patients who were not of African descent and patients with <1 month follow-up. IOP was the primary outcome. Thirty-two eyes of 29 patients were included in the study. Mean ± standard deviation (SD) of IOP decreased from 17.30 ± 6.30 mmHg preoperatively to 15.88 ± 4.23 mmHg at the last postoperative visit (P = 0.301). In 2 of eight patients who did not demonstrate a difference in pre- and postoperative IOP changes, all IOP lowering medications were stopped. The mean ± SD of follow-up was 5.05 ± 4.08 months with a range of 1 to 18 months. The mean ± SD number of medications used for each patient for IOP control decreased from 2.59 ± 1.01 preoperatively to 1.97 ±1.38 (P = 0.045). Average visual acuity improved from 20/50 preoperatively to 20/25 (P = 0.002). Postoperative complication rate was low. ECP combined with phacoemulsification was effective to decrease IOP lowering medication dependence in patients of African descent. We found that combined ECP and phacoemulsification can lead to a significantly decreased dependence on IOP lowering drops, with some patients demonstrating complete independence from drops following surgery. Although there was not a significant decrease in IOP postoperatively when analyzed collectively, larger studies might to find such an association. Combined ECP and phacoemulsification has been shown to be a safe combination in patients with refractive glaucoma and may be considered if a patient desire less dependence on IOP lowering drops once other first-line methods have failed, or as a bridge between conservative and more definitive surgical treatment.


Antioxidant and antidiabetic activities of 11 herbal plants from Hyrcania region, Iran.
In the present study, 2,2-diphenyl-1-picrylhydrazyl radical scavenging, α-amylase and α-glucosidase inhibition activities, and total phenolic contents of n-hexane, ethyl acetate, and methanol extracts of various parts of Allium paradoxum, Buxus hyrcana, Convolvulus persicus, Eryngium caucasicum, Heracleum persicum, Pimpinella affinis, Parrotia persica, Primula heterochroma, Pyrus boissieriana, Ruscus hyrcanus, and Smilax excelsa were investigated. These plants, which mostly serve as food flavoring, were collected from Hyrcania region, Sari, Iran. Some extracts of H. persicum, S. excels, P. boissieriana, P. persica, and P. heterochroma exhibited significant antidiabetic activities in α-amylase and α-glucosidase assays, more effective than acarbose (concentrations that cause 50% inhibition = 75.7 μg/mL and 6.1 μg/mL against α-amylase and α-glucosidase, respectively). Also, C. persicus, P. boissieriana, and P. heterochroma showed strong antioxidant activities, compared with butylated hydroxytoluene (concentration that causes 50% inhibition = 16.7 μg/mL). In conclusion, this study can recommend these plants as good candidates for further investigations to find potent antidiabetic natural products or probable lead compounds. Statistical analysis showed significant correlation between the 2,2-diphenyl-1-picrylhydrazyl scavenging activity and total phenolic contents (r = 0.711, p < 0.001).


First-in-human evaluation of a hexon chimeric adenovirus vector expressing HIV-1 Env (IPCAVD 002).
We report the first-in-human safety and immunogenicity assessment of a prototype hexon chimeric adenovirus (Ad) serotype 5 (Ad5) vector containing the hexon hypervariable regions of Ad serotype 48 (Ad48) and expressing human immunodeficiency virus (HIV) type 1 EnvA. Forty-eight Ad5 and Ad48 seronegative, HIV-uninfected subjects were enrolled in a randomized, double-blind, placebo-controlled, dose escalation phase 1 study. Four groups of 12 subjects received 10(9) to 10(11) viral particles (vp) of the Ad5HVR48.EnvA.01 vaccine (n = 10 per group) or placebo (n = 2 per group) at week 0 or weeks 0, 4, and 24. Safety and immunogenicity were assessed. Self-limited reactogenicity was observed after the initial immunization in the highest (10(11) vp) dose group. Responses in vaccinees included Ad48 neutralizing antibody (nAb) titers higher than Ad5 nAb titers, EnvA-specific enzyme-linked immunosorbent assay titers, and EnvA-specific enzyme-linked immunospot assay responses, and these responses generally persisted at week 52. At week 28 in the 10(9), 10(10), and 10(11) vp 3-dose groups, geometric mean EnvA enzyme-linked immunosorbent assay titers were 5721, 10 929, and 3420, respectively, and Ad48 nAb titers were a median of 1.7-fold higher than for Ad5. Ad5HVR48.ENVA.01 was safe, well tolerated, and immunogenic at all doses tested. Vector-elicited nAb responses were greater for Ad48 than Ad5, confirming that Ad-specific nAbs in humans are primarily, but not exclusively, directed against the hexon hypervariable regions. Clinical Trials Registration. NCT00695877.


Nutrition in hepatic encephalopathy.
Protein calorie malnutrition (PCM) is a well-known complication of chronic liver disease (CLD). A major contribution to PCM in CLD is restriction of dietary protein intake. After many decades of injudicious reduction in dietary protein, cirrhotic patients are now prescribed appropriate amounts of protein. PCM in CLD is known to be associated with life-threatening complications. In the general approach to these patients, the initial and most important step for the clinician is to recognize the extent of malnutrition. Most patients tolerate a normal amount of dietary protein without developing hepatic encephalopathy (HE). Oral branched-chain amino acids (BCAAs) have a limited role in HE. Patients who exhibit dietary protein intolerance originally were thought to be best treated with BCAA formulations. Mixed evidence has been reported in multiple studies. In keeping with other reports, this article shows that in animal protein-intolerant patients, even those with advanced cirrhosis, vegetable protein-based diets are well tolerated. Another approach to management of apparent dietary intolerance is to optimize HE treatment with available medications. This article reviews the causes of HE, minimal HE, and PCM; examines nutrition requirements and assessment; and discusses treatment options for malnutrition in HE.


Therapeutic potential of a monoclonal antibody blocking the Wnt pathway in diabetic retinopathy.
Dysregulation of Wnt/β-catenin signaling contributes to the development of diabetic retinopathy by inducing retinal inflammation, vascular leakage, and neovascularization. Here, we evaluated the inhibitory effect of a monoclonal antibody (Mab) specific for the E1E2 domain of Wnt coreceptor low-density lipoprotein receptor-related protein 6, Mab2F1, on canonical Wnt signaling and its therapeutic potential for diabetic retinopathy. Mab2F1 displayed robust inhibition on Wnt signaling with a half-maximal inhibitory concentration (IC₅₀) of 20 μg/mL in retinal pigment epithelial cells. In addition, Mab2F1 also attenuated the accumulation of β-catenin and overexpression of vascular endothelial growth factor, intercellular adhesion molecule-1, and tumor necrosis factor-α induced by high-glucose medium in retinal endothelial cells. In vivo, an intravitreal injection of Mab2F1 significantly reduced retinal vascular leakage and decreased preretinal vascular cells in oxygen-induced retinopathy (OIR) rats, demonstrating its inhibitory effects on ischemia-induced retinal neovascularization. Moreover, Mab2F1 blocked the overexpression of the inflammatory/angiogenic factors, attenuated leukostasis, and reduced retinal vascular leakage in both early and late stages of streptozotocin-induced diabetes. In conclusion, Mab2F1 inhibits canonical Wnt signaling, vascular leakage, and inflammation in the retina of diabetic retinopathy models, suggesting its potential to be used as a therapeutic agent in combination with other antiangiogenic compounds.


Cutting the cost of carbon capture: a case for carbon capture and utilization.
A significant part of the cost for carbon capture and storage (CCS) is related to the compression of captured CO2 to its supercritical state, at 150 bar and typically 99% purity. These stringent conditions may however not always be necessary for specific cases of carbon capture and utilization (CCU). In this manuscript, we investigate how much the parasitic energy of an adsorbent-based carbon capture process may be lowered by utilizing CO2 at 1 bar and adapting the final purity requirement for CO2 from 99% to 70% or 50%. We compare different CO2 sources: the flue gases of coal-fired or natural gas-fired power plants and ambient air. We evaluate the carbon capture performance of over 60 nanoporous materials and determine the influence of the initial and final CO2 purity on the parasitic energy of the carbon capture process. Moreover, we demonstrate the underlying principles of the parasitic energy minimization in more detail using the commercially available NaX zeolite. Finally, the calculated utilization cost of CO2 is compared with the reported prices for CO2 and published costs for CCS.


Impact of terrorism on the development of posttraumatic stress disorder (PTSD) among the residents of Khyber Bazaar and its immediate surrounding areas in Peshawar, Khyber Pakhtunkhwa, Pakistan.
This study evaluated the prevalence of posttraumatic stress disorder (PTSD) and the severity of PTSD symptoms in survivors, rescuers and witnesses of terrorist attacks on Khyber bazaar, Qissa Khawani bazaar, and All Saints Church in Peshawar city area. Cross-sectional survey is carried out on a sample of one hundred survivors, rescuers and witness of terrorist attacks using structured interviews to assess the severity of posttraumatic stress, five months after the attacks. The study period extended from January 24, 2014 to March 24, 2014 which constitutes a total of period of 8 weeks. PTSD symptoms are measured using Posttraumatic Symptom Scale Interview (PSSI) and conferred to a diagnosis of PTSD at 5 months. Additionally, the severity of PTSD symptoms were determined using PSSI scores, severity ranged from 0-51. Of the one hundred survey respondents, 88% were males and 12% were females. Forty percent (40%) had attained 10 years of education, matriculation, but irrespective of the gender or educational status, all had some degree of PTSD. Sixty-six (66%) percent respondents are diagnosed as having moderate PTSD while 11% of the sample suffered from severe PTSD level. Age, gender, occupation and education level did not have any correlation with PTSD development. The contemporary findings indicate that any person who has witnessed or survived catastrophes of terrorist activities like bomb blast or being exposed to suicide attacks is at risk for developing PTSD, and there is necessity to deliver specialized post-disaster mental health facilities to the people having substantial levels of PTSD after calamities of such great intensity.


A reconfigurable NAND/NOR genetic logic gate.
Engineering genetic Boolean logic circuits is a major research theme of synthetic biology. By altering or introducing connections between genetic components, novel regulatory networks are built in order to mimic the behaviour of electronic devices such as logic gates. While electronics is a highly standardized science, genetic logic is still in its infancy, with few agreed standards. In this paper we focus on the interpretation of logical values in terms of molecular concentrations. We describe the results of computational investigations of a novel circuit that is able to trigger specific differential responses depending on the input standard used. The circuit can therefore be dynamically reconfigured (without modification) to serve as both a NAND/NOR logic gate. This multi-functional behaviour is achieved by a) varying the meanings of inputs, and b) using branch predictions (as in computer science) to display a constrained output. A thorough computational study is performed, which provides valuable insights for the future laboratory validation. The simulations focus on both single-cell and population behaviours. The latter give particular insights into the spatial behaviour of our engineered cells on a surface with a non-homogeneous distribution of inputs. We present a dynamically-reconfigurable NAND/NOR genetic logic circuit that can be switched between modes of operation via a simple shift in input signal concentration. The circuit addresses important issues in genetic logic that will have significance for more complex synthetic biology applications.


Subependymal giant cell astrocytoma-like astrocytoma: a neoplasm with a distinct phenotype and frequent neurofibromatosis type-1-association.
Neurofibromatosis type-1 is a familial genetic syndrome associated with a predisposition to develop peripheral and central nervous system neoplasms. We have previously reported on a subset of gliomas developing in these patients with morphologic features resembling subependymal giant cell astrocytoma, but the molecular features of these tumors remain undefined. A total of 14 tumors were studied and all available slides were reviewed. Immunohistochemical stains and telomere-specific FISH were performed on all cases. In addition, next-generation sequencing was performed on 11 cases using a platform targeting 644 cancer-related genes. The average age at diagnosis was 28 years (range: 4-60, 9F/5M). All tumors involved the supratentorial compartment. Tumors were predominantly low grade (n = 12), with two high-grade tumors, and displayed consistent expression of glial markers. Next-generation sequencing demonstrated inactivating NF1 mutations in 10 (of 11) cases. Concurrent TSC2 and RPTOR mutations were present in two cases (1 sporadic and 1 neurofibromatosis type-1-associated). Interestingly, alternative lengthening of telomeres was present in 4 (of 14) (29%) cases. However, an ATRX mutation associated with aberrant nuclear ATRX expression was identified in only one (of four) cases with alternative lenghtening of telomeres. Gene variants in the DNA helicase RECQL4 (n = 2) and components of the Fanconi anemia complementation group (FANCD2, FANCF, FANCG) (n = 1) were identified in two alternative lenghtening of telomere-positive/ATRX-intact cases. Other variants involved genes related to NOTCH signaling, DNA maintenance/repair pathways, and epigenetic modulators. There were no mutations identified in DAXX, PTEN, PIK3C genes, TP53, H3F3A, HIST1H3B, or in canonical hotspots of IDH1, IDH2, or BRAF. A subset of subependymal giant cell astrocytoma-like astrocytomas are alternative lenghtening of telomere-positive and occur in the absence of ATRX alterations, thereby suggesting mutations in other DNA repair/maintenance genes may also facilitate alternative lenghtening of telomeres. These findings suggest that subependymal giant cell astrocytoma-like astrocytoma represents a biologically distinct group that merits further investigation.


The LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity.
The forkhead transcription factor FoxO1 has been identified as a negative regulator of insulin/IGF-1 signaling. Its function is inhibited by phosphorylation and nuclear exclusion through a PI3K-dependent pathway. However, the structure/function relationship of FoxO1 has not been elucidated completely. In this study, we carried out mutation analysis of the FoxO1 coactivator-interacting LXXLL motif (amino acids 459-463). Expression of a 3A/LXXAA mutant, in which 3 Akt phosphorylation sites (T24, S253, and S316) and 2 leucine residues in the LXXLL motif (L462 and L463) were replaced by alanine, decreased both Igfbp-1 and G6Pase promoter activity and endogenous Igfbp-1 and G6Pase gene expression in simian virus 40-transformed (SV40-transformed) hepatocytes. Importantly, mutagenesis of the LXXLL motif eliminated FoxO1 interaction with the nicotinamide adenine dinucleotide-dependent (NAD-dependent) deacetylase sirtuin 1 (Sirt1), sustained the acetylated state of FoxO1, and made FoxO1 nicotinamide and resveratrol insensitive, supporting a role for this motif in Sirt1 binding. Furthermore, intravenous administration of adenovirus encoding 3A/LXXAA FoxO1 into Lepr db/db mice decreased fasting blood glucose levels and improved glucose tolerance and was accompanied by reduced G6Pase and Igfbp-1 gene expression and increased hepatic glycogen content. In conclusion, the LXXLL motif of FoxO1 may have an important role for its transcriptional activity and Sirt1 binding and should be a target site for regulation of gene expression of FoxO1 target genes and glucose metabolism in vivo.


Brain Connectomics' Modification to Clarify Motor and Nonmotor Features of Myotonic Dystrophy Type 1.
The adult form of myotonic dystrophy type 1 (DM1) presents with paradoxical inconsistencies between severity of brain damage, relative preservation of cognition, and failure in everyday life. This study, based on the assessment of brain connectivity and mechanisms of plasticity, aimed at reconciling these conflicting issues. Resting-state functional MRI and graph theoretical methods of analysis were used to assess brain topological features in a large cohort of patients with DM1. Patients, compared to controls, revealed reduced connectivity in a large frontoparietal network that correlated with their isolated impairment in visuospatial reasoning. Despite a global preservation of the topological properties, peculiar patterns of frontal disconnection and increased parietal-cerebellar connectivity were also identified in patients' brains. The balance between loss of connectivity and compensatory mechanisms in different brain networks might explain the paradoxical mismatch between structural brain damage and minimal cognitive deficits observed in these patients. This study provides a comprehensive assessment of brain abnormalities that fit well with both motor and nonmotor clinical features experienced by patients in their everyday life. The current findings suggest that measures of functional connectivity may offer the possibility of characterizing individual patients with the potential to become a clinical tool.


The perforasome theory: vascular anatomy and clinical implications.
A clear understanding of the vascular anatomy of an individual perforator relative to its vascular territory and flow characteristics is essential for both flap design and harvest. The authors investigated the three-dimensional and four-dimensional arterial vascular territory of a single perforator, termed a "perforasome," in major clinically relevant areas of the body. A vascular anatomy study was performed using 40 fresh cadavers. A total of 217 flaps and arterial perforasomes were studied. Dissection of all perforators was performed under loupe magnification. Perforator flaps on the anterior trunk, posterior trunk, and extremities were studied. Flaps underwent both static (three-dimensional) and dynamic (four-dimensional) computed tomographic angiography to better assess vascular anatomy, flow characteristics, and the contribution of both the subdermal plexus and fascia to flap perfusion. The perfusion and vascular territory of perforators is highly complex and variable. Each perforasome is linked with adjacent perforasomes by means of two main mechanisms that include both direct and indirect linking vessels. Vascular axis follows the axiality of linking vessels. Mass vascularity of a perforator found adjacent to an articulation is directed away from that same articulation, whereas perforators found at a midpoint between two articulations, or midpoint in the trunk, have a multidirectional flow distribution. Each perforator holds a unique vascular territory (perforasome). Perforator vascular supply is highly complex and follows some common guidelines. Direct and indirect linking vessels play a critical part in perforator flap perfusion, and every clinically significant perforator has the potential to become either a pedicle or free perforator flap.


Virtual Environmental Enrichment through Video Games Improves Hippocampal-Associated Memory.
The positive effects of environmental enrichment and their neural bases have been studied extensively in the rodent (van Praag et al., 2000). For example, simply modifying an animal's living environment to promote sensory stimulation can lead to (but is not limited to) enhancements in hippocampal cognition and neuroplasticity and can alleviate hippocampal cognitive deficits associated with neurodegenerative diseases and aging. We are interested in whether these manipulations that successfully enhance cognition (or mitigate cognitive decline) have similar influences on humans. Although there are many "enriching" aspects to daily life, we are constantly adapting to new experiences and situations within our own environment on a daily basis. Here, we hypothesize that the exploration of the vast and visually stimulating virtual environments within video games is a human correlate of environmental enrichment. We show that video gamers who specifically favor complex 3D video games performed better on a demanding recognition memory task that assesses participants' ability to discriminate highly similar lure items from repeated items. In addition, after 2 weeks of training on the 3D video game Super Mario 3D World, naive video gamers showed improved mnemonic discrimination ability and improvements on a virtual water maze task. Two control conditions (passive and training in a 2D game, Angry Birds), showed no such improvements. Furthermore, individual performance in both hippocampal-associated behaviors correlated with performance in Super Mario but not Angry Birds, suggesting that how individuals explored the virtual environment may influence hippocampal behavior. The hippocampus has long been associated with episodic memory and is commonly thought to rely on neuroplasticity to adapt to the ever-changing environment. In animals, it is well understood that exposing animals to a more stimulating environment, known as environmental enrichment, can stimulate neuroplasticity and improve hippocampal function and performance on hippocampally mediated memory tasks. Here, we suggest that the exploration of vast and visually stimulating environments within modern-day video games can act as a human correlate of environmental enrichment. Training naive video gamers in a rich 3D, but not 2D, video game, resulted in a significant improvement in hippocampus-associated cognition using several behavioral measures. Our results suggest that modern day video games may provide meaningful stimulation to the human hippocampus.


How can rAAV-α-synuclein and the fibril α-synuclein models advance our understanding of Parkinson's disease?
Animal models of Parkinson's disease (PD) are important for understanding the mechanisms of the disease and can contribute to developing and validating novel therapeutics. Ideally, these models should replicate the cardinal features of PD, such as progressive neurodegeneration of catecholaminergic neurons and motor defects. Many current PD models emphasize pathological forms of α-synuclein, based on findings that autosomal dominant mutations in α-synuclein and duplications/triplications of the SNCA gene cause PD. In addition, Lewy bodies and Lewy neurites, primarily composed of α-synuclein, represent the predominant pathological characteristics of PD. These inclusions have defined features, such as insolubility in non-ionic detergent, hyperphosphorylation, proteinase K sensitivity, a filamentous appearance by electron microscopy, and β-sheet structure. Furthermore, it has become clear that Lewy bodies and Lewy neurites are found throughout the peripheral and central nervous system, and could account not only for motor symptoms, but also for non-motor symptoms of the disease. The goal of this review is to describe two new α-synuclein-based models: the recombinant adeno-associated viral vector-α-synuclein model and the α-synuclein fibril model. An advantage of both models is that they do not require extensive crossbreeding of rodents transgenic for α-synuclein with other rodents transgenic for genes of interest to study the impact of such genes on PD-related pathology and phenotypes. In addition, abnormal α-synuclein can be expressed in brain regions relevant for disease. Here, we discuss the features of each model, how each model has contributed thus far to our understanding of PD, and the advantages and potential caveats of each model. This review describes two α-synuclein-based rodent models of Parkinson's disease: the rAAV-α-synuclein model and the α-synuclein fibril model. The key features of these models are described, and the extent to which they recapitulate features of PD, such as α-synuclein inclusion formation, loss of dopaminergic synapses in the striatum, motor defects, inflammation, and dopamine neuron death. This article is part of a special issue on Parkinson disease.


The ST segment of the ambulatory electrocardiogram in a normal population.
The behaviour of the ST segment in everyday life was studied by ambulatory electrocardiography in 111 normal volunteers. Fifteen were excluded because of abnormal exercise responses (10 subjects) and significant postural ST segment shifts (five subjects). This left 62 men and 34 women, mean (SD) age 40.5 (12.6) years (range 20-67 years). Ambulatory monitoring of leads CM5 and CC5 for 24 hours was followed by a maximal treadmill exercise test. The tapes of the ambulatory monitoring were analysed by a computer aided system. The computer printed trend plots of the ST segment (measured both at the J point and at J + 60 ms) to detect episodes of ST segment elevation and depression, which were confirmed by visual analysis of real time printouts. Twelve subjects showed "ischaemic" ST segment depression and nine subjects showed ST segment elevation. Eight people with ambulatory ST segment changes were studied during exercise by radionuclide ventriculography and thallium-201 imaging scans. Although seven of the eight thallium studies were normal, radionuclide ventriculography showed functional impairment in five cases. Seven of the 10 subjects with abnormal exercise tests were similarly investigated and their results followed the same pattern, with normal thallium images in six and functional impairment in four. Ambulatory electrocardiography was repeated in 20 people after a median of 20 days. The ST segment changes were reproducible. ST segment changes of an apparently ischaemic nature occur even in a carefully defined normal population but they do not necessarily represent latent clinically significant coronary artery disease. This indicates that ST segment changes seen in patients with known obstructive coronary artery disease should be interpreted with caution.


A neurosurgeon's guide to stem cells, cancer stem cells, and brain tumor stem cells.
Stem cells and their potential applications have become the forefront of scientific, political, and ethical discourse. Whereas stem cells were long accepted as units of development and evolution, it is now becoming increasingly clear that they are also units of oncogenesis. Although the field of stem cell biology is expanding at an astounding rate, the data attained are not readily translatable for the physicians who may eventually deliver these tools to patients. Herein, we provide a brief review of stem cell and cancer stem cell biology and highlight the scientific and clinical implications of recent findings regarding the presence of cancer-forming stem cells in brain tumors.


COMP-Ang1 stimulates HIF-1α-mediated SDF-1 overexpression and recovers ischemic injury through BM-derived progenitor cell recruitment.
Recruitment and adhesion of bone marrow (BM)-derived circulating progenitor cells to ischemic tissue are important for vasculogenesis and tissue repair. Recently, we found cartilage oligomeric matrix protein (COMP)-Ang1 is a useful cell-priming agent to improve the therapeutic efficacy of progenitor cells. However, the effect and the underlying mechanisms of COMP-Ang1 on recruitment of BM-derived progenitor cells (BMPCs) to foci of vascular injury have not been well defined. Here, we found that COMP-Ang1 is a critical stimulator of stromal cell-derived factor 1 (SDF-1), the principal regulator of BM-cell trafficking. Furthermore, SDF-1 stimulation by COMP-Ang1 was blocked by small-interfering RNA (siRNA) against hypoxia-inducible factor-1α (HIF-1α). COMP-Ang1 increased the synthesis of HIF-1α by activating mammalian target of rapamycin (mTOR) in hypoxic endothelium. The intermediate mechanism transmitting the COMP-Ang1 signal to the downstream mTOR/HIF-1α/SDF-1 pathway was the enhanced binding of the Tie2 receptor with integrin-linked kinase (ILK), an upstream activator of mTOR. In the mouse ischemic model, local injection of COMP-Ang1 stimulated the incorporation of BMPCs into ischemic limb, thereby enhancing neovasculogenesis and limb salvage. Collectively, our findings identify the COMP-Ang1/HIF-1α/SDF-1 pathway as a novel inducer of BMPC recruitment and neovasculogenesis in ischemic disease.


An unusual alphasatellite associated with monopartite begomoviruses attenuates symptoms and reduces betasatellite accumulation.
The Oman strain of Tomato yellow leaf curl virus (TYLCV-OM) and its associated betasatellite, an isolate of Tomato leaf curl betasatellite (ToLCB), were previously reported from Oman. Here we report the isolation of a second, previously undescribed, begomovirus [Tomato leaf curl Oman virus (ToLCOMV)] and an alphasatellite from that same plant sample. This alphasatellite is closely related (90 % shared nucleotide identity) to an unusual DNA-2-type Ageratum yellow vein Singapore alphasatellite (AYVSGA), thus far identified only in Singapore. ToLCOMV was found to have a recombinant genome comprising sequences derived from two extant parents, TYLCV-OM, which is indigenous to Oman, and Papaya leaf curl virus from the Indian subcontinent. All possible combinations of ToLCOMV, TYLCV-OM, ToLCB and AYVSGA were used to agro-inoculate tomato and Nicotiana benthamiana. Infection with ToLCOMV yielded mild leaf-curl symptoms in both hosts; however, plants inoculated with TYLCV-OM developed more severe symptoms. Plants infected with ToLCB in the presence of either helper begomovirus resulted in more severe symptoms. Surprisingly, symptoms in N. benthamiana infected with the alphasatellite together with either of the helper viruses and the betasatellite were attenuated and betasatellite DNA accumulation was substantially reduced. However, in the latter plants no concomitant reduction in the accumulation of helper virus DNA was observed. This is the first example of an attenuation of begomovirus-betasatellite symptoms by this unusual class of alphasatellites. This observation suggests that some DNA-2 alphasatellites encode a pathogenicity determinant that may modulate begomovirus-betasatellite infection by reducing betasatellite DNA accumulation.


A randomized, double-blind, placebo-controlled trial to assess safety and tolerability during treatment of type 2 diabetes with usual diabetes therapy and either Cycloset or placebo.
Cycloset is a quick-release formulation of bromocriptine mesylate, a dopamine agonist, which in animal models of insulin resistance and type 2 diabetes acts centrally to reduce resistance to insulin- mediated suppression of hepatic glucose output and tissue glucose disposal. In such animals, bromocriptine also reduces hepatic triglyceride synthesis and free fatty acid mobilization, manifesting decreases in both plasma triglycerides and free fatty acids. In clinical trials, morning administration of Cycloset either as monotherapy or adjunctive therapy to sulfonylurea or insulin reduces HbA1c levels relative to placebo by 0.55-1.2. Cycloset therapy also reduces plasma triglycerides and free fatty acid by approximately 25% and 20%, respectively, among those also receiving sulfonylurea therapies. The effects of once-daily morning Cycloset therapy on glycemic control and plasma lipids are demonstrable throughout the diurnal portion of the day (7 a.m. to 7 p.m.) across postprandial time points. 3,095 individuals were randomized in a 2:1 ratio into a one year trial aimed to assess the safety and efficacy of Cycloset compared to placebo among individuals receiving a variety of treatments for type 2 diabetes. Eligibility criteria for this randomized placebo controlled trial included: age 30-80, HbA1c <or= 10%, diabetes therapeutic regimen consisting of diet or no more than two hypoglycemic agents or insulin with or without one additional oral agent (usual diabetes therapy; UDT). The primary safety endpoint will test the hypothesis that the rate of all-cause serious adverse events after one year of usual diabetes therapy (UDT) plus Cycloset is not greater than that for UDT plus placebo by more than an acceptable margin defined as a hazard ratio of 1.5 with a secondary endpoint analysis of the difference in the rate of serious cardiovascular events, (myocardial infarction, stroke, coronary revascularization or hospitalization for or angina or congestive heart failure). Efficacy analyses will evaluate effects of Cycloset versus placebo on change from baseline in HbA1c, fasting glucose, body weight, waist circumference, blood pressure and plasma lipids. This study will extend the current data on Cycloset safety, tolerability and efficacy in individuals with type 2 diabetes to include its effects in combination with thiazolodinediones, insulin secretagogues, metformin, alpha-glucosidase inhibitors and exogenous insulin regimens. clinical trials.gov NCT00377676.


"Turn-on" Pb2+ sensing and rapid detection of biothiols in aqueous medium and real samples.
Detection of lead has continued to be of immense interest in the present industrial as well as environmental diaspora. To this end, we report a prudent Schiff base which enables the sensitive detection of Pb2+ ions in mixed aqueous medium. The probe is afforded by simple synthetic and purification processes. Further, the probe employs simple mechanistic detection of Pb2+ and also successively detects a host of biothiols. The sensor is also used to detect Pb2+ ions in real water samples and consecutive detection of a variety of biothiols, including functionalized thiouracils, in onion and garlic extract. The fact that the Pb2+-L ensemble is 'non-selective' towards any particular thiol substituted analyte in real samples could as well prove to be an interesting contribution for chemical and biological detoxification processes.


Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein require an N-terminal trimerization domain.
Proteins of the echinoderm microtubule (MT)-associated protein (EMAP)-like (EML) family contribute to formation of the mitotic spindle and interphase MT network. EML1-4 consist of Trp-Asp 40 (WD40) repeats and an N-terminal region containing a putative coiled-coil. Recurrent gene rearrangements in non-small cell lung cancer (NSCLC) fuse EML4 to anaplastic lymphoma kinase (ALK) causing expression of several oncogenic fusion variants. The fusions have constitutive ALK activity due to self-association through the EML4 coiled-coil. We have determined crystal structures of the coiled-coils from EML2 and EML4, which describe the structural basis of both EML self-association and oncogenic EML4-ALK activation. The structures reveal a trimeric oligomerization state directed by a conserved pattern of hydrophobic residues and salt bridges. We show that the trimerization domain (TD) of EML1 is necessary and sufficient for self-association. The TD is also essential for MT binding; however, this property requires an adjacent basic region. These observations prompted us to investigate MT association of EML4-ALK and EML1-ABL1 (Abelson 1) fusions in which variable portions of the EML component are present. Uniquely, EML4-ALK variant 3, which includes the TD and basic region of EML4 but none of the WD40 repeats, was localized to MTs, both when expressed recombinantly and when expressed in a patient-derived NSCLC cell line (H2228). This raises the question of whether the mislocalization of ALK activity to MTs might influence downstream signalling and malignant properties of cells. Furthermore, the structure of EML4 TD may enable the development of protein-protein interaction inhibitors targeting the trimerization interface, providing a possible avenue towards therapeutic intervention in EML4-ALK NSCLC.


Comparison of Protein-Pacing Alone or With Yoga/Stretching and Resistance Training on Glycemia, Total and Regional Body Composition, and Aerobic Fitness in Overweight Women.
Yoga/Stretching (YS) and functional resistance (FR) training are popular exercise routines. A protein-pacing (PP) diet is a common dietary regimen. Thus, we assessed the effectiveness of a PP diet alone and in combination with either YS or FR to improve body composition and cardiometabolic health. Twenty-seven overweight women (age = 43.2 ± 4.6 years) were randomized into 3 groups: yoga (YS, n = 8) or resistance (FR, n = 10) training (3 days/week) in conjunction with PP diet (50% carbohydrate, 25% protein, and 25% fat) or PP diet-only (PP, n = 9) throughout 12-week study. PP maintained preexisting levels of physical activity. Body weight (BW), total (BF) and abdominal (ABF) body fat, waist circumference (WC), plasma biomarkers, and aerobic fitness (VO2) were measured at baseline and 12 weeks. WC and total cholesterol improved in all groups, whereas glycemia tended to improve (P = .06) in S. BF, ABF, and VO2 increased significantly in YS and FR (P < .05). Feelings of vigor increased in YS and tension decreased in FR (P < .05). YS training tended to decrease blood glucose compared with FR and PP and is equally effective at enhancing body composition, and aerobic fitness in overweight women providing a strong rationale for further research on YS training.


Inverse association between lipid levels and mortality in men with chronic kidney disease who are not yet on dialysis: effects of case mix and the malnutrition-inflammation-cachexia syndrome.
High total cholesterol is associated with lower mortality in dialysis patients, but the relationship between lipid levels and mortality in patients who have chronic kidney disease (CKD) and are not yet on dialysis is poorly described. This study examined the association between lipid levels and all-cause and cardiovascular mortality in 986 male patients (age 67.4 +/- 10.9 yr; race 23.7% black) who had CKD and were not yet on dialysis. Associations were determined in fixed-covariate and time-dependent Cox models, before and after adjustment for components of case mix and surrogates for malnutrition-inflammation-cachexia syndrome (MICS). Lower total cholesterol quartiles were associated with higher all-cause mortality in a fixed-covariate model that was adjusted for age, race, and body mass index (hazard ratio [95% confidence interval] for cholesterol <153, 153 to 182, and 183 to 215 versus >215 mg/dl: 1.91 [1.35 to 2.69], 1.36 [0.96 to 1.92], 1.10 [0.78 to 1.57]; P < 0.001 for trend), but this association was attenuated after adjustment for case mix (P = 0.023 for trend) and abolished after additional adjustment for MICS (P = 0.14 for trend), with time-dependent Cox models showing similar results. Similar tendencies also were detected in the association between levels of LDL cholesterol with total and cardiovascular mortality and triglycerides with all-cause mortality in both fixed-covariate and time-dependent analyses. Lower lipid levels are associated with higher mortality in patients who have moderate and advanced CKD and are not yet on dialysis. This inverse association is explained in part by case-mix characteristics and the presence of surrogates for MICS.


Intravenous high-dose interferon with or without maintenance treatment in melanoma at high risk of recurrence: meta-analysis of three trials.
Resected stage IIB-IIIC malignant melanoma has a poor prognosis with a high risk of relapse and death. Treatment with adjuvant interferon alfa-2b (IFN-α-2b) is associated with improved relapse-free and overall survivals (OS), but the most appropriate dose and duration of treatment are unknown. In this article, we present an individual patient data random effects meta-analysis of melanoma patients from the U.K., Greek, and Chinese randomized trials. All patients were randomized either to IFN-α-2b 15-20 MIU/m(2) IV daily 5 days per week for 4 weeks (IV) or to the same regimen followed by IFN-α-2b 9-10 MIU/m(2) administered three times per week for 48 weeks (IV and SC). Allowing for dose interruptions and reductions, an equivalent total dose of IFN-α-2b was delivered in all three studies. We assessed whether IV was noninferior to IV and SC in terms of relapse-free survival (RFS) and investigated tumor and patient characteristics that impacted on outcomes. Median follow-up of 716 stage IIB-IIIC patients was 5.4 years. Noninferiority of IV compared to IV and SC could not be conferred for RFS (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.89-1.52; noninferior P = 0.17). Stage (P < 0.0001), site (acral vs. other, P < 0.0001), and Breslow thickness (P = 0.02) were significant predictors of RFS. The HR for death was 1.13 for IV compared to IV and SC, (95% CI 0.91-1.39). Stage (P < 0.0001) and Breslow thickness (P = 0.001) were significant independent predictors of OS. The available data suggest that where adjuvant high-dose interferon is being considered there is no evidence to deviate from the year long regimen described in the Eastern Cooperative Oncology Group and Intergroup studies.


Cardiovascular risk factors among patients with chronic kidney disease attending a tertiary hospital in Uganda.
Chronic kidney disease (CKD) is a risk factor for the development of cardiovascular disease, which is the primary cause of morbidity and mortality in patients with CKD. Local data about cardiovascular risk factors among CKD patients is generally scanty. To determine the prevalence of the common cardiovascular risk factors among patients with CKD attending the nephrology out-patient clinic in Mulago national referral hospital in Uganda. This was a cross-sectional study in which 217 patients with a mean age of 43 years were recruited over a period of nine months. Data on demographic characteristics, risk factors for cardiovascular disease, complete blood count, renal function tests/electrolytes, and lipid profiles were collected using a standardised questionnaire. One hundred and eleven (51.2%) of the participants were male. Hypertension was reported in 90% of participants while cigarette smoking was present in 11.5%. Twenty-two participants (10.2%) were obese and 16.1% were diabetic. A total of 71.9% had a haemoglobin concentration < 11 g/dl, with the prevalence of anaemia increasing with advancing renal failure (p < 0.001); 44.7% were hypocalcaemic and 39.2% had hyperphosphataemia. The prevalence of abnormal calcium and phosphate levels was found to increase with declining renal function (p = 0.004 for calcium and p < 0.001 for phosphate). This study demonstrated that both traditional and non-traditional cardiovascular risk factors occurred frequently in patients with CKD attending the nephrology out-patient clinic at Mulago Hospital.


Neural emotion regulation circuitry underlying anxiolytic effects of perceived control over pain.
Anxiolytic effects of perceived control have been observed across species. In humans, neuroimaging studies have suggested that perceived control and cognitive reappraisal reduce negative affect through similar mechanisms. An important limitation of extant neuroimaging studies of perceived control in terms of directly testing this hypothesis, however, is the use of within-subject designs, which confound participants' affective response to controllable and uncontrollable stress. To compare neural and affective responses when participants were exposed to either uncontrollable or controllable stress, two groups of participants received an identical series of stressors (thermal pain stimuli). One group ("controllable") was led to believe they had behavioral control over the pain stimuli, whereas another ("uncontrollable") believed they had no control. Controllable pain was associated with decreased state anxiety, decreased activation in amygdala, and increased activation in nucleus accumbens. In participants who perceived control over the pain, reduced state anxiety was associated with increased functional connectivity between each of these regions and ventral lateral/ventral medial pFC. The location of pFC findings is consistent with regions found to be critical for the anxiolytic effects of perceived control in rodents. Furthermore, interactions observed between pFC and both amygdala and nucleus accumbens are remarkably similar to neural mechanisms of emotion regulation through reappraisal in humans. These results suggest that perceived control reduces negative affect through a general mechanism involved in the cognitive regulation of emotion.


Mid-life stress and cognitive deficits during early aging in rats: individual differences and hippocampal correlates.
We explored here the possibility that mid-life stress in rats could have deleterious effects on cognitive abilities during early aging, as well as the potential role of inter-individual differences on the development of such effects. Male Wistar rats were classified according to their reactivity to novelty (4 months old) as highly (HR) or low (LR) reactive and, at mid-life (12 months old), either submitted to chronic stress (28 days) or left undisturbed. At early aging (18 months old), their learning abilities were tested in the water maze, and a number of neuroendocrine (plasma corticosterone; hippocampal corticosteroid receptors) and neurobiological (hippocampal expression of neuronal cell adhesion molecules) parameters were evaluated. Impaired performance was observed in stressed HR rats, as compared to unstressed HR and stressed LR rats. Increased hippocampal mineralocorticoid receptors were found in stressed LR rats when compared with stressed HR and control LR groups. In addition, mid-life stress-induced an increased corticosterone response and a reduction in NCAM-180 isoform and L1 regardless of the behavioral trait of novelty reactivity. These findings highlight a role of stress experienced throughout life on cognitive impairment occurring during the early aging period, as well as the importance of taking into account individual differences to understand variability in such cognitive decline.


Serum gastrin in chronic gastritis.
Fasting gastrin levels in serum were measured in 49 patients with different types of chronic gastritis and in matched controls. In 15 patients with established pernicious anaemia the mean (+/- S.E. of mean) level of gastrin was greatly raised (699 +/- 99 pg/ml). In 17 patients with chronic atrophic gastritis, seropositive for parietal cell antibody but with adequate vitamin-B(12) absorption, the level was also raised (476 +/- 74 pg/ml). By contrast, in "simple" atrophic gastritis seronegative for parietal cell antibody the gastrin levels were significantly lower for both diffuse atrophic gastritis (129 +/- 31 pg/ml) and multifocal gastritis (14 +/- 4 pg/ml). These levels were similar to those in the controls (46 +/- 7 pg/ml).The mechanism of the raised gastrin levels remains uncertain, but neither achlorhydria nor in vivo action of the parietal cell antibody wholly accounted for the hypergastrinaemia.We conclude that hypergastrinaemia is characteristic of gastritis associated with autoimmune reactions to gastric antigens and pernicious anaemia and that a raised serum gastrin is a useful marker of the type of gastritis that tends to progress to the gastric lesion of pernicious anaemia. The findings suggest that this type of gastritis is an essentially different disease from "simple" atrophic gastritis, and the differences in gastrin levels may be due to sparing of the antral mucosa in the autoimmune type but not in "simple" gastritis.


Updates in Gastrointestinal Oncology - insights from the 2008 44th annual meeting of the American Society of Clinical Oncology.
We have reviewed the pivotal presentations rcelated to colorectal cancer (CRC) and other gastrointestinal malignancies from 2008 annual meeting of the American Society of Clinical Oncology (ASCO). We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. The report on KRAS status in patients with metastatic CRC receiving epidermal growth factor receptor (EGFR) targeted antibody treatment has led to a change in National Comprehensive Cancer Network guideline that recommends only patients with wild-type KRAS tumor should receive this treatment. The results of double biologics (bevacizumab and anti-EGFR antibody) plus chemotherapy as first-line treatment in patients with metastatic CRC has shown a worse outcome than bevacizumab-based regimen. Microsatellite Instability has again been confirmed to be an important predictor in patients with stage II colon cancer receiving adjuvant treatment. Adjuvant gemcitabine therapy for pancreatic cancer was investigated by the CONKO-001 study; this resulted in superior survival as compared with observation and can be regarded as an acceptable option, without the addition of radiotherapy. The addition of bevacizumab to gemcitabine and erlotinib was not supior to gemcitabine and erlotinib for advanced disease. Second-line therapy for advanced pancreatic cancer with 5-fluorouracil and oxaliplatin resulted in a survival benefit. Irinotecan plus cisplatin and paclitaxel plus cisplatin result in similar survival when combined with radiotherapy for esophageal cancer. The novel fluoropyrimidine S1 appears to be active in gastric cancer, as a single agent or as combination therapy. Adjuvant intraperitoneal mitomycin-C may decrease the incidence of peritoneal recurrence of gastric cancer. Sorafenib is an effective agent in Asian patients with hepatocellular carcinoma secondary to hepatitis B; its utility in child's B cirrhosis remains to be proven. Sunitinib is also an active agent in hepatocellular carcinoma, and may represent an alterative to sorafenib for advanced disease. These and other important presentations from the 2008 ASCO annual meeting are discussed in this article.


Mammalian DNA polymerase auxiliary proteins: analysis of replication factor C-catalyzed proliferating cell nuclear antigen loading onto circular double-stranded DNA.
To understand the mechanism of action of the two eukaryotic replication auxiliary proteins proliferating cell nuclear antigen (PCNA) and replication factor C (RF-C), we constructed a plasmid for producing PCNA which could be 32P labelled in vitro. This allowed us to analyze the assembly of the auxiliary proteins directly on DNA and to examine this process in the absence of DNA synthesis. By using closed circular double-stranded DNA or gapped circular DNA for protein-DNA complex formation, the following results were obtained, (i) RF-C can load PCNA in an ATP-dependent manner directly on double-stranded DNA, and no 3'-OH ends are required for this reaction; (ii) the RF-C-PCNA complex assembled on closed circular DNA differs from those assembled on gapped or nicked circular DNA; (iii) the stable RF-C-PCNA complex can be assembled on circular but not on linear DNA; and (iv) only gapped DNA can partially retain the assembled RF-C-PCNA complex upon the linearization of the template. We propose that RF-C first binds unspecifically to double-stranded DNA in the presence of ATP and then loads PCNA onto DNA to yield a protein complex able to track along DNA. The RF-C-PCNA complex could slide along the template until it encounters a 3'-OH primer-template junction, where it is likely transformed into a competent clamp. The latter complex, finally, might still be able to slide along double-stranded DNA.


Broadly Conserved Fungal Effector BEC1019 Suppresses Host Cell Death and Enhances Pathogen Virulence in Powdery Mildew of Barley (Hordeum vulgare L.).
The interaction of barley, Hordeum vulgare L., with the powdery mildew fungus Blumeria graminis f. sp. hordei is a well-developed model to investigate resistance and susceptibility to obligate biotrophic pathogens. The 130-Mb Blumeria genome encodes approximately 540 predicted effectors that are hypothesized to suppress or induce host processes to promote colonization. Blumeria effector candidate (BEC)1019, a single-copy gene encoding a putative, secreted metalloprotease, is expressed in haustorial feeding structures, and host-induced gene silencing of BEC1019 restricts haustorial development in compatible interactions. Here, we show that Barley stripe mosaic virus-induced gene silencing of BEC1019 significantly reduces fungal colonization of barley epidermal cells, demonstrating that BEC1019 plays a central role in virulence. In addition, delivery of BEC1019 to the host cytoplasm via Xanthomonas type III secretion suppresses cultivar nonspecific hypersensitive reaction (HR) induced by Xanthomonas oryzae pv. oryzicola, as well as cultivar-specific HR induced by AvrPphB from Pseudomonas syringae pv. phaseolicola. BEC1019 homologs are present in 96 of 241 sequenced fungal genomes, including plant pathogens, human pathogens, and free-living nonpathogens. Comparative analysis revealed variation at several amino acid positions that correlate with fungal lifestyle and several highly conserved, noncorrelated motifs. Site-directed mutagenesis of one of these, ETVIC, compromises the HR-suppressing activity of BEC1019. We postulate that BEC1019 represents an ancient, broadly important fungal protein family, members of which have evolved to function as effectors in plant and animal hosts.


Liver disease in chelated transfusion-dependent thalassemics: the role of iron overload and chronic hepatitis C.
Iron overload and hepatitis virus C infection cause liver fibrosis in thalassemics. In a monocentric retrospective analysis of liver disease in a cohort of 191 transfusion-dependent thalassemics, in 126 patients who had undergone liver biopsy (mean age 17.2 years; 58 hepatitis virus C-RNA positive and 68 hepatitis virus C-RNA negative) the liver iron concentration (median 2.4 mg/gr dry liver weight) was closely related to serum ferritin levels (R = 0.58; p<0.0001). Male gender (OR 4.12) and serum hepatitis virus C-RNA positivity (OR 11.04) were independent risk factors for advanced liver fibrosis. The majority of hepatitis virus C-RNA negative patients with low iron load did not develop liver fibrosis, while hepatitis virus C-RNA positive patients infected with genotype 1 or 4 and iron overload more frequently developed advanced fibrosis. Hepatitis virus C infection is the main risk factor for liver fibrosis in transfusion-dependent thalassemics. Adequate chelation therapy usually prevents the development of liver fibrosis in thalassemics free of hepatitis virus C-infection and reduces the risk of developing severe fibrosis in thalassemics with chronic hepatitis C.


Novel cannabidiol sunscreen protects keratinocytes and melanocytes against ultraviolet B radiation.
Cannabidiol (CBD), a natural occurring phytocannabinoid, is used extensively in consumer products ranging from foods to shampoos, topical oils and lotions. Several studies demonstrated the anti-inflammatory and antioxidative properties of cannabidiol. Nevertheless, the role of cannabidiol use in sunscreens is largely unknown as no studies on its effect on keratinocytes or melanocytes exist. As such, we aimed to explore the effect of CBD on keratinocyte and melanocyte viability following ultraviolet B (UVB) irradiation. CBD exhibited a dose-dependent protective effect on both keratinocytes and melanocyte viability. Further, since CBD does not demonstrate absorption in the UVB spectra, we speculate that the protective effect is due to reduction in reactive oxygen species. To our knowledge, this is the first study demonstrating the protective effect of CBD on keratinocytes and melanocytes irradiated with UVB.


Single-dose hydrocortisone administration does not enhance motor sequence learning or reward learning in humans.
Despite its physiological and clinical relevance, the influence of hydrocortisone on specific kinds of learning remains relatively unexplored. We measured the effect of hydrocortisone on motor sequence and reward learning under non-stress conditions. For the study, 54 healthy young volunteers were randomly assigned to a dose of 20 mg hydrocortisone versus placebo. Participants performed two well-defined learning tasks. Hydrocortisone did not affect motor sequence or reward learning.


Controlling the duty cycle of the eigenstates in laser with multiple optical feedback.
The polarization dynamics of a quasi-isotropic single-mode laser subjected to multiple optical feedback is presented. The variable duty cycle of two eigenstates is observed in high-frequency optical fringes. The high-frequency optical fringes are induced by the multiple reflections in the asymmetry feedback cavity. The duty cycle of two eigenstates can be controlled easily by adjusting the position of polarization flipping due to the residual stress of laser mirror. Particularly, when the frequency difference results from residual stress is reduced to 1.5MHz, the position of polarization flipping moves to the edge of each fringe which can be used to measure small displacement with direction sensitivity and high resolution.


Energy intake, meal frequency, and health: a neurobiological perspective.
The size and frequency of meals are fundamental aspects of nutrition that can have profound effects on the health and longevity of laboratory animals. In humans, excessive energy intake is associated with increased incidence of cardiovascular disease, diabetes, and certain cancers and is a major cause of disability and death in industrialized countries. On the other hand, the influence of meal frequency on human health and longevity is unclear. Both caloric (energy) restriction (CR) and reduced meal frequency/intermittent fasting can suppress the development of various diseases and can increase life span in rodents by mechanisms involving reduced oxidative damage and increased stress resistance. Many of the beneficial effects of CR and fasting appear to be mediated by the nervous system. For example, intermittent fasting results in increased production of brain-derived neurotrophic factor (BDNF), which increases the resistance of neurons in the brain to dysfunction and degeneration in animal models of neurodegenerative disorders; BDNF signaling may also mediate beneficial effects of intermittent fasting on glucose regulation and cardiovascular function. A better understanding of the neurobiological mechanisms by which meal size and frequency affect human health may lead to novel approaches for disease prevention and treatment.


The immature endothelial cell in new vessel formation following surgical injury in rat brain.
We investigated neovasculatization in the cerebral cortex of the adult rat after surgical brain injury by ultrastructural, immunocytochemical and immunochemical means. Previously we described endothelial-like cell that participates in new vessel formation on plasma proteins that served as a provisional matrix in the region immediately adjacent to the traumatic injury. In the present study we describe new vessel formation in the multistep process with the alterations in endothelial-like cell immunophenotype. The observations were conducted from 2 to 7 days after induction of cortical trauma. Traumatic injury was induced in the frontotemporal region of cerebral cortex. We show that endothelial-like cell could not successfully terminate its development without the presence of pericyte and astrocyte. New formed blood vessels were accompanied by fibroblast and lipofibroblast cells differentiated probably from common progenitor. Our result suggests that endothelial-like cell is committed endothelial cell between progenitor endothelial cell and terminally differentiated endothelium stage. Therefore, we propose that our of endothelial stem cells present in blood at different stages of morphogenetic differentiation and specifically arrested in "check points" of development trauma mobilize the group of the most differentiated progenitors. These may contribute to new vessel formation. Our model should be useful for the characterization of endothelial commitment and endothelial cell differentiation after brain injury.


A One Health Evaluation of the Southern African Centre for Infectious Disease Surveillance.
Rooted in the recognition that emerging infectious diseases occur at the interface of human, animal, and ecosystem health, the Southern African Centre for Infectious Disease Surveillance (SACIDS) initiative aims to promote a trans-sectoral approach to address better infectious disease risk management in five countries of the Southern African Development Community. Nine years after SACIDS' inception, this study aimed to evaluate the program by applying a One Health (OH) evaluation framework developed by the Network for Evaluation of One Health (NEOH). The evaluation included a description of the context and the initiative, illustration of the theory of change, identification of outputs and outcomes, and assessment of the One Healthness. The latter is the sum of characteristics that defines an integrated approach and includes OH thinking, OH planning, OH working, sharing infrastructure, learning infrastructure, and systemic organization. The protocols made available by NEOH were used to develop data collection protocols and identify the study design. The framework relies on a mixed methods approach by combining a descriptive and qualitative assessment with a semi-quantitative evaluation (scoring). Data for the analysis were gathered during a document review, in group and individual interviews and in an online survey. Operational aspects (i.e., OH thinking, planning, and working) were found to be balanced overall with the highest score in the planning dimension, whereas the infrastructure (learning infrastructure, systemic organization, and sharing infrastructure) was high for the first two dimensions, but low for sharing. The OH index calculated was 0.359, and the OH ratio calculated was 1.495. The program was praised for its great innovative energy in a difficult landscape dominated by poor infrastructure and its ability to create awareness for OH and enthuse people for the concept; training of people and networking. Shortcomings were identified regarding the balance of contributions, funds and activities across member countries in the South, lack of data sharing, unequal allocation of resources, top-down management structures, and limited horizontal collaboration. Despite these challenges, SACIDS is perceived to be an effective agent in tackling infectious diseases in an integrated manner.


Microfluidic bead-based diodes with targeted circular microchannels for low Reynolds number applications.
Self-regulating fluidic components are critical to the advancement of microfluidic processors for chemical and biological applications, such as sample preparation on chip, point-of-care molecular diagnostics, and implantable drug delivery devices. Although researchers have developed a wide range of components to enable flow rectification in fluidic systems, engineering microfluidic diodes that function at the low Reynolds number (Re) flows and smaller scales of emerging micro/nanofluidic platforms has remained a considerable challenge. Recently, researchers have demonstrated microfluidic diodes that utilize high numbers of suspended microbeads as dynamic resistive elements; however, using spherical particles to block fluid flow through rectangular microchannels is inherently limited. To overcome this issue, here we present a single-layer microfluidic bead-based diode (18 μm in height) that uses a targeted circular-shaped microchannel for the docking of a single microbead (15 μm in diameter) to rectify fluid flow under low Re conditions. Three-dimensional simulations and experimental results revealed that adjusting the docking channel geometry and size to better match the suspended microbead greatly increased the diodicity (Di) performance. Arraying multiple bead-based diodes in parallel was found to adversely affect system efficacy, while arraying multiple diodes in series was observed to enhance device performance. In particular, systems consisting of four microfluidic bead-based diodes with targeted circular-shaped docking channels in series revealed average Di's ranging from 2.72 ± 0.41 to 10.21 ± 1.53 corresponding to Re varying from 0.1 to 0.6.


A characterization of internet dating network structures among nordic men who have sex with men.
The Internet has become an important venue for seeking sexual partners and may facilitate transmission of sexually transmitted infections. We examined a 64-day data log of flirt messages expressing sexual interest among MSM within the Qruiser.com community. We used logistic regression to analyze characteristics of MSM sending and receiving flirt messages and negative binomial regression to examine individual activity and popularity. The structural properties, including the core structure of the flirt network, were analyzed. The MSM population consisted of approximately 40% homosexuals and 37% bisexuals, while the remaining 23% included men who identified as heterosexual but searched for sex with men and "experimental". MSM were more likely to send flirt messages if they were homosexual and aged 40+ years; young people aged < 30 years were more likely to receive a flirt. Possession of a webcam was strongly associated with both sending flirt messages and being a flirt target. The distributions of flirts sent (max k(out) = 2162) and received (max k(in) = 84) were highly heterogeneous. Members in central cores were more likely homosexuals, singles, and aged 31-40 years. The probability of a matched flirt (flirt returned from target) increased from 1% in the outer core to 18% in the central core (core size = 4). The flirt network showed high degree heterogeneity similar to the structural properties of real sexual contact networks with a single central core. Further studies are needed to explore use of webcam for Internet dating.


mTORC1 activation in podocytes is a critical step in the development of diabetic nephropathy in mice.
Diabetic nephropathy (DN) is among the most lethal complications that occur in type 1 and type 2 diabetics. Podocyte dysfunction is postulated to be a critical event associated with proteinuria and glomerulosclerosis in glomerular diseases including DN. However, molecular mechanisms of podocyte dysfunction in the development of DN are not well understood. Here we have shown that activity of mTOR complex 1 (mTORC1), a kinase that senses nutrient availability, was enhanced in the podocytes of diabetic animals. Further, podocyte-specific mTORC1 activation induced by ablation of an upstream negative regulator (PcKOTsc1) recapitulated many DN features, including podocyte loss, glomerular basement membrane thickening, mesangial expansion, and proteinuria in nondiabetic young and adult mice. Abnormal mTORC1 activation caused mislocalization of slit diaphragm proteins and induced an epithelial-mesenchymal transition-like phenotypic switch with enhanced ER stress in podocytes. Conversely, reduction of ER stress with a chemical chaperone significantly protected against both the podocyte phenotypic switch and podocyte loss in PcKOTsc1 mice. Finally, genetic reduction of podocyte-specific mTORC1 in diabetic animals suppressed the development of DN. These results indicate that mTORC1 activation in podocytes is a critical event in inducing DN and suggest that reduction of podocyte mTORC1 activity is a potential therapeutic strategy to prevent DN.


Physician practices related to use of BMI-for-age and counseling for childhood obesity prevention: a cross-sectional study.
Screening for obesity and providing appropriate obesity-related counseling in the clinical setting are important strategies to prevent and control childhood obesity. The purpose of this study is to document pediatricians (PEDs) and general practitioners (GPs) with pediatric patients use of BMI-for-age to screen for obesity, confidence in explaining BMI, access to referral clinics, and characteristics associated with screening and counseling to children and their caregivers. The authors used 2008 DocStyles survey data to examine these practices at every well child visit for children aged two years and older. Counseling topics included: physical activity, TV viewing time, energy dense foods, fruits and vegetables, and sugar-sweetened beverages. Chi-square tests were used to examine differences in proportions and logistic regression to identify characteristics associated with screening and counseling. The final analytic sample included 250 PEDs and 621 GPs. Prevalence of using BMI-for-age to screen for obesity at every well child visit was higher for PEDs than GPs (50% vs. 22%, χ2 = 67.0, p ≤ 0.01); more PEDs reported being very/somewhat confident in explaining BMI (94% vs. GPs, 87%, p < 0.01); more PEDs reported access to a pediatric obesity specialty clinic for referral (PEDs = 65% vs. GPs = 42%, χ2 = 37.5, p ≤ 0.0001).In general, PEDs reported higher counseling prevalence than GPs. There were significant differences in the following topics: TV viewing (PEDs, 79% vs. GPs, 61%, χ2 = 19.1, p ≤ 0.0001); fruit and vegetable consumption (PEDs, 87% vs. GPs, 78%, χ2 = 6.4, p ≤ 0.01). The only characteristics associated with use of BMI for GPs were being female (OR = 2.3, 95% CI = 1.5-3.5) and serving mostly non-white patients (OR = 1.8, 95% CI = 1.1-2.9); there were no significant associations for PEDs. The findings for use of BMI-for-age, counseling habits, and access to a pediatric obesity specialty clinic leave room for improvement. More research is needed to better understand why BMI-for-age is not being used to screen at every well child visit, which may increase the likelihood overweight and obese patients receive counseling and referrals for additional services. The authors also suggest more communication between PEDs and GPs through professional organizations to increase awareness of existing resources, and to enhance access and referral to pediatric obesity specialty clinics.


Jumping to conclusions and persecutory delusions.
It is unknown whether a 'jumping to conclusions' (JTC) data-gathering bias is apparent in specific delusion sub-types. A group with persecutory delusions is compared with a sample of non-clinical controls on a probabilistic reasoning task. Results suggest JTC is apparent in individuals with the persecutory sub-type of delusions.


Laparoscopic wedge resection of a midsized gastrointestinal stromal tumor near the esophagogastric junction.
Gastrointestinal stromal tumors are rare neoplasms involving the entire digestive system, in particular the stomach. Generally, laparoscopic wedge resection is the preferred means of treating anterior lesions, while the preferred means of treating tumors in the posterior wall and near the esophagogastric junction remains controversial. We report the case of a patient with a gastric stromal tumor in the posterior wall of the greater curvature approximately 3 cm from the esophagogastric junction. Under intraoperative ultrasonic guidance, a large wedge resection was done using an ultrasonic scalpel; the gastric wall was reconstructed through a long intracorporeal suture. At 6-month follow-up, the patient was free from tumor recurrence. If a meticulous surgical technique is followed, laparoscopic wedge resection is a safe and feasible means of treating gastric stromal tumors in the posterior wall near the esophagogastric junction.


Near-field optical experiments on low-symmetry split-ring-resonator arrays.
Effective symmetric and antisymmetric eigenmodes of coupled plasmonic resonances play a crucial role in many photonic metamaterials. Recently, we discussed a particular arrangement of metallic split-ring resonators that is planar, hence enabling direct experimental access to the different eigenmodes via near-field optical microscopy. In this Letter, corresponding optical experiments are presented and compared with simple theoretical modeling, providing a direct confirmation of our previous, more indirect conclusions.


Upconversion luminescence with tunable lifetime in NaYF4:Yb,Er nanocrystals: role of nanocrystal size.
Despite recent achievements to reduce surface quenching in NaYF(4):Yb,Er nanocrystals, a complete understanding of how the nanocrystal size affects the brightness of upconversion luminescence is still incomplete. Here we investigated upconversion luminescence of Yb,Er-doped nanocrystals in a broad range of sizes from 6 nm to 45 nm (cubic or hexagonal phases), displaying an increasing red-to-green luminescence intensity ratio and reduced luminescence lifetimes with decreasing size. By analyzing the upconversion process with a set of rate equations, we found that their asymptotic analytic solutions explain lower decay rates of red compared to green upconversion luminescence. Furthermore, we quantified the effect of the surface on luminescence lifetime in a model where nanocrystal emitters are divided between the near-surface and inside regions of each nanocrystal. We clarify the influence of the four nonradiative recombination mechanisms (intrinsic phonon modes, vibration energy of surface ligands, solvent-mediated quenching, and surface defects) on the decay rates for different-size nanocrystals, and find that the defect density dominates decay rates for small (below 15 nm) nanocrystals. Our results indicate that a defect-reduction strategy is a key step in producing small upconversion nanocrystals with increased brightness for a variety of bioimaging and biosensing applications.


The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions.
A rapid flow synthesis of oxazolines and their oxidation to the corresponding oxazoles is reported. The oxazolines are prepared at room temperature in a stereospecific manner, with inversion of stereochemistry, from β-hydroxy amides using Deoxo-Fluor®. The corresponding oxazoles can then be obtained via a packed reactor containing commercial manganese dioxide.


Discrepancies between Judgment and Choice of Action in Moral Dilemmas.
Everyone has experienced the potential discrepancy between what one judges as morally acceptable and what one actually does when a choice between alternative behaviors is to be made. The present study explores empirically whether judgment and choice of action differ when people make decisions on dilemmas involving moral issues. Two hundred and forty participants evaluated 24 moral and non-moral dilemmas either by judging ("Is it acceptable to…") or reporting the choice of action they would make ("Would you do…"). We also investigated the influence of varying the number of people benefiting from the decision and the closeness of relationship of the decision maker with the potential victim on these two types of decision. Variations in the number of beneficiaries from the decision did not influence judgment nor choice of action. By contrast, closeness of relationship with the victim had a greater influence on the choice of action than on judgment. This differentiation between evaluative judgments and choices of action argues in favor of each of them being supported by (at least partially) different psychological processes.


The relationship of metabolic syndrome and health-promoting lifestyle profiles of Latinos in the Northwest.
Latinos are at elevated risk for metabolic syndrome (MetS), a cluster of metabolic factors predictive of cardiovascular disease and diabetes. This study summarizes the association of MetS risk factors with self-reported health behaviors for 225 low-income, Northwest Latino men and women according to age and gender. The Health-Promoting Lifestyle Profile II (HPLP II) in English and Spanish was used to measure the extent to which participants engaged in health-promoting behavior. Biophysical measures included body composition, blood pressure, and fasting venous blood analysis. Men had significantly higher triglycerides, blood glucose, and systolic and diastolic blood pressure readings. Both men and women had central obesity measurements above the recommended cutoffs. There were no statistically significant differences except for physical activity on the HPLP II scores according to level of risk for MetS.


Examining the Minimal Important Difference of Patient-reported Outcome Measures for Individuals with Knee Osteoarthritis: A Model Using the Knee Injury and Osteoarthritis Outcome Score.
To examine the influence of different analytical methods, baseline covariates, followup periods, and anchor questions when establishing a minimal important difference (MID) for individuals with knee osteoarthritis (OA). Second, to propose MID for improving and worsening on the Knee injury and Osteoarthritis Outcome Score (KOOS). Retrospective analysis of prospectively collected data from 272 patients with knee OA undergoing a multidisciplinary nonsurgical management strategy. The magnitude and rate of change as well as the influence of baseline covariates were examined for 5 KOOS subscales over 52 weeks. The MID for improving and worsening were investigated using 4 anchor-based methods. Waitlisted for joint replacement and exhibiting unilateral/bilateral symptoms influenced change in KOOS over time. Generally, low correlations between anchors and KOOS change scores limited calculations of MID; thus, they were only proposed for the pain, activities of daily living, and quality of life subscales. The method used to calculate the MID influenced the cutpoint; however, the type of anchor question only influenced the MID when analyzed with a particular mean change method. Depending on patient and clinical characteristics, the subscale, and the analytical approach used, the MID for KOOS improvement ranged from an absolute change of -1.5 to 20.6 points and worsening ranged from -19.17 to 8.5 points. MID vary with patient and clinical characteristics, KOOS subscale, and analytical approach. Provided the anchor question is relevant to the patient-reported outcome and baseline status is considered, the anchor does not appear to influence the MID for improvement or worsening when using some anchor-based methods.